Posthodiplostomum cuticola (Digenea: Diplostomatidae) in intermediate fish hosts: factors contributing to the parasite infection and prey selection by the definitive bird host.

PubMed

Ondracková, M; Simková, A; Gelnar, M; Jurajda, P

2004-12-01

Infection parameters of Posthodiplostomum cuticola, a digenean parasite with a complex life-cycle, were investigated in fish (the second intermediate host) from 6 floodplain water bodies over 2 years. A broad range of factors related to abiotic characteristics of localities, density of the first intermediate (planorbid snails) and definitive (wading birds) hosts and fish community structure were tested for their effects on P. cuticola infection in juvenile and adult fish. Characters of the littoral zone and flood duration were found to be important factors for the presence of the first intermediate and definitive hosts. Visitation time of definitive bird hosts was also related to adult fish host density. Localities with P. cuticola infected fish were visited by a higher number of bird species. Infection of P. cuticola in fish and similarities in infection among fish host assemblages were correlated with fish host density and fish species composition. Parasite infection in both adult and juvenile fishes was associated with the slope of the bank and the bottom type, in particular in juvenile fish assemblages with snail host density. We conclude that habitat characteristics, snail host density and fish community structure contribute significantly to P. cuticola infection in fish hosts.

Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells

PubMed Central

Tilton, Susan C.; Menachery, Vineet D.; Gralinski, Lisa E.; Schäfer, Alexandra; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Chang, Jean; Luna, Maria L.; Long, Casey E.; Shukla, Anil K.; Bankhead, Armand R.; Burkett, Susan E.; Zornetzer, Gregory; Tseng, Chien-Te Kent; Metz, Thomas O.; Pickles, Raymond; McWeeney, Shannon; Smith, Richard D.; Katze, Michael G.; Waters, Katrina M.; Baric, Ralph S.

2013-01-01

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo. PMID:23365422

A Systematic Review of the Epidemiology of Echinococcosis in Domestic and Wild Animals

PubMed Central

Otero-Abad, Belen; Torgerson, Paul R.

2013-01-01

Background Human echinococcosis is a neglected zoonosis caused by parasites of the genus Echinococcus. The most frequent clinical forms of echinococcosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are responsible for a substantial health and economic burden, particularly to low-income societies. Quantitative epidemiology can provide important information to improve the understanding of parasite transmission and hence is an important part of efforts to control this disease. The purpose of this review is to give an insight on factors associated with echinococcosis in animal hosts by summarising significant results reported from epidemiological studies identified through a systematic search. Methodology and Principal Findings The systematic search was conducted mainly in electronic databases but a few additional records were obtained from other sources. Retrieved entries were examined in order to identify available peer-reviewed epidemiological studies that found significant risk factors for infection using associative statistical methods. One hundred studies met the eligibility criteria and were suitable for data extraction. Epidemiological factors associated with increased risk of E. granulosus infection in dogs included feeding with raw viscera, possibility of scavenging dead animals, lack of anthelmintic treatment and owners' poor health education and indicators of poverty. Key factors associated with E. granulosus infection in intermediate hosts were related to the hosts' age and the intensity of environmental contamination with parasite eggs. E. multilocularis transmission dynamics in animal hosts depended on the interaction of several ecological factors, such as hosts' population densities, host-prey interactions, landscape characteristics, climate conditions and human-related activities. Conclusions/Significance Results derived from epidemiological studies provide a better understanding of the behavioural, biological and ecological factors involved in the transmission of this parasite and hence can aid in the design of more effective control strategies. PMID:23755310

Effects of host injury on susceptibility of marine reef fishes to ectoparasitic gnathiid isopods

USGS Publications Warehouse

Jenkins, William G.; Demopoulos, Amanda W.J.; Sikkel, Paul C.

2018-01-01

The importance of the role that parasites play in ecological communities is becoming increasingly apparent. However much about their impact on hosts and thus populations and communities remains poorly understood. A common observation in wild populations is high variation in levels of parasite infestation among hosts. While high variation could be due to chance encounter, there is increasing evidence to suggest that such patterns are due to a combination of environmental, host, and parasite factors. In order to examine the role of host condition on parasite infection, rates of Gnathia marleyi infestation were compared between experimentally injured and uninjured fish hosts. Experimental injuries were similar to the minor wounds commonly observed in nature. The presence of the injury significantly increased the probability of infestation by gnathiids. However, the level of infestation (i.e., total number of gnathiid parasites) for individual hosts, appeared to be unaffected by the treatment. The results from this study indicate that injuries obtained by fish in nature may carry the additional cost of increased parasite burden along with the costs typically associated with physical injury. These results suggest that host condition may be an important factor in determining the likelihood of infestation by a common coral reef fish ectoparasite, G. marleyi.

Feeding preferences and performance of an aquatic lepidopteran on macrophytes: plant hosts as food and habitat.

PubMed

Dorn, Nathan J; Cronin, Greg; Lodge, David M

2001-08-01

Although host preferences in phytophagous insects may be generated by several factors, few studies have simultaneously examined several potential host choice determinants. In this study we tested the impact of the following potential host choice determinants on host preference of the semi-aquatic lepidopteran Munroessa gyralis (Pyralidae): growth on different host plants; protein content, polyphenolic content, toughness, and chemical extracts of different host plants; prior feeding experience; and predation pressure on the caterpillar by fishes. Two water lilies, Brasenia schreberi and Nymphaea odorata, were preferred in cafeteria-style feeding experiments over 14 other species of vascular plants. The most preferred water lily (Brasenia) also afforded the fastest growth relative to three other species on which growth was measured. Feeding preferences across species were unrelated to protein content, polyphenolic content, or toughness. Domiciles constructed by caterpillars from leaf fragments were protective from field assemblages of fishes, but domiciles made from preferred or unpreferred host species conferred no significant protection from fish in the laboratory. Caterpillars responded positively to chemical cues of water lilies, and prior feeding experience increased preference for an otherwise unpreferred water lily (Nuphar advena) within the life-span of individual caterpillars. M. gyralis is a generalist herbivore exhibiting modest preference induction and preferences for and among members of the family Nymphaeaceae. Our results suggest that relative growth rates, chemical cues, and previous feeding experience are important factors determining feeding preference. Protein content, polyphenolic content, and toughness appear less important, and the importance of fish predators remains in question. As pupation seems to occur exclusively on Nymphaea, we suggest that host use may be restricted due to life-stage-specific developmental constraints that are not apparent from the results of growth or preference assays. It is currently unknown how often specific life-stages may restrict host use, but our work suggests this as a potentially important area of inquiry.

Gut Microbiota and IGF-1.

PubMed

Yan, Jing; Charles, Julia F

2018-04-01

Microbiota and their hosts have coevolved for millions of years. Microbiota are not only critical for optimal development of the host under normal physiological growth, but also important to ensure proper host development during nutrient scarcity or disease conditions. A large body of research has begun to detail the mechanism(s) of how microbiota cooperate with the host to maintain optimal health status. One crucial host pathway recently demonstrated to be modulated by microbiota is that of the growth factor insulin like growth factor 1 (IGF-1). Gut microbiota are capable of dynamically modulating circulating IGF-1 in the host, with the majority of data suggesting that microbiota induce host IGF-1 synthesis to influence growth. Microbiota-derived metabolites such as short chain fatty acids are sufficient to induce IGF-1. Whether microbiota induction of IGF-1 is mediated by the difference in growth hormone expression or the host sensitivity to growth hormone is still under investigation. This review summarizes the current data detailing the interaction between gut microbiota, IGF-1 and host development.

Unravelling mummies: cryptic diversity, host specificity, trophic and coevolutionary interactions in psyllid - parasitoid food webs.

PubMed

Hall, Aidan A G; Steinbauer, Martin J; Taylor, Gary S; Johnson, Scott N; Cook, James M; Riegler, Markus

2017-06-06

Parasitoids are hyperdiverse and can contain morphologically and functionally cryptic species, making them challenging to study. Parasitoid speciation can arise from specialisation on niches or diverging hosts. However, which process dominates is unclear because cospeciation across multiple parasitoid and host species has rarely been tested. Host specificity and trophic interactions of the parasitoids of psyllids (Hemiptera) remain mostly unknown, but these factors are fundamentally important for understanding of species diversity, and have important applied implications for biological control. We sampled diverse parasitoid communities from eight Eucalyptus-feeding psyllid species in the genera Cardiaspina and Spondyliaspis, and characterised their phylogenetic and trophic relationships using a novel approach that forensically linked emerging parasitoids with the presence of their DNA in post-emergence insect mummies. We also tested whether parasitoids have cospeciated with their psyllid hosts. The parasitoid communities included three Psyllaephagus morphospecies (two primary and, unexpectedly, one heteronomous hyperparasitoid that uses different host species for male and female development), and the hyperparasitoid, Coccidoctonus psyllae. However, the number of genetically delimited Psyllaephagus species was three times higher than the number of recognisable morphospecies, while the hyperparasitoid formed a single generalist species. In spite of this, cophylogenetic analysis revealed unprecedented codivergence of this hyperparasitoid with its primary parasitoid host, suggesting that this single hyperparasitoid species is possibly diverging into host-specific species. Overall, parasitoid and hyperparasitoid diversification was characterised by functional conservation of morphospecies, high host specificity and some host switching between sympatric psyllid hosts. We conclude that host specialisation, host codivergence and host switching are important factors driving the species diversity of endoparasitoid communities of specialist host herbivores. Specialisation in parasitoids can also result in heteronomous life histories that may be more common than appreciated. A host generalist strategy may be rare in endoparasitoids of specialist herbivores despite the high conservation of morphology and trophic roles, and endoparasitoid species richness is likely to be much higher than previously estimated. This also implies that the success of biological control requires detailed investigation to enable accurate identification of parasitoid-host interactions before candidate parasitoid species are selected as biological control agents for target pests.

Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

EPA Science Inventory

Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host ...

Helminth communities of four commercially important fish species from Chetumal Bay, Mexico.

PubMed

Aguirre-Macedo, M L; Vidal-Martínez, V M; González-Solís, D; Caballero, P I

2007-03-01

The relative importance of ecology and evolution as factors determining species richness and composition of the helminth communities of fish is a matter of current debate. Theoretical studies use host-parasite lists, but these do not include studies on a temporal or spatial scale. Local environmental conditions and host biological characteristics are shown to influence helminth species richness and composition in four fish species (Eugerres plumieri, Hexanematichthys assimilis, Oligoplites saurus, and Scomberomorus maculatus) in Chetumal Bay, Mexico. With the exception of H. assimilis, the helminth communities had not been previously studied and possible associations between environmental and host biological characteristics as factors determining helminth species richness and composition using redundancy analysis (RDA) are described. Thirty-four helminth species are identified, with the highest number of species (19 total (mean = 6.3 +/- 2.1)) and the lowest (9 (4.0 +/- 1.0)) occurring in H. assimilis and S. maculatus, respectively. The larval nematodes Contracaecum sp. and Pseudoterranova sp. were not only the helminth species shared by all four host species but also were the most prevalent and abundant. Statistical associations between helminth community parameters and local ecological variables such as host habitat use, feeding habits, mobility, and time of residence in coastal lagoons are identified. Phylogeny is important because it clearly separates all four host species by their specialist parasites, although specific habitat and feeding habits also significantly influence the differentiation between the four fish species.

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

PubMed Central

Johnson, Timothy J.; Ricke, Steven C.; Nayak, Rajesh; Danzeisen, Jessica

2013-01-01

SUMMARY Enteric pathogens such as Salmonella enterica cause significant morbidity and mortality. S. enterica serovars are a diverse group of pathogens that have evolved to survive in a wide range of environments and across multiple hosts. S. enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a restricted host range, in which they are typically associated with one or a few host species, while S. Enteritidis and S. Typhimurium have broad host ranges. This review examines how S. enterica has evolved through adaptation to different host environments, especially as related to the chicken host, and continues to be an important human pathogen. Several factors impact host range, and these include the acquisition of genes via horizontal gene transfer with plasmids, transposons, and phages, which can potentially expand host range, and the loss of genes or their function, which would reduce the range of hosts that the organism can infect. S. Gallinarum, with a limited host range, has a large number of pseudogenes in its genome compared to broader-host-range serovars. S. enterica serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may help them colonize poultry more efficiently. The ability to colonize different hosts also involves interactions with the host's immune system and commensal organisms that are present. Thus, the factors that impact the ability of Salmonella to colonize a particular host species, such as chickens, are complex and multifactorial, involving the host, the pathogen, and extrinsic pressures. It is the interplay of these factors which leads to the differences in host ranges that we observe today. PMID:24296573

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

PubMed

Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-07-29

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

Intracellular Trafficking and Persistence of Acinetobacter baumannii Requires Transcription Factor EB

PubMed Central

Parra-Millán, Raquel; Guerrero-Gómez, David; Ayerbe-Algaba, Rafael; Pachón-Ibáñez, Maria Eugenia; Miranda-Vizuete, Antonio

2018-01-01

ABSTRACT Acinetobacter baumannii is a significant human pathogen associated with hospital-acquired infections. While adhesion, an initial and important step in A. baumannii infection, is well characterized, the intracellular trafficking of this pathogen inside host cells remains poorly studied. Here, we demonstrate that transcription factor EB (TFEB) is activated after A. baumannii infection of human lung epithelial cells (A549). We also show that TFEB is required for the invasion and persistence inside A549 cells. Consequently, lysosomal biogenesis and autophagy activation were observed after TFEB activation which could increase the death of A549 cells. In addition, using the Caenorhabditis elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. These results identify TFEB as a conserved key factor in the pathogenesis of A. baumannii. IMPORTANCE Adhesion is an initial and important step in Acinetobacter baumannii infections. However, the mechanism of entrance and persistence inside host cells is unclear and remains to be understood. In this study, we report that, in addition to its known role in host defense against Gram-positive bacterial infection, TFEB also plays an important role in the intracellular trafficking of A. baumannii in host cells. TFEB was activated shortly after A. baumannii infection and is required for its persistence within host cells. Additionally, using the C. elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. PMID:29600279

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

The effect of water contamination and host-related factors on ectoparasite load in an insectivorous bat.

PubMed

Korine, Carmi; Pilosof, Shai; Gross, Amit; Morales-Malacara, Juan B; Krasnov, Boris R

2017-09-01

We examined the effects of sex, age, and reproductive state of the insectivorous bat Pipistrellus kuhlii on the abundance and prevalence of arthropod ectoparasites (Macronyssidae and Cimicidae) in habitats with either sewage-polluted or natural bodies of water, in the Negev Desert, Israel. We chose water pollution as an environmental factor because of the importance of water availability in desert environments, particularly for P. kuhlii, which needs to drink on a daily basis. We predicted that parasite infestation rates would be affected by both environment and demographic cohort of the host. We found that female bats in the polluted site harbored significantly more mites than female bats in the natural site and that juveniles in the polluted site harbored significantly more cimicid individuals than juveniles in the natural site. We further found that age and sex (host-related factors) affected ectoparasite prevalence and intensity (i.e., the abundance of parasites) in the polluted site. Our results may suggest that the interaction between host-related and environment-related factors affected parasite infestations, with females and young bats being more susceptible to ectoparasites when foraging over polluted water. This effect may be particularly important for bats that must drink or forage above water for other wildlife that depend on drinking water for survival.

Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors

PubMed Central

Garchitorena, Andrés; Guégan, Jean-François; Léger, Lucas; Eyangoh, Sara; Marsollier, Laurent; Roche, Benjamin

2015-01-01

Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors. DOI: http://dx.doi.org/10.7554/eLife.07616.001 PMID:26216042

INTEGRATING PARASITES AND PATHOGENS INTO THE STUDY OF GEOGRAPHIC RANGE LIMITS.

PubMed

Bozick, Brooke A; Real, Leslie A

2015-12-01

The geographic distributions of all species are limited, and the determining factors that set these limits are of fundamental importance to the fields of ecology and evolutionary biology. Plant and animal ranges have been of primary concern, while those of parasites, which represent much of the Earth's biodiversity, have been neglected. Here, we review the determinants of the geographic ranges of parasites and pathogens, and explore how parasites provide novel systems with which to investigate the ecological and evolutionary processes governing host/parasite spatial distributions. Although there is significant overlap in the causative factors that determine range borders of parasites and free-living species, parasite distributions are additionally constrained by the geographic range and ecology of the host species' population, as well as by evolutionary factors that promote host-parasite coevolution. Recently, parasites have been used to infer population demographic and ecological information about their host organisms and we conclude that this strategy can be further exploited to understand geographic range limitations of both host and parasite populations.

Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

PubMed Central

Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

1995-01-01

Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation. Images Fig. 2 PMID:11607567

Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

PubMed

Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

1995-08-01

Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

Emerging and re-emerging infections.

PubMed

Lim, V K

1999-06-01

An emerging infection is defined as an infection which has newly appeared in a population while a re-emerging infection is one which has existed in the past but its incidence is rapidly increasing. The reasons for the emergence and re-emergence of infections are not well understood but appear to be associated with factors that involve the pathogen, the host and the environment. These factors are often inter-related and act together in a complex manner to bring about changes in patterns of infection. Pathogens are extremely resourceful and possess mechanisms to adapt to new hosts and environments as well as to acquire new virulence traits. Host factors include herd immunity, social behaviour and demographics. Environmental factors like the climate, deforestation and new technologies have an impact on the emergence of infections. The challenge is to contain an infection when it emerges but more importantly to prevent its emergence in the first place. As the emergence of an infection is complex and multifactorial, a multidisciplinary approach is required. Health based strategies alone are insufficient. Social, economic and environmental measures and the political will to implement appropriate policies are equally important.

Spatial and temporal distribution of the vibrionaceae in coastal waters of Hawaii, Australia, and France.

PubMed

Jones, B W; Maruyama, A; Ouverney, C C; Nishiguchi, M K

2007-08-01

Relatively little is known about large-scale spatial and temporal fluctuations in bacterioplankton, especially within the bacterial families. In general, however, a number of abiotic factors (namely, nutrients and temperature) appear to influence distribution. Community dynamics within the Vibrionaceae are of particular interest to biologists because this family contains a number of important pathogenic, commensal, and mutualist species. Of special interest to this study is the mutualism between sepiolid squids and Vibrio fischeri and Vibrio logei, where host squids seed surrounding waters daily with their bacterial partners. This study seeks to examine the spatial and temporal distribution of the Vibrionaceae with respect to V. fischeri and V. logei in Hawaii, southeastern Australia, and southern France sampling sites. In particular, we examine how the presence of sepiolid squid hosts influences community population structure within the Vibrionaceae. We found that abiotic (temperature) and biotic (host distribution) factors both influence population dynamics. In Hawaii, three sites within squid host habitat contained communities of Vibrionaceae with higher proportions of V. fischeri. In Australia, V. fischeri numbers at host collection sites were greater than other populations; however, there were no spatial or temporal patterns seen at other sample sites. In France, host presence did not appear to influence Vibrio communities, although sampled populations were significantly greater in the winter than summer sampling periods. Results of this study demonstrate the importance of understanding how both abiotic and biotic factors interact to influence bacterial community structure within the Vibrionaceae.

Altering host resistance to infections through microbial transplantation.

PubMed

Willing, Benjamin P; Vacharaksa, Anjalee; Croxen, Matthew; Thanachayanont, Teerawat; Finlay, B Brett

2011-01-01

Host resistance to bacterial infections is thought to be dictated by host genetic factors. Infections by the natural murine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections) vary between mice strains, from mild self-resolving colonization in NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component had been shown to be responsible for the differences observed with C. rodentium infections. Because the intestinal microbiota is important in regulating resistance to infection, and microbial composition is dependent on host genotype, it was tested whether variations in microbial composition between mouse strains contributed to differences in "host" susceptibility by transferring the microbiota of resistant mice to lethally susceptible mice prior to infection. Successful transfer of the microbiota from resistant to susceptible mice resulted in delayed pathogen colonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptides Reg3γ and Reg3β, and immunono-neutralization of IL-22 abrogated the beneficial effect of microbiota transfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importance of the microbiota and how it regulates mucosal immunity, providing an important factor in susceptibility to enteric infection. Transfer of resistance through microbial transplantation (bacteriotherapy) provides additional mechanisms to alter "host" resistance, and a novel means to alter enteric infection and to study host-pathogen interactions.

Review of the trematode genus Ribeiroia (Psilostomidae): ecology, life history and pathogenesis with special emphasis on the amphibian malformation problem.

PubMed

Johnson, Pieter T J; Sutherland, Daniel R; Kinsella, J M; Lunde, Kevin B

2004-01-01

Trematodes in the genus Ribeiroia have an indirect life cycle involving planorbid snails as first intermediate hosts, fishes or amphibians as second intermediate hosts and birds or mammals as definitive hosts. Although rarely pathogenic in definitive hosts, Ribeiroia infection can cause severe pathology and mortality in snails and amphibians. This group of parasites has gained notoriety for its prominent rol in the recent rash of amphibian deformities in North America. Under some circumstances, these malformations may enhance parasite transmission by rendering infected amphibian hosts more susceptible to definitive host predators. However, increasing reports of malformations in North American amphibian populations emphasize the importance of understanding infection patterns. Here we review important aspects of the biology, ecology, life cycle and pathogenesis of parasites in the genus Ribeiroia and identify priorities for future research. Based on available morphological descriptions and preliminary molecular data, three species of Ribeiroia are recognized: R. ondatrae in the Americas, R. marini in the Caribbean and R. congolensis/C. lileta in Africa. We further evaluate the influence of abiotic and biotic factors in determining the intensity and prevalence of Ribeiroia infection and malformations in amphibians, highlighting the importance of habitat alteration and secondary factors (e.g. aquatic eutrophication, contaminants) in promoting infection. Although not a "new" parasite, Ribeiroia may have increased in range, prevalence, or intensity in recent years, particularly within amphibian hosts. Nevertheless, while much is known about this intriguing group of parasites, there remains much that we do not know. Particular importance for future research is placed on the following areas: evaluating the phylogenetic position of the genus, establishing the molecular mechanism of parasite-induced malformations in amphibians, isolating the drivers of parasite transmission under field conditions and studying the consequences of malformations for parasite and host populations. Investigation of these questions will benefit enormously from a multidisciplinary approach that effectively integrates parasitology, developmental biology, immunology, herpetology and aquatic ecology.

Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria

PubMed Central

Kendjo, Eric; Augé-Courtoi, Claire; Cojean, Sandrine; Clain, Jérôme; Houzé, Pascal; Thellier, Marc; Hubert, Veronique; Deloron, Philippe; Houzé, Sandrine

2017-01-01

Objectives Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known. Methods From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology) associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants). Results Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host. Conclusions Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden. PMID:28410415

Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions.

PubMed

Duneau, David; Luijckx, Pepijn; Ben-Ami, Frida; Laforsch, Christian; Ebert, Dieter

2011-02-22

Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different steps can explain different aspects of the coevolutionary dynamics of the system: the properties of the attachment step, explaining the rapid evolution of infectivity and the properties of later parasite proliferation explaining the evolution of virulence. Our study underlines the importance of resolving the infection process in order to better understand host-parasite interactions.

Ecophysiology meets conservation: understanding the role of disease in amphibian population declines

PubMed Central

Blaustein, Andrew R.; Gervasi, Stephanie S.; Johnson, Pieter T. J.; Hoverman, Jason T.; Belden, Lisa K.; Bradley, Paul W.; Xie, Gisselle Y.

2012-01-01

Infectious diseases are intimately associated with the dynamics of biodiversity. However, the role that infectious disease plays within ecological communities is complex. The complex effects of infectious disease at the scale of communities and ecosystems are driven by the interaction between host and pathogen. Whether or not a given host–pathogen interaction results in progression from infection to disease is largely dependent on the physiological characteristics of the host within the context of the external environment. Here, we highlight the importance of understanding the outcome of infection and disease in the context of host ecophysiology using amphibians as a model system. Amphibians are ideal for such a discussion because many of their populations are experiencing declines and extinctions, with disease as an important factor implicated in many declines and extinctions. Exposure to pathogens and the host's responses to infection can be influenced by many factors related to physiology such as host life history, immunology, endocrinology, resource acquisition, behaviour and changing climates. In our review, we discuss the relationship between disease and biodiversity. We highlight the dynamics of three amphibian host–pathogen systems that induce different effects on hosts and life stages and illustrate the complexity of amphibian–host–parasite systems. We then review links between environmental stress, endocrine–immune interactions, disease and climate change. PMID:22566676

Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands.

PubMed

Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A; van der Linden, Giel T J; Schaminée, Joop H J; Siepel, Henk; Kleijn, David

2014-12-09

Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species.

Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands

PubMed Central

Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A.; van der Linden, Giel T. J.; Schaminée, Joop H. J.; Siepel, Henk; Kleijn, David

2014-01-01

Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species. PMID:25422416

ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vieira da Silva, Claudio; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sao Paulo, Rua Botucatu, 862, 6o andar, 04023-062 Sao Paulo, SP; Alves da Silva, Erika

2009-01-16

Toxoplasma gondii infects a variety of different cell types in a range of different hosts. Host cell invasion by T. gondii occurs by active penetration of the host cell, a process previously described as independent of host actin polymerization. Also, the parasitophorous vacuole has been shown to resist fusion with endocytic and exocytic pathways of the host cell. ADP-ribosylation factor-6 (ARF6) belongs to the ARF family of small GTP-binding proteins. ARF6 regulates membrane trafficking and actin cytoskeleton rearrangements at the plasma membrane. Here, we have observed that ARF6 is recruited to the parasitophorous vacuole of tachyzoites of T. gondii RHmore » strain and it also plays an important role in the parasite cell invasion with activation of PI3-kinase and recruitment of PIP{sub 2} and PIP{sub 3} to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.« less

Interhost dispersal alters microbiome assembly and can overwhelm host innate immunity in an experimental zebrafish model.

PubMed

Burns, Adam R; Miller, Elizabeth; Agarwal, Meghna; Rolig, Annah S; Milligan-Myhre, Kathryn; Seredick, Steve; Guillemin, Karen; Bohannan, Brendan J M

2017-10-17

The diverse collections of microorganisms associated with humans and other animals, collectively referred to as their "microbiome," are critical for host health, but the mechanisms that govern their assembly are poorly understood. This has made it difficult to identify consistent host factors that explain variation in microbiomes across hosts, despite large-scale sampling efforts. While ecological theory predicts that the movement, or dispersal, of individuals can have profound and predictable consequences on community assembly, its role in the assembly of animal-associated microbiomes remains underexplored. Here, we show that dispersal of microorganisms among hosts can contribute substantially to microbiome variation, and is able to overwhelm the effects of individual host factors, in an experimental test of ecological theory. We manipulated dispersal among wild-type and immune-deficient myd88 knockout zebrafish and observed that interhost dispersal had a large effect on the diversity and composition of intestinal microbiomes. Interhost dispersal was strong enough to overwhelm the effects of host factors, largely eliminating differences between wild-type and immune-deficient hosts, regardless of whether dispersal occurred within or between genotypes, suggesting dispersal can independently alter the ecology of microbiomes. Our observations are consistent with a predictive model that assumes metacommunity dynamics and are likely mediated by dispersal-related microbial traits. These results illustrate the importance of microbial dispersal to animal microbiomes and motivate its integration into the study of host-microbe systems.

Influenza A Virus Dysregulates Host Histone Deacetylase 1 That Inhibits Viral Infection in Lung Epithelial Cells

PubMed Central

Nagesh, Prashanth Thevkar

2016-01-01

ABSTRACT Viruses dysregulate the host factors that inhibit virus infection. Here, we demonstrate that human enzyme, histone deacetylase 1 (HDAC1) is a new class of host factor that inhibits influenza A virus (IAV) infection, and IAV dysregulates HDAC1 to efficiently replicate in epithelial cells. A time-dependent decrease in HDAC1 polypeptide level was observed in IAV-infected cells, reducing to <50% by 24 h of infection. A further depletion (97%) of HDAC1 expression by RNA interference increased the IAV growth kinetics, increasing it by >3-fold by 24 h and by >6-fold by 48 h of infection. Conversely, overexpression of HDAC1 decreased the IAV infection by >2-fold. Likewise, a time-dependent decrease in HDAC1 activity, albeit with slightly different kinetics to HDAC1 polypeptide reduction, was observed in infected cells. Nevertheless, a further inhibition of deacetylase activity increased IAV infection in a dose-dependent manner. HDAC1 is an important host deacetylase and, in addition to its role as a transcription repressor, HDAC1 has been lately described as a coactivator of type I interferon response. Consistent with this property, we found that inhibition of deacetylase activity either decreased or abolished the phosphorylation of signal transducer and activator of transcription I (STAT1) and expression of interferon-stimulated genes, IFITM3, ISG15, and viperin in IAV-infected cells. Furthermore, the knockdown of HDAC1 expression in infected cells decreased viperin expression by 58% and, conversely, the overexpression of HDAC1 increased it by 55%, indicating that HDAC1 is a component of IAV-induced host type I interferon antiviral response. IMPORTANCE Influenza A virus (IAV) continues to significantly impact global public health by causing regular seasonal epidemics, occasional pandemics, and zoonotic outbreaks. IAV is among the successful human viral pathogens that has evolved various strategies to evade host defenses, prevent the development of a universal vaccine, and acquire antiviral drug resistance. A comprehensive knowledge of IAV-host interactions is needed to develop a novel and alternative anti-IAV strategy. Host produces a variety of factors that are able to fight IAV infection by employing various mechanisms. However, the full repertoire of anti-IAV host factors and their antiviral mechanisms has yet to be identified. We have identified here a new host factor, histone deacetylase 1 (HDAC1) that inhibits IAV infection. We demonstrate that HDAC1 is a component of host innate antiviral response against IAV, and IAV undermines HDAC1 to limit its role in antiviral response. PMID:26912629

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

PubMed Central

Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-01-01

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

Benefits of fidelity: does host specialization impact nematode parasite life history and fecundity?

PubMed

Koprivnikar, J; Randhawa, H S

2013-04-01

The range of hosts used by a parasite is influenced by macro-evolutionary processes (host switching, host-parasite co-evolution), as well as 'encounter filters' and 'compatibility filters' at the micro-evolutionary level driven by host/parasite ecology and physiology. Host specialization is hypothesized to result in trade-offs with aspects of parasite life history (e.g. reproductive output), but these have not been well studied. We used previously published data to create models examining general relationships among host specificity and important aspects of life history and reproduction for nematodes parasitizing animals. Our results indicate no general trade-off between host specificity and the average pre-patent period (time to first reproduction), female size, egg size, or fecundity of these nematodes. However, female size was positively related to egg size, fecundity, and pre-patent period. Host compatibility may thus not be the primary determinant of specificity in these parasitic nematodes if there are few apparent trade-offs with reproduction, but rather, the encounter opportunities for new host species at the micro-evolutionary level, and other processes at the macro-evolutionary level (i.e. phylogeny). Because host specificity is recognized as a key factor determining the spread of parasitic diseases understanding factors limiting host use are essential to predict future changes in parasite range and occurrence.

Cytokines and their STATs in cutaneous and visceral leishmaniasis.

PubMed

Cummings, Hannah E; Tuladhar, Rashmi; Satoskar, Abhay R

2010-01-01

Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis.

Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance.

PubMed

Yildirim, Suleyman; Yeoman, Carl J; Janga, Sarath Chandra; Thomas, Susan M; Ho, Mengfei; Leigh, Steven R; White, Bryan A; Wilson, Brenda A; Stumpf, Rebecca M

2014-12-01

Bacterial communities colonizing the reproductive tracts of primates (including humans) impact the health, survival and fitness of the host, and thereby the evolution of the host species. Despite their importance, we currently have a poor understanding of primate microbiomes. The composition and structure of microbial communities vary considerably depending on the host and environmental factors. We conducted comparative analyses of the primate vaginal microbiome using pyrosequencing of the 16S rRNA genes of a phylogenetically broad range of primates to test for factors affecting the diversity of primate vaginal ecosystems. The nine primate species included: humans (Homo sapiens), yellow baboons (Papio cynocephalus), olive baboons (Papio anubis), lemurs (Propithecus diadema), howler monkeys (Alouatta pigra), red colobus (Piliocolobus rufomitratus), vervets (Chlorocebus aethiops), mangabeys (Cercocebus atys) and chimpanzees (Pan troglodytes). Our results indicated that all primates exhibited host-specific vaginal microbiota and that humans were distinct from other primates in both microbiome composition and diversity. In contrast to the gut microbiome, the vaginal microbiome showed limited congruence with host phylogeny, and neither captivity nor diet elicited substantial effects on the vaginal microbiomes of primates. Permutational multivariate analysis of variance and Wilcoxon tests revealed correlations among vaginal microbiota and host species-specific socioecological factors, particularly related to sexuality, including: female promiscuity, baculum length, gestation time, mating group size and neonatal birth weight. The proportion of unclassified taxa observed in nonhuman primate samples increased with phylogenetic distance from humans, indicative of the existence of previously unrecognized microbial taxa. These findings contribute to our understanding of host-microbe variation and coevolution, microbial biogeography, and disease risk, and have important implications for the use of animal models in studies of human sexual and reproductive diseases.

Host Genotype and Microbiota Contribute Asymmetrically to Transcriptional Variation in the Threespine Stickleback Gut

PubMed Central

Small, Clayton M.; Milligan-Myhre, Kathryn; Bassham, Susan; Guillemin, Karen

2017-01-01

Recent studies of interactions between hosts and their resident microbes have revealed important ecological and evolutionary consequences that emerge from these complex interspecies relationships, including diseases that occur when the interactions go awry. Given the preponderance of these interactions, we hypothesized that effects of the microbiota on gene expression in the developing gut—an important aspect of host biology—would be pervasive, and that these effects would be both comparable in magnitude to and contingent on effects of the host genetic background. To evaluate the effects of the microbiota, host genotype, and their interaction on gene expression in the gut of a genetically diverse, gnotobiotic host model, the threespine stickleback (Gasterosteus aculeatus), we compared RNA-seq data among 84 larval fish. Surprisingly, we found that stickleback population and family differences explained substantially more gene expression variation than the presence of microbes. Expression levels of 72 genes, however, were affected by our microbiota treatment. These genes, including many associated with innate immunity, comprise a tractable subset of host genetic factors for precise, systems-level study of host–microbe interactions in the future. Importantly, our data also suggest subtle signatures of a statistical interaction between host genotype and the microbiota on expression patterns of genetic pathways associated with innate immunity, coagulation and complement cascades, focal adhesion, cancer, and peroxisomes. These genotype-by-environment interactions may prove to be important leads to the understanding of host genetic mechanisms commonly at the root of sometimes complex molecular relationships between hosts and their resident microbes. PMID:28391321

Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut

PubMed Central

Reese, Aspen T; Cho, Eugenia H; Klitzman, Bruce; Nichols, Scott P; Wisniewski, Natalie A; Villa, Max M; Durand, Heather K; Jiang, Sharon; Midani, Firas S; Nimmagadda, Sai N; O'Connell, Thomas M; Wright, Justin P; Deshusses, Marc A

2018-01-01

How host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession. We showed gut redox potential increased within hours of an antibiotic dose in mice. Host and microbial functioning changed under treatment, but shifts in redox potentials could be attributed specifically to bacterial suppression in a host-free ex vivo human gut microbiota model. Redox dynamics were linked to blooms of the bacterial family Enterobacteriaceae. Ecological succession to pre-treatment composition was associated with recovery of gut redox, but also required dispersal from unaffected gut communities. As bacterial competition for electron acceptors can be a key ecological factor structuring gut communities, these results support the potential for manipulating gut microbiota through managing bacterial respiration. PMID:29916366

Impact of Leishmania Infection on Host Macrophage Nuclear Physiology and Nucleopore Complex Integrity

PubMed Central

Isnard, Amandine; Christian, Jan G.; Kodiha, Mohamed; Stochaj, Ursula; McMaster, W. Robert; Olivier, Martin

2015-01-01

The protease GP63 is an important virulence factor of Leishmania parasites. We previously showed that GP63 reaches the perinuclear area of host macrophages and that it directly modifies nuclear translocation of the transcription factors NF-κB and AP-1. Here we describe for the first time, using molecular biology and in-depth proteomic analyses, that GP63 alters the host macrophage nuclear envelope, and impacts on nuclear processes. Our results suggest that GP63 does not appear to use a classical nuclear localization signal common between Leishmania species for import, but degrades nucleoporins, and is responsible for nuclear transport alterations. In the nucleoplasm, GP63 activity accounts for the degradation and mislocalization of proteins involved amongst others in gene expression and in translation. Collectively, our data indicates that Leishmania infection strongly affects nuclear physiology, suggesting that targeting of nuclear physiology may be a strategy beneficial for virulent Leishmania parasites. PMID:25826301

Current concepts on the pathogenesis of Escherichia coli meningitis: implications for therapy and prevention.

PubMed

Kim, Kwang S

2012-06-01

Neonatal Escherichia coli meningitis continues to be an important cause of mortality and morbidity throughout the world. The major contributing factors to this mortality and morbidity include our incomplete knowledge on its pathogenesis and an emergence of antimicrobial-resistant E. coli. Recent reports of neonatal meningitis caused by E. coli producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge, and innovative approaches are needed to identify potential targets for prevention and therapy of E. coli meningitis. E. coli invasion of the blood-brain barrier is a prerequisite for penetration into the brain and requires specific microbial-host factors as well as microbe-specific and host-specific signaling molecules. Recent studies identified additional microbial and host factors contributing to E. coli invasion of the blood-brain barrier and elucidated their underlying mechanisms. Blockade of the microbial-host factors contributing to E. coli invasion of the blood-brain barrier was shown to be efficient in preventing E. coli penetration into the brain. Continued investigation on the microbial-host factors contributing to E. coli invasion of the blood-brain barrier is needed to identify new targets for prevention and therapy of E. coli meningitis, thereby limiting the exposure to emerging antimicrobial-resistant E. coli.

A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins

PubMed Central

de Wilde, Adriaan H.; Wannee, Kazimier F.; Scholte, Florine E. M.; Goeman, Jelle J.; ten Dijke, Peter; Snijder, Eric J.

2015-01-01

ABSTRACT To identify host factors relevant for severe acute respiratory syndrome-coronavirus (SARS-CoV) replication, we performed a small interfering RNA (siRNA) library screen targeting the human kinome. Protein kinases are key regulators of many cellular functions, and the systematic knockdown of their expression should provide a broad perspective on factors and pathways promoting or antagonizing coronavirus replication. In addition to 40 proteins that promote SARS-CoV replication, our study identified 90 factors exhibiting an antiviral effect. Pathway analysis grouped subsets of these factors in specific cellular processes, including the innate immune response and the metabolism of complex lipids, which appear to play a role in SARS-CoV infection. Several factors were selected for in-depth validation in follow-up experiments. In cells depleted for the β2 subunit of the coatomer protein complex (COPB2), the strongest proviral hit, we observed reduced SARS-CoV protein expression and a >2-log reduction in virus yield. Knockdown of the COPB2-related proteins COPB1 and Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) also suggested that COPI-coated vesicles and/or the early secretory pathway are important for SARS-CoV replication. Depletion of the antiviral double-stranded RNA-activated protein kinase (PKR) enhanced virus replication in the primary screen, and validation experiments confirmed increased SARS-CoV protein expression and virus production upon PKR depletion. In addition, cyclin-dependent kinase 6 (CDK6) was identified as a novel antiviral host factor in SARS-CoV replication. The inventory of pro- and antiviral host factors and pathways described here substantiates and expands our understanding of SARS-CoV replication and may contribute to the identification of novel targets for antiviral therapy. IMPORTANCE Replication of all viruses, including SARS-CoV, depends on and is influenced by cellular pathways. Although substantial progress has been made in dissecting the coronavirus replicative cycle, our understanding of the host factors that stimulate (proviral factors) or restrict (antiviral factors) infection remains far from complete. To study the role of host proteins in SARS-CoV infection, we set out to systematically identify kinase-regulated processes that influence virus replication. Protein kinases are key regulators in signal transduction, controlling a wide variety of cellular processes, and many of them are targets of approved drugs and other compounds. Our screen identified a variety of hits and will form the basis for more detailed follow-up studies that should contribute to a better understanding of SARS-CoV replication and coronavirus-host interactions in general. The identified factors could be interesting targets for the development of host-directed antiviral therapy to treat infections with SARS-CoV or other pathogenic coronaviruses. PMID:26041291

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; McCoy, Kathy D; Wullaert, Andy

2018-04-19

Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome.

PubMed

Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Liu, Zhen-Xing; Hao, Le; Ma, Jiang-Yao; Li, Yu-Gu

2016-02-24

Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.

Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome

PubMed Central

Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Liu, Zhen-Xing; Hao, Le; Ma, Jiang-Yao; Li, Yu-Gu

2016-01-01

Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts. PMID:26927064

Virulence Factors of Helicobacter pylori: A Review

PubMed Central

Roesler, Bruna M.; Rabelo-Gonçalves, Elizabeth M.A.; Zeitune, José M.R.

2014-01-01

Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome. PMID:24833944

Host mitochondrial association evolved in the human parasite Toxoplasma gondii via neofunctionalization of a gene duplicate

USDA-ARS?s Scientific Manuscript database

In Toxoplasma gondii, an intracellular parasite of humans and other warm-blooded animals, the ability to associate with host mitochondria (HMA) is driven by a locally expanded gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. The importance of copy number in the e...

Reduced taxonomic richness of lice (Insecta: Phthiraptera) in diving birds.

PubMed

Felsõ, B; Rózsa, L

2006-08-01

Avian lice occupy different habitats in the host plumage that the physical environment outside the host body may affect in several ways. Interactions between host plumage and water may be an important source of such effects. Here, we use a comparative approach to examine the effect of a host's diving behavior on the taxonomic richness of its lice. Louse genera richness was significantly lower in clades of diving birds than on their nondiving sister clades. Species richness of host and body mass did not differ significantly between these clades; thus, these factors did not bias our results. This study suggests that the hosts' diving behavior can effectively influence ectoparasite communities.

Impact of sex on prognostic host factors in surgical patients with lung cancer.

PubMed

Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin

2017-12-01

Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.

Risk factors for community-acquired bacterial meningitis.

PubMed

Lundbo, Lene Fogt; Benfield, Thomas

2017-06-01

Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

The specificity of host-bat fly interaction networks across vegetation and seasonal variation.

PubMed

Zarazúa-Carbajal, Mariana; Saldaña-Vázquez, Romeo A; Sandoval-Ruiz, César A; Stoner, Kathryn E; Benitez-Malvido, Julieta

2016-10-01

Vegetation type and seasonality promote changes in the species composition and abundance of parasite hosts. However, it is poorly known how these variables affect host-parasite interaction networks. This information is important to understand the dynamics of parasite-host relationships according to biotic and abiotic changes. We compared the specialization of host-bat fly interaction networks, as well as bat fly and host species composition between upland dry forest and riparian forest and between dry and rainy seasons in a tropical dry forest in Jalisco, Mexico. Bat flies were surveyed by direct collection from bats. Our results showed that host-bat fly interaction networks were more specialized in upland dry forest compared to riparian forest. Bat fly species composition was different between the dry and rainy seasons, while host species composition was different between upland dry forest and riparian forest. The higher specialization in upland dry forest could be related to the differences in bat host species composition and their respective roosting habits. Variation in the composition of bat fly species between dry and rainy seasons coincides with the seasonal shifts in their species richness. Our study confirms the high specialization of host-bat fly interactions and shows the importance of biotic and abiotic factors to understand the dynamics of parasite-host interactions.

Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions

PubMed Central

2011-01-01

Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different steps can explain different aspects of the coevolutionary dynamics of the system: the properties of the attachment step, explaining the rapid evolution of infectivity and the properties of later parasite proliferation explaining the evolution of virulence. Our study underlines the importance of resolving the infection process in order to better understand host-parasite interactions. PMID:21342515

Phenotypic plasticity in a complex world: interactive effects of food and temperature on fitness components of a seed beetle.

PubMed

Stillwell, R Craig; Wallin, William G; Hitchcock, Lisa J; Fox, Charles W

2007-08-01

Most studies of phenotypic plasticity investigate the effects of an individual environmental factor on organism phenotypes. However, organisms exist in an ecologically complex world where multiple environmental factors can interact to affect growth, development and life histories. Here, using a multifactorial experimental design, we examine the separate and interactive effects of two environmental factors, rearing host species (Vigna radiata, Vigna angularis and Vigna unguiculata) and temperature (20, 25, 30 and 35 degrees C), on growth and life history traits in two populations [Burkina Faso (BF) and South India (SI)] of the seed beetle, Callosobruchus maculatus. The two study populations of beetles responded differently to both rearing host and temperature. We also found a significant interaction between rearing host and temperature for body size, growth rate and female lifetime fecundity but not larval development time or larval survivorship. The interaction was most apparent for growth rate; the variance in growth rate among hosts increased with increasing temperature. However, the details of host differences differed between our two study populations; the degree to which V. unguiculata was a better host than V. angularis or V. radiata increased at higher temperatures for BF beetles, whereas the degree to which V. unguiculata was the worst host increased at higher temperatures for SI beetles. We also found that the heritabilities of body mass, growth rate and fecundity were similar among rearing hosts and temperatures, and that the cross-temperature genetic correlation was not affected by rearing host, suggesting that genetic architecture is generally stable across rearing conditions. The most important finding of our study is that multiple environmental factors can interact to affect organism growth, but the degree of interaction, and thus the degree of complexity of phenotypic plasticity, varies among traits and between populations.

Advanced Molecular Surveillance of Hepatitis C Virus

PubMed Central

Gonçalves Rossi, Livia Maria; Escobar-Gutierrez, Alejandro; Rahal, Paula

2015-01-01

Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted. PMID:25781918

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

PubMed

Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

2015-04-01

Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

Host structural carbohydrate induces vector transmission of a bacterial plant pathogen.

PubMed

Killiny, Nabil; Almeida, Rodrigo P P

2009-12-29

Many insect-borne pathogens have complex life histories because they must colonize both hosts and vectors for successful dissemination. In addition, the transition from host to vector environments may require changes in gene expression before the pathogen's departure from the host. Xylella fastidiosa is a xylem-limited plant-pathogenic bacterium transmitted by leafhopper vectors that causes diseases in a number of economically important plants. We hypothesized that factors of host origin, such as plant structural polysaccharides, are important in regulating X. fastidiosa gene expression and mediating vector transmission of this pathogen. The addition of pectin and glucan to a simple defined medium resulted in dramatic changes in X. fastidiosa's phenotype and gene-expression profile. Cells grown in the presence of pectin became more adhesive than in other media tested. In addition, the presence of pectin and glucan in media resulted in significant changes in the expression of several genes previously identified as important for X. fastidiosa's pathogenicity in plants. Furthermore, vector transmission of X. fastidiosa was induced in the presence of both polysaccharides. Our data show that host structural polysaccharides mediate gene regulation in X. fastidiosa, which results in phenotypic changes required for vector transmission. A better understanding of how vector-borne pathogens transition from host to vector, and vice versa, may lead to previously undiscovered disease-control strategies.

To feed or not to feed: plant factors located in the epidermis, mesophyll, and sieve elements influence pea aphid's ability to feed on legume species.

PubMed

Schwarzkopf, Alexander; Rosenberger, Daniel; Niebergall, Martin; Gershenzon, Jonathan; Kunert, Grit

2013-01-01

The pea aphid (Acyrthosiphon pisum Harris), a legume specialist, encompasses at least 11 genetically distinct sympatric host races. Each host race shows a preference for a certain legume species. Six pea aphid clones from three host races were used to localize plant factors influencing aphid probing and feeding behavior on four legume species. Aphid performance was tested by measuring survival and growth. The location of plant factors influencing aphid probing and feeding was determined using the electrical penetration graph (EPG) technique. Every aphid clone performed best on the plant species from which it was originally collected, as well as on Vicia faba. On other plant species, clones showed intermediate or poor performance. The most important plant factors influencing aphid probing and feeding behavior were localized in the epidermis and sieve elements. Repetitive puncturing of sieve elements might be relevant for establishing phloem feeding, since feeding periods appear nearly exclusively after these repetitive sieve element punctures. A combination of plant factors influences the behavior of pea aphid host races on different legume species and likely contributes to the maintenance of these races.

The Immune Interplay between the Host and the Pathogen in Aspergillus fumigatus Lung Infection

PubMed Central

Sales-Campos, Helioswilton; Tonani, Ludmilla; Cardoso, Cristina Ribeiro Barros; Kress, Márcia Regina Von Zeska

2013-01-01

The interplay between Aspergillus fumigatus and the host immune response in lung infection has been subject of studies over the last years due to its importance in immunocompromised patients. The multifactorial virulence factors of A. fumigatus are related to the fungus biological characteristics, for example, structure, ability to grow and adapt to high temperatures and stress conditions, besides capability of evading the immune system and causing damage to the host. In this context, the fungus recognition by the host innate immunity occurs when the pathogen disrupts the natural and chemical barriers followed by the activation of acquired immunity. It seems clear that a Th1 response has a protective role, whereas Th2 reactions are often associated with higher fungal burden, and Th17 response is still controversial. Furthermore, a fine regulation of the effector immunity is required to avoid excessive tissue damage associated with fungal clearance, and this role could be attributed to regulatory T cells. Finally, in this work we reviewed the aspects involved in the complex interplay between the host immune response and the pathogen virulence factors, highlighting the immunological issues and the importance of its better understanding to the development of novel therapeutic approaches for invasive lung aspergillosis. PMID:23984400

The influence of aphids (Myzus persicae) and pink lady beetle larvae (Coleomegilla maculata) on host plant preference of imported cabbageworm (Pieris rapae)

USDA-ARS?s Scientific Manuscript database

Oviposition decisions by herbivorous insects hinge on multiple factors; host plant quality, enemy free space, plant density, offspring performance, and competition for resources all which influence decisions by an ovipositing female. Here, we evaluate whether the presence of aphids (a competitor) or...

Environment-Dependent Guest Exchange in Supramolecular Hosts

PubMed Central

2015-01-01

Dynamic exchange of guest molecules, encapsulated in host assemblies, is a phenomenon in supramolecular chemistry that has important implications in several applications. While the mechanism of exchange in micellar assemblies has been previously investigated, the effect of host and guest environment upon the guest-exchange dynamics has received little attention, if any. In this paper, we study the guest-exchange mechanism in pH-sensitive nanogels along with pH-insensitive nanogels as a control. By systematically comparing the behavior of these nanogels, we show that size, concentration, and hydrophobicity can all play a critical role in guest-exchange dynamics. More importantly, these studies reveal that the dominant mechanism of guest exchange can intimately depend on environmental factors. PMID:25244305

Host Diet Affects the Morphology of Monarch Butterfly Parasites.

PubMed

Hoang, Kevin; Tao, Leiling; Hunter, Mark D; de Roode, Jacobus C

2017-06-01

Understanding host-parasite interactions is essential for ecological research, wildlife conservation, and health management. While most studies focus on numerical traits of parasite groups, such as changes in parasite load, less focus is placed on the traits of individual parasites such as parasite size and shape (parasite morphology). Parasite morphology has significant effects on parasite fitness such as initial colonization of hosts, avoidance of host immune defenses, and the availability of resources for parasite replication. As such, understanding factors that affect parasite morphology is important in predicting the consequences of host-parasite interactions. Here, we studied how host diet affected the spore morphology of a protozoan parasite ( Ophryocystis elektroscirrha ), a specialist parasite of the monarch butterfly ( Danaus plexippus ). We found that different host plant species (milkweeds; Asclepias spp.) significantly affected parasite spore size. Previous studies have found that cardenolides, secondary chemicals in host plants of monarchs, can reduce parasite loads and increase the lifespan of infected butterflies. Adding to this benefit of high cardenolide milkweeds, we found that infected monarchs reared on milkweeds of higher cardenolide concentrations yielded smaller parasites, a potentially hidden characteristic of cardenolides that may have important implications for monarch-parasite interactions.

Context Dependency of a Marine Defensive Symbiosis over a Wide Geographic Distribution

NASA Astrophysics Data System (ADS)

Lopanik, N.; Linneman, J.; Mathew, M.

2016-02-01

The invasive, temperate marine bryozoan Bugula neritina possesses an uncultured, vertically-transmitted bacterial symbiont that produces natural products known as bryostatins. These unpalatable polyketides protect the host larvae from predation. In the western Atlantic, two host genotypes were thought to be restricted to differing latitudes based on the presence of the defensive symbiont: undefended aposymbiotic Type N animals were found at high latitudes, while defended symbiotic Type S colonies were found at low latitudes, where predation pressure is higher. We found that the host genotypes are more widespread than previously thought, but that the symbiont appeared to be restricted to hosts at lower latitudes, regardless of host phylotype, leading to the question of what factors are involved in restricting the symbiont's range. We performed reciprocal transplant experiments of symbiotic and antibiotic-cured hosts, and measured host growth, a proxy for fitness. Our data indicate that possession of the symbiont appears to present a physiological cost to the host. This cost may be more pronounced at higher latitudes where the benefit of symbiosis is less apparent. In addition, preliminary evidence suggests that symbiont titer in a Type S colony from North Carolina transplanted to Virginia is reduced over a period of nearly 4 months. Taken together, these results suggest that a combination of factors may play a role in the distribution of the defensive symbiont: (i) hosts that possess the symbiont are outcompeted by aposymbiotic conspecifics at high latitude and reduced levels of predation pressure; and (ii) symbiont growth may be inhibited or sanctioned by the host at high latitudes. As defensive symbiosis is an important trait in marine habitats, understanding factors that affect the distribution of both the host and symbiont are necessary to fully appreciate the ecological impact of symbiosis.

p53 Is a Host Cell Regulator during Herpes Simplex Encephalitis.

PubMed

Maruzuru, Yuhei; Koyanagi, Naoto; Takemura, Naoki; Uematsu, Satoshi; Matsubara, Daisuke; Suzuki, Yutaka; Arii, Jun; Kato, Akihisa; Kawaguchi, Yasushi

2016-08-01

p53 is a critical host cell factor in the cellular response to a broad range of stress factors. We recently reported that p53 is required for efficient herpes simplex virus 1 (HSV-1) replication in cell culture. However, a defined role for p53 in HSV-1 replication and pathogenesis in vivo remains elusive. In this study, we examined the effects of p53 on HSV-1 infection in vivo using p53-deficient mice. Following intracranial inoculation, p53 knockout reduced viral replication in the brains of mice and led to significantly reduced rates of mortality due to herpes simplex encephalitis. These results suggest that p53 is an important host cell regulator of HSV-1 replication and pathogenesis in the central nervous system (CNS). HSV-1 causes sporadic cases of encephalitis, which, even with antiviral therapy, can result in severe neurological defects and even death. Many host cell factors involved in the regulation of CNS HSV-1 infection have been investigated using genetically modified mice. However, most of these factors are immunological regulators and act via immunological pathways in order to restrict CNS HSV-1 infection. They therefore provide limited information on intrinsic host cell regulators that may be involved in the facilitation of CNS HSV-1 infection. Here we demonstrate that a host cell protein, p53, which has generally been considered a host cell restriction factor for various viral infections, is required for efficient HSV-1 replication and pathogenesis in the CNS of mice. This is the first report showing that p53 positively regulates viral replication and pathogenesis in vivo and provides insights into its molecular mechanism, which may suggest novel clinical treatment options for herpes simplex encephalitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Philometra floridensis (Nematoda: Philometridae) damages ovarian tissue without reducing host (Sciaenops ocellatus) fecundity.

PubMed

Bakenhaster, Micah D; Lowerre-Barbieri, Susan; Kiryu, Yasunari; Walters, Sarah; Fajer-Avila, Emma J

2014-04-03

The parasitic nematode Philometra floridensis infects the ovary of its only host, the economically important fish species Sciaenops ocellatus, but the factors influencing host susceptibility and potential pathogenic effects are unknown. Here we report new information on these topics from evaluations of infected and uninfected hosts collected from the northeastern Gulf of Mexico. Fish length and age were evaluated vis-à-vis nematode prevalence to check for ontogenetic differences in host susceptibility. To evaluate health and reproductive consequences of infection, we looked for effects in Fulton's condition factor (K) and batch fecundity estimates (BF), and we evaluated ovarian tissue histologically to check for oocyte atresia and other host responses. We observed localized pathological changes in fish ovarian tissue associated with female nematodes, including leucocytic exudates, granulomatous inflammation, and Langhans-type multinucleated giant cells; the hosts, however, appeared to maintain high fecundity and actually exhibited, on average, better health index scores and higher relative fecundity than did uninfected fish. These differences are likely explained by the parasite's tendency to disproportionately infect the largest, actively spawning fish and by the localization of pathogenic changes, which could have masked effects that otherwise would have been reflected in mass-based health indicators. Although we did not detect negative effects on measures of overall health or reproductive output, further research is needed to better elucidate the relationship between these parasites and other factors affecting host reproductive potential, such as egg quality.

Host-Plant Specialization Mediates the Influence of Plant Abundance on Host Use by Flower Head-Feeding Insects.

PubMed

Nobre, Paola A F; Bergamini, Leonardo L; Lewinsohn, Thomas M; Jorge, Leonardo R; Almeida-Neto, Mário

2016-02-01

Among-population variation in host use is a common phenomenon in herbivorous insects. The simplest and most trivial explanation for such variation in host use is the among-site variation in plant species composition. Another aspect that can influence spatial variation in host use is the relative abundance of each host-plant species compared to all available hosts. Here, we used endophagous insects that develop in flower heads of Asteraceae species as a study system to investigate how plant abundance influences the pattern of host-plant use by herbivorous insects with distinct levels of host-range specialization. Only herbivores recorded on three or more host species were included in this study. In particular, we tested two related hypotheses: 1) plant abundance has a positive effect on the host-plant preference of herbivorous insects, and 2) the relative importance of plant abundance to host-plant preference is greater for herbivorous species that use a wider range of host-plant species. We analyzed 11 herbivore species in 20 remnants of Cerrado in Southeastern Brazil. For 8 out of 11 herbivore species, plant abundance had a positive influence on host use. In contrast to our expectation, both the most specialized and the most generalist herbivores showed a stronger positive effect of plant species abundance in host use. Thus, we found evidence that although the abundance of plant species is a major factor determining the preferential use of host plants, its relative importance is mediated by the host-range specialization of herbivores.

Review of osteoimmunology and the host response in endodontic and periodontal lesions

PubMed Central

Graves, Dana T.; Oates, Thomas; Garlet, Gustavo P.

2011-01-01

Both lesions of endodontic origin and periodontal diseases involve the host response to bacteria and the formation of osteolytic lesions. Important for both is the upregulation of inflammatory cytokines that initiate and sustain the inflammatory response. Also important are chemokines that induce recruitment of leukocyte subsets and bone-resorptive factors that are largely produced by recruited inflammatory cells. However, there are differences also. Lesions of endodontic origin pose a particular challenge since that bacteria persist in a protected reservoir that is not readily accessible to the immune defenses. Thus, experiments in which the host response is inhibited in endodontic lesions tend to aggravate the formation of osteolytic lesions. In contrast, bacteria that invade the periodontium appear to be less problematic so that blocking arms of the host response tend to reduce the disease process. Interestingly, both lesions of endodontic origin and periodontitis exhibit inflammation that appears to inhibit bone formation. In periodontitis, the spatial location of the inflammation is likely to be important so that a host response that is restricted to a subepithelial space is associated with gingivitis, while a host response closer to bone is linked to bone resorption and periodontitis. However, the persistence of inflammation is also thought to be important in periodontitis since inflammation present during coupled bone formation may limit the capacity to repair the resorbed bone. PMID:21547019

Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication

PubMed Central

Lahaye, Xavier; Satoh, Takeshi; Gentili, Matteo; Cerboni, Silvia; Silvin, Aymeric; Conrad, Cécile; Ahmed-Belkacem, Abdelhakim; Rodriguez, Elisa C.; Guichou, Jean-François; Bosquet, Nathalie; Piel, Matthieu; Le Grand, Roger; King, Megan C.; Pawlotsky, Jean-Michel; Manel, Nicolas

2016-01-01

Summary During the early phase of replication, HIV reverse transcribes its RNA and crosses the nuclear envelope while escaping host antiviral defenses. The host factor Cyclophilin A (CypA) is essential for these steps and binds the HIV capsid; however, the mechanism underlying this effect remains elusive. Here, we identify related capsid mutants in HIV-1, HIV-2, and SIVmac that are restricted by CypA. This antiviral restriction of mutated viruses is conserved across species and prevents nuclear import of the viral cDNA. Importantly, the inner nuclear envelope protein SUN2 is required for the antiviral activity of CypA. We show that wild-type HIV exploits SUN2 in primary CD4+ T cells as an essential host factor that is required for the positive effects of CypA on reverse transcription and infection. Altogether, these results establish essential CypA-dependent functions of SUN2 in HIV infection at the nuclear envelope. PMID:27149839

Immune response and immunopathology during toxoplasmosis1

PubMed Central

Dupont, Christopher D.; Christian, David A.; Hunter, Christopher A.

2012-01-01

Toxoplasma gondii is a protozoan parasite of medical and veterinary significance that is able to infect any warm-blooded vertebrate host. In addition to its importance to public health, several inherent features of the biology of T. gondii have made it an important model organism to study host-pathogen interactions. One factor is the genetic tractability of the parasite, which allows studies on the microbial factors that affect virulence and allows the development of tools that facilitate immune studies. Additionally, mice are natural hosts for T. gondii, and the availability of numerous reagents to study the murine immune system makes this an ideal experimental system to understand the functions of cytokines and effector mechanisms involved in immunity to intracellular microorganisms. In this article, we will review current knowledge of the innate and adaptive immune responses required for resistance to toxoplasmosis, the events that lead to the development of immunopathology, and the natural regulatory mechanisms that limit excessive inflammation during this infection. PMID:22955326

Candida spp. in periodontal disease: a brief review.

PubMed

Sardi, Janaina C O; Duque, Cristiane; Mariano, Flávia S; Peixoto, Iza T A; Höfling, José F; Gonçalves, Reginaldo B

2010-06-01

Although the main reservoir of Candida spp. is believed to be the buccal mucosa, these microorganisms can coaggregate with bacteria in subgingival biofilm and adhere to epithelial cells. Such interactions are associated with the capacity of Candida spp. to invade gingival conjunctive tissue, and may be important in the microbial colonization that contributes to progression of oral alterations caused by diabetes mellitus, some medications, and immunosuppressive diseases such as AIDS. In addition, immune deficiency can result in proliferation of Candida spp. and germination of forms that are more virulent and have a higher capacity to adhere to and penetrate cells in host tissues. The virulence factors of Candida spp. increase host susceptibility to proliferation of these microorganisms and are likely to be important in the study of periodontal disease. Herein, we briefly review the literature pertaining to the role of Candida spp. in periodontal disease, and consider the main virulence factors, the host immune response to these microorganisms, and the effect of concomitant immunosuppressive conditions.

Dermatophytes activate skin keratinocytes via mitogen-activated protein kinase signaling and induce immune responses.

PubMed

Achterman, Rebecca R; Moyes, David L; Thavaraj, Selvam; Smith, Adam R; Blair, Kris M; White, Theodore C; Naglik, Julian R

2015-04-01

Dermatophytes cause superficial and cutaneous fungal infections in immunocompetent hosts and invasive disease in immunocompromised hosts. However, the host mechanisms that regulate innate immune responses against these fungi are largely unknown. Here, we utilized commercially available epidermal tissues and primary keratinocytes to assess (i) damage induction by anthropophilic, geophilic, and zoophilic dermatophyte strains and (ii) the keratinocyte signaling pathways, transcription factors, and proinflammatory responses induced by a representative dermatophyte, Trichophyton equinum. Initially, five dermatophyte species were tested for their ability to invade, cause tissue damage, and induce cytokines, with Microsporum gypseum inducing the greatest level of damage and cytokine release. Using T. equinum as a representative dermatophyte, we found that the mitogen-activated protein kinase (MAPK) pathways were predominantly affected, with increased levels of phospho-p38 and phospho-Jun N-terminal protein kinase (JNK) but decreased levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2). Notably, the NF-κB and PI3K pathways were largely unaffected. T. equinum also significantly increased expression of the AP-1-associated transcription factor, c-Fos, and the MAPK regulatory phosphatase, MKP1. Importantly, the ability of T. equinum to invade, cause tissue damage, activate signaling and transcription factors, and induce proinflammatory responses correlated with germination, indicating that germination may be important for dermatophyte virulence and host immune activation. Copyright © 2015, Achterman et al.

Preference‒performance linkage in the diamondback moth, Plutella xylostella , and implications for its management

PubMed Central

Marchioro, Marchioro; Foerster, Luís Amilton

2014-01-01

Abstract Host plants affect development, survival, and reproduction of phytophagous insects. In the case of holometabolous species, whose larvae have little mobility to find a host plant, the ability of females to discriminate hosts on the basis of their nutritional quality may be an important factor determining insect performance. The preference‒performance correlation hypothesis states that females will choose to lay their eggs on host plants that provide the best offspring performance. The effects of three cultivated and two wild brassicas (Brassicales: Brassicaceae) on the biology of the diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), an important pest of brassicas, were investigated. Based on these data, the preference–performance correlation hypothesis was tested. The results allowed the discussion of the possible role of wild brassicas on population dynamics of the pest. The life table parameters net reproduction rate and intrinsic rate of increase were used as indicatives of insect performance because they provide a detailed description of the survivorship, development, and reproduction of a population. Development, survival, and reproduction were affected by the cultivated and wild brassicas. Both net reproduction rate and intrinsic rate of increase were lower in individuals fed on wild brassicas, which indicates that brassicas are not nutritionally suitable for P. xylostella . Nevertheless, females showed no oviposition preference among host plants. The results showed that host plant quality might not be the only factor determining host selection by female P. xylostella . Results also suggest that wild brassicas may serve as a refuge for P. xylostella , favoring pest survival when crops are disturbed by insecticide application, irrigation, or ploughing. PMID:25368041

Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C

PubMed Central

Wilson, Eleanor M.; Rosenthal, Elana S.; Kattakuzhy, Sarah; Tang, Lydia

2016-01-01

SUMMARY Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors. PMID:27795306

The influence of climatic niche preferences on the population genetic structure of a mistletoe species complex.

PubMed

Ramírez-Barahona, Santiago; González, Clementina; González-Rodríguez, Antonio; Ornelas, Juan Francisco

2017-06-01

The prevalent view on genetic structuring in parasitic plants is that host-race formation is caused by varying degrees of host specificity. However, the relative importance of ecological niche divergence and host specificity to population differentiation remains poorly understood. We evaluated the factors associated with population differentiation in mistletoes of the Psittacanthus schiedeanus complex (Loranthaceae) in Mexico. We used genetic data from chloroplast sequences and nuclear microsatellites to study population genetic structure and tested its association with host preferences and climatic niche variables. Pairwise genetic differentiation was associated with environmental and host preferences, independent of geography. However, environmental predictors appeared to be more important than host preferences to explain genetic structure, supporting the hypothesis that the occurrence of the parasite is largely determined by its own climatic niche and, to a lesser degree, by host specificity. Genetic structure is significant within this mistletoe species complex, but the processes associated with this structure appear to be more complex than previously thought. Although host specificity was not supported as the major determinant of population differentiation, we consider this to be part of a more comprehensive ecological model of mistletoe host-race formation that incorporates the effects of climatic niche evolution. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

PubMed

Morrot, Alexandre; Villar, Silvina R; González, Florencia B; Pérez, Ana R

2016-01-01

Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease.

Biotic mortality factors affecting emerald ash borer (Agrilus planipennis) are highly dependent on life stage and host tree crown condition

USDA-ARS?s Scientific Manuscript database

Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990’s. Although host plant resistance and natural enemies are known to be important sources ...

Biological factors contributing to bark and ambrosia beetle species diversification.

PubMed

Gohli, Jostein; Kirkendall, Lawrence R; Smith, Sarah M; Cognato, Anthony I; Hulcr, Jiri; Jordal, Bjarte H

2017-05-01

The study of species diversification can identify the processes that shape patterns of species richness across the tree of life. Here, we perform comparative analyses of species diversification using a large dataset of bark beetles. Three examined covariates-permanent inbreeding (sibling mating), fungus farming, and major host type-represent a range of factors that may be important for speciation. We studied the association of these covariates with species diversification while controlling for evolutionary lag on adaptation. All three covariates were significantly associated with diversification, but fungus farming showed conflicting patterns between different analyses. Genera that exhibited interspecific variation in host type had higher rates of species diversification, which may suggest that host switching is a driver of species diversification or that certain host types or forest compositions facilitate colonization and thus allopatric speciation. Because permanent inbreeding is thought to facilitate dispersal, the positive association between permanent inbreeding and diversification rates suggests that dispersal ability may contribute to species richness. Bark beetles are ecologically unique; however, our results indicate that their impressive species diversity is largely driven by mechanisms shown to be important for many organism groups. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

HIV and host immunogenetics: unraveling the role of HLA-C.

PubMed

Bardeskar, N S; Mania-Pramanik, J

2016-11-01

Host genetic factors play a major role in determining the outcome of many infections including human immunodeficiency virus (HIV). Multiple host factors have been studied till date showing their varied role in susceptibility or resistance to HIV infection. HLA-C, however, has been recently started gaining interest in researchers mind revealing its polymorphisms to have an important effect on viral load set-points, disease progression as well as transmission. In this review report, we have compiled these significant findings of HLA-C in HIV infection, in an attempt to highlight the need for further research in the area in different ethnic population to establish its role in the infection. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human gut microbiota: does diet matter?

PubMed

Maukonen, Johanna; Saarela, Maria

2015-02-01

The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated.

Influence of host diet and phylogeny on parasite sharing by fish in a diverse tropical floodplain.

PubMed

Lima, L B; Bellay, S; Giacomini, H C; Isaac, A; Lima-Junior, D P

2016-03-01

The patterns of parasite sharing among hosts have important implications for ecosystem structure and functioning, and are influenced by several ecological and evolutionary factors associated with both hosts and parasites. Here we evaluated the influence of fish diet and phylogenetic relatedness on the pattern of infection by parasites with contrasting life history strategies in a freshwater ecosystem of key ecological importance in South America. The studied network of interactions included 52 fish species, which consumed 58 food types and were infected with 303 parasite taxa. Our results show that both diet and evolutionary history of hosts significantly explained parasite sharing; phylogenetically close fish species and/or species sharing food types tend to share more parasites. However, the effect of diet was observed only for endoparasites in contrast to ectoparasites. These results are consistent with the different life history strategies and selective pressures imposed on these groups: endoparasites are in general acquired via ingestion by their intermediate hosts, whereas ectoparasites actively seek and attach to the gills, body surface or nostrils of its sole host, thus not depending directly on its feeding habits.

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

PubMed Central

Audsley, Michelle D; Moseley, Gregory W

2013-01-01

The paramyxoviruses are a family of > 30 viruses that variously infect humans, other mammals and fish to cause diverse outcomes, ranging from asymptomatic to lethal disease, with the zoonotic paramyxoviruses Nipah and Hendra showing up to 70% case-fatality rate in humans. The capacity to evade host immunity is central to viral infection, and paramyxoviruses have evolved multiple strategies to overcome the host interferon (IFN)-mediated innate immune response through the activity of their IFN-antagonist proteins. Although paramyxovirus IFN antagonists generally target common factors of the IFN system, including melanoma differentiation associated factor 5, retinoic acid-inducible gene-I, signal transducers and activators of transcription (STAT)1 and STAT2, and IFN regulatory factor 3, the mechanisms of antagonism show remarkable diversity between different genera and even individual members of the same genus; the reasons for this diversity, however, are not currently understood. Here, we review the IFN antagonism strategies of paramyxoviruses, highlighting mechanistic differences observed between individual species and genera. We also discuss potential sources of this diversity, including biological differences in the host and/or tissue specificity of different paramyxoviruses, and potential effects of experimental approaches that have largely relied on in vitro systems. Importantly, recent studies using recombinant virus systems and animal infection models are beginning to clarify the importance of certain mechanisms of IFN antagonism to in vivo infections, providing important indications not only of their critical importance to virulence, but also of their potential targeting for new therapeutic/vaccine approaches. PMID:24175230

Genetic Structure in the Seabuckthorn Carpenter Moth (Holcocerus hippophaecolus) in China: The Role of Outbreak Events, Geographical and Host Factors

PubMed Central

Tao, Jing; Chen, Min; Zong, Shi-Xiang; Luo, You-Qing

2012-01-01

Understanding factors responsible for structuring genetic diversity is of fundamental importance in evolutionary biology. The seabuckthorn carpenter moth (Holcocerus hippophaecolus Hua) is a native species throughout the north of China and is considered the main threat to seabuckthorn, Hippophae rhamnoides L. We assessed the influence of outbreaks, environmental factors and host species in shaping the genetic variation and structure of H. hippophaecolus by using Amplified Fragment Length Polymorphism (AFLP) markers. We rejected the hypothesis that outbreak-associated genetic divergence exist, as evidenced by genetic clusters containing a combination of populations from historical outbreak areas, as well as non-outbreak areas. Although a small number of markers (4 of 933 loci) were identified as candidates under selection in response to population densities. H. hippophaecolus also did not follow an isolation-by-distance pattern. We rejected the hypothesis that outbreak and drought events were driving the genetic structure of H. hippophaecolus. Rather, the genetic structure appears to be influenced by various confounding bio-geographical factors. There were detectable genetic differences between H. hippophaecolus occupying different host trees from within the same geographic location. Host-associated genetic divergence should be confirmed by further investigation. PMID:22291983

Gut Microbiota: A Contributing Factor to Obesity

PubMed Central

Harakeh, Steve M.; Khan, Imran; Kumosani, Taha; Barbour, Elie; Almasaudi, Saad B.; Bahijri, Suhad M.; Alfadul, Sulaiman M.; Ajabnoor, Ghada M. A.; Azhar, Esam I.

2016-01-01

Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014 microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity. PMID:27625997

Identifying patients at high risk of tuberculosis recurrence.

PubMed

Sadikot, Ruxana T

2016-12-01

Several studies have been done in relation to recurrence of tuberculosis (TB) following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs. In addition to treatment failure related to medication adherence, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include: malnutrition; human immunodeficiency virus; substance abuse including tobacco use; comorbidity such as diabetes, renal failure and systemic diseases, especially immunosuppressive states; and environmental exposure such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being discovered. Information on temporal and geographical trends of TB cases as well as genotyping might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and defining host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence. Copyright © 2016.

Patients at high risk of tuberculosis recurrence.

PubMed

Mirsaeidi, Mehdi; Sadikot, Ruxana T

2018-01-01

Recurrent tuberculosis (TB) continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

Novel Disease Susceptibility Factors for Fungal Necrotrophic Pathogens in Arabidopsis

PubMed Central

García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

2015-01-01

Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens. PMID:25830627

Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen.

PubMed

Awad, Milena M; Johanesen, Priscilla A; Carter, Glen P; Rose, Edward; Lyras, Dena

2014-01-01

The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions.

Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen

PubMed Central

Awad, Milena M; Johanesen, Priscilla A; Carter, Glen P; Rose, Edward; Lyras, Dena

2014-01-01

The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions. PMID:25483328

Perspectives on the Trypanosoma cruzi–host cell receptor interactions

PubMed Central

Villalta, Fernando; Scharfstein, Julio; Ashton, Anthony W.; Tyler, Kevin M.; Guan, Fangxia; Mukherjee, Shankar; Lima, Maria F.; Alvarez, Sandra; Weiss, Louis M.; Huang, Huan; Machado, Fabiana S.

2009-01-01

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets. PMID:19283409

Factor H: A Complement Regulator in Health and Disease, and a Mediator of Cellular Interactions

PubMed Central

Kopp, Anne; Hebecker, Mario; Svobodová, Eliška; Józsi, Mihály

2012-01-01

Complement is an essential part of innate immunity as it participates in host defense against infections, disposal of cellular debris and apoptotic cells, inflammatory processes and modulation of adaptive immune responses. Several soluble and membrane-bound regulators protect the host from the potentially deleterious effects of uncontrolled and misdirected complement activation. Factor H is a major soluble regulator of the alternative complement pathway, but it can also bind to host cells and tissues, protecting them from complement attack. Interactions of factor H with various endogenous ligands, such as pentraxins, extracellular matrix proteins and DNA are important in limiting local complement-mediated inflammation. Impaired regulatory as well as ligand and cell recognition functions of factor H, caused by mutations or autoantibodies, are associated with the kidney diseases: atypical hemolytic uremic syndrome and dense deposit disease and the eye disorder: age-related macular degeneration. In addition, factor H binds to receptors on host cells and is involved in adhesion, phagocytosis and modulation of cell activation. In this review we discuss current concepts on the physiological and pathophysiological roles of factor H in light of new data and recent developments in our understanding of the versatile roles of factor H as an inhibitor of complement activation and inflammation, as well as a mediator of cellular interactions. A detailed knowledge of the functions of factor H in health and disease is expected to unravel novel therapeutic intervention possibilities and to facilitate the development or improvement of therapies. PMID:24970127

Spatial structure and nest demography reveal the influence of competition, parasitism and habitat quality on slavemaking ants and their hosts

PubMed Central

2011-01-01

Background Natural communities are structured by intra-guild competition, predation or parasitism and the abiotic environment. We studied the relative importance of these factors in two host-social parasite ecosystems in three ant communities in Europe (Bavaria) and North America (New York, West Virginia). We tested how these factors affect colony demography, life-history and the spatial pattern of colonies, using a large sample size of more than 1000 colonies. The strength of competition was measured by the distance to the nearest competitor. Distance to the closest social parasite colony was used as a measure of parasitism risk. Nest sites (i.e., sticks or acorns) are limited in these forest ecosystems and we therefore included nest site quality as an abiotic factor in the analysis. In contrast to previous studies based on local densities, we focus here on the positioning and spatial patterns and we use models to compare our predictions to random expectations. Results Colony demography was universally affected by the size of the nest site with larger and more productive colonies residing in larger nest sites of higher quality. Distance to the nearest competitor negatively influenced host demography and brood production in the Bavarian community, pointing to an important role of competition, while social parasitism was less influential in this community. The New York community was characterized by the highest habitat variability, and productive colonies were clustered in sites of higher quality. Colonies were clumped on finer spatial scales, when we considered only the nearest neighbors, but more regularly distributed on coarser scales. The analysis of spatial positioning within plots often produced different results compared to those based on colony densities. For example, while host and slavemaker densities are often positively correlated, slavemakers do not nest closer to potential host colonies than expected by random. Conclusions The three communities are differently affected by biotic and abiotic factors. Some of the differences can be attributed to habitat differences and some to differences between the two slavemaking-host ecosystems. The strong effect of competition in the Bavarian community points to the scarcity of resources in this uniform habitat compared to the other more diverse sites. The decrease in colony aggregation with scale indicates fine-scale resource hotspots: colonies are locally aggregated in small groups. Our study demonstrates that species relationships vary across scales and spatial patterns can provide important insights into species interactions. These results could not have been obtained with analyses based on local densities alone. Previous studies focused on social parasitism and its effect on host colonies. The broader approach taken here, considering several possible factors affecting colony demography and not testing each one in isolation, shows that competition and environmental variability can have a similar strong impact on demography and life-history of hosts. We conclude that the effects of parasites or predators should be studied in parallel to other ecological influences. PMID:21443778

Spatial structure and nest demography reveal the influence of competition, parasitism and habitat quality on slavemaking ants and their hosts.

PubMed

Scharf, Inon; Fischer-Blass, Birgit; Foitzik, Susanne

2011-03-28

Natural communities are structured by intra-guild competition, predation or parasitism and the abiotic environment. We studied the relative importance of these factors in two host-social parasite ecosystems in three ant communities in Europe (Bavaria) and North America (New York, West Virginia). We tested how these factors affect colony demography, life-history and the spatial pattern of colonies, using a large sample size of more than 1000 colonies. The strength of competition was measured by the distance to the nearest competitor. Distance to the closest social parasite colony was used as a measure of parasitism risk. Nest sites (i.e., sticks or acorns) are limited in these forest ecosystems and we therefore included nest site quality as an abiotic factor in the analysis. In contrast to previous studies based on local densities, we focus here on the positioning and spatial patterns and we use models to compare our predictions to random expectations. Colony demography was universally affected by the size of the nest site with larger and more productive colonies residing in larger nest sites of higher quality. Distance to the nearest competitor negatively influenced host demography and brood production in the Bavarian community, pointing to an important role of competition, while social parasitism was less influential in this community. The New York community was characterized by the highest habitat variability, and productive colonies were clustered in sites of higher quality. Colonies were clumped on finer spatial scales, when we considered only the nearest neighbors, but more regularly distributed on coarser scales. The analysis of spatial positioning within plots often produced different results compared to those based on colony densities. For example, while host and slavemaker densities are often positively correlated, slavemakers do not nest closer to potential host colonies than expected by random. The three communities are differently affected by biotic and abiotic factors. Some of the differences can be attributed to habitat differences and some to differences between the two slavemaking-host ecosystems. The strong effect of competition in the Bavarian community points to the scarcity of resources in this uniform habitat compared to the other more diverse sites. The decrease in colony aggregation with scale indicates fine-scale resource hotspots: colonies are locally aggregated in small groups. Our study demonstrates that species relationships vary across scales and spatial patterns can provide important insights into species interactions. These results could not have been obtained with analyses based on local densities alone. Previous studies focused on social parasitism and its effect on host colonies. The broader approach taken here, considering several possible factors affecting colony demography and not testing each one in isolation, shows that competition and environmental variability can have a similar strong impact on demography and life-history of hosts. We conclude that the effects of parasites or predators should be studied in parallel to other ecological influences.

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

PubMed Central

Campos, Rafael K.; Wong, Benjamin; Lu, Yi-Fan; Shi, Pei-Yong; Pompon, Julien

2016-01-01

ABSTRACT The Flavivirus genus contains several arthropod-borne viruses that pose global health threats, including dengue viruses (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). In order to understand how these viruses replicate in human cells, we previously conducted genome-scale RNA interference screens to identify candidate host factors. In these screens, we identified ribosomal proteins RPLP1 and RPLP2 (RPLP1/2) to be among the most crucial putative host factors required for DENV and YFV infection. RPLP1/2 are phosphoproteins that bind the ribosome through interaction with another ribosomal protein, RPLP0, to form a structure termed the ribosomal stalk. RPLP1/2 were validated as essential host factors for DENV, YFV, and ZIKV infection in two human cell lines: A549 lung adenocarcinoma and HuH-7 hepatoma cells, and for productive DENV infection of Aedes aegypti mosquitoes. Depletion of RPLP1/2 caused moderate cell-line-specific effects on global protein synthesis, as determined by metabolic labeling. In A549 cells, global translation was increased, while in HuH-7 cells it was reduced, albeit both of these effects were modest. In contrast, RPLP1/2 knockdown strongly reduced early DENV protein accumulation, suggesting a requirement for RPLP1/2 in viral translation. Furthermore, knockdown of RPLP1/2 reduced levels of DENV structural proteins expressed from an exogenous transgene. We postulate that these ribosomal proteins are required for efficient translation elongation through the viral open reading frame. In summary, this work identifies RPLP1/2 as critical flaviviral host factors required for translation. IMPORTANCE Flaviviruses cause important diseases in humans. Examples of mosquito-transmitted flaviviruses include dengue, yellow fever and Zika viruses. Viruses require a plethora of cellular factors to infect cells, and the ribosome plays an essential role in all viral infections. The ribosome is a complex macromolecular machine composed of RNA and proteins and it is responsible for protein synthesis. We identified two specific ribosomal proteins that are strictly required for flavivirus infection of human cells and mosquitoes: RPLP1 and RPLP2 (RPLP1/2). These proteins are part of a structure known as the ribosomal stalk and help orchestrate the elongation phase of translation. We show that flaviviruses are particularly dependent on the function of RPLP1/2. Our findings suggest that ribosome composition is an important factor for virus translation and may represent a regulatory layer for translation of specific cellular mRNAs. PMID:27974556

Hiding in plain sight: immune evasion by the staphylococcal protein SdrE.

PubMed

Herr, Andrew B; Thorman, Alexander W

2017-05-10

The human immune system is responsible for identification and destruction of invader cells, such as the bacterial pathogen Staphylococcus aureus In response, S. aureus brings to the fight a large number of virulence factors, including several that allow it to evade the host immune response. The staphylococcal surface protein SdrE was recently reported to bind to complement Factor H, an important regulator of complement activation. Factor H attaches to the surface of host cells to inhibit complement activation and amplification, preventing the destruction of the host cell. SdrE binding to Factor H allows S. aureus to mimic a host cell and reduces bacterial killing by granulocytes. In a new study published in Biochemical Journal , Zhang et al. describe crystal structures of SdrE and its complex with the C-terminal portion of Factor H. The structure of SdrE and its interaction with the Factor H peptide closely resemble a family of surface proteins that recognize extracellular matrix components such as fibrinogen. However, unbound SdrE forms a novel 'Closed' conformation with an occluded peptide-binding groove. These structures reveal a fascinating mechanism for immune evasion and provide a potential avenue for the development of novel antimicrobial agents to target SdrE. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition.

PubMed

Li, Qisheng; Sodroski, Catherine; Lowey, Brianna; Schweitzer, Cameron J; Cha, Helen; Zhang, Fang; Liang, T Jake

2016-07-05

Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.

Comparative Transcriptomics Highlights the Role of the Activator Protein 1 Transcription Factor in the Host Response to Ebolavirus

PubMed Central

Todd, Shawn; Boyd, Victoria; Tachedjian, Mary; Klein, Reuben; Shiell, Brian; Dearnley, Megan; McAuley, Alexander J.; Woon, Amanda P.; Purcell, Anthony W.; Marsh, Glenn A.; Baker, Michelle L.

2017-01-01

ABSTRACT Ebolavirus and Marburgvirus comprise two genera of negative-sense single-stranded RNA viruses that cause severe hemorrhagic fevers in humans. Despite considerable research efforts, the molecular events following Ebola virus (EBOV) infection are poorly understood. With the view of identifying host factors that underpin EBOV pathogenesis, we compared the transcriptomes of EBOV-infected human, pig, and bat kidney cells using a transcriptome sequencing (RNA-seq) approach. Despite a significant difference in viral transcription/replication between the cell lines, all cells responded to EBOV infection through a robust induction of extracellular growth factors. Furthermore, a significant upregulation of activator protein 1 (AP1) transcription factor complex members FOS and JUN was observed in permissive cell lines. Functional studies focusing on human cells showed that EBOV infection induces protein expression, phosphorylation, and nuclear accumulation of JUN and, to a lesser degree, FOS. Using a luciferase-based reporter, we show that EBOV infection induces AP1 transactivation activity within human cells at 48 and 72 h postinfection. Finally, we show that JUN knockdown decreases the expression of EBOV-induced host gene expression. Taken together, our study highlights the role of AP1 in promoting the host gene expression profile that defines EBOV pathogenesis. IMPORTANCE Many questions remain about the molecular events that underpin filovirus pathophysiology. The rational design of new intervention strategies, such as postexposure therapeutics, will be significantly enhanced through an in-depth understanding of these molecular events. We believe that new insights into the molecular pathogenesis of EBOV may be possible by examining the transcriptomic response of taxonomically diverse cell lines (derived from human, pig, and bat). We first identified the responsive pathways using an RNA-seq-based transcriptomics approach. Further functional and computational analysis focusing on human cells highlighted an important role for the AP1 transcription factor in mediating the transcriptional response to EBOV infection. Our study sheds new light on how host transcription factors respond to and promote the transcriptional landscape that follows viral infection. PMID:28931675

Spatial and Temporal Dynamics of Pacific Oyster Hemolymph Microbiota across Multiple Scales

PubMed Central

Lokmer, Ana; Goedknegt, M. Anouk; Thieltges, David W.; Fiorentino, Dario; Kuenzel, Sven; Baines, John F.; Wegner, K. Mathias

2016-01-01

Unveiling the factors and processes that shape the dynamics of host associated microbial communities (microbiota) under natural conditions is an important part of understanding and predicting an organism's response to a changing environment. The microbiota is shaped by host (i.e., genetic) factors as well as by the biotic and abiotic environment. Studying natural variation of microbial community composition in multiple host genetic backgrounds across spatial as well as temporal scales represents a means to untangle this complex interplay. Here, we combined a spatially-stratified with a longitudinal sampling scheme within differentiated host genetic backgrounds by reciprocally transplanting Pacific oysters between two sites in the Wadden Sea (Sylt and Texel). To further differentiate contingent site from host genetic effects, we repeatedly sampled the same individuals over a summer season to examine structure, diversity and dynamics of individual hemolymph microbiota following experimental removal of resident microbiota by antibiotic treatment. While a large proportion of microbiome variation could be attributed to immediate environmental conditions, we observed persistent effects of antibiotic treatment and translocation suggesting that hemolymph microbial community dynamics is subject to within-microbiome interactions and host population specific factors. In addition, the analysis of spatial variation revealed that the within-site microenvironmental heterogeneity resulted in high small-scale variability, as opposed to large-scale (between-site) stability. Similarly, considerable within-individual temporal variability was in contrast with the overall temporal stability at the site level. Overall, our longitudinal, spatially-stratified sampling design revealed that variation in hemolymph microbiota is strongly influenced by site and immediate environmental conditions, whereas internal microbiome dynamics and oyster-related factors add to their long-term stability. The combination of small and large scale resolution of spatial and temporal observations therefore represents a crucial but underused tool to study host-associated microbiome dynamics. PMID:27630625

Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy.

PubMed

Kuo, Shu-Ming; Chen, Chi-Jene; Chang, Shih-Cheng; Liu, Tzu-Jou; Chen, Yi-Hsiang; Huang, Sheng-Yu; Shih, Shin-Ru

2017-06-13

Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2 627 E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2 627 K (human signature) and PB2 627 E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2 627 E than PB2 627 K in transfected human cells. Stronger binding of TUFM to avian-signature PB2 590 G/ 591 Q and PB2 627 E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2 627 E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2 627 E viruses, but not PB2 627 K viruses. In addition, enhanced levels of interaction between TUFM and PB2 627 E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2 627 E virus; however, autophagy remained consistent in PB2 627 K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy. IMPORTANCE An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both critical to the prevention and control of emerging viruses that cross species barriers to target new hosts. Using a proteomic approach, we revealed a novel role for TUFM as a host restriction factor that exerts an inhibitory effect on avian-signature PB2 627 E influenza virus propagation in human cells. We further found that increased TUFM-dependent autophagy correlates with the inhibitory effect on avian-signature influenza virus replication and may serve as a key intrinsic mechanism to restrict avian influenza virus infection in humans. These findings provide new insight regarding the TUFM mitochondrial protein and may have important implications for the development of novel antiviral strategies. Copyright © 2017 Kuo et al.

Host-parasite coevolution: genetic variation in a virus population and the interaction with a host gene.

PubMed

Wilfert, L; Jiggins, F M

2010-07-01

Host-parasite coevolution is considered to be an important factor in maintaining genetic variation in resistance to pathogens. Drosophila melanogaster is naturally infected by the sigma virus, a vertically transmitted and host-specific pathogen. In fly populations, there is a large amount of genetic variation in the transmission rate from parent to offspring, much of which is caused by major-effect resistance polymorphisms. We have found that there are similarly high levels of genetic variation in the rate of paternal transmission among 95 different isolates of the virus as in the host. However, when we examined a transmission-blocking gene in the host, we found that it was effective across virus isolates. Therefore, the high levels of genetic variation observed in this system do not appear to be maintained because of coevolution resulting from interactions between this host gene and parasite genes.

Host nutrition alters the variance in parasite transmission potential

PubMed Central

Vale, Pedro F.; Choisy, Marc; Little, Tom J.

2013-01-01

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts. PMID:23407498

Host nutrition alters the variance in parasite transmission potential.

PubMed

Vale, Pedro F; Choisy, Marc; Little, Tom J

2013-04-23

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts.

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells.

PubMed

Nain, Minu; Mukherjee, Sriparna; Karmakar, Sonali Porey; Paton, Adrienne W; Paton, James C; Abdin, M Z; Basu, Anirban; Kalia, Manjula; Vrati, Sudhanshu

2017-03-15

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral encephalitis in Southeast Asia with potential to become a global pathogen. Here, we identify glucose-regulated protein 78 (GRP78) as an important host protein for virus entry and replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV envelope protein domain III. GRP78 was found to be expressed on the plasma membranes of Neuro2a cells, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against GRP78 significantly inhibited JEV entry in all three cell types, suggesting an important role of the protein in virus entry. Depletion of GRP78 by small interfering RNA (siRNA) significantly blocked JEV entry into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies showed extensive colocalization of GRP78 with JEV envelope protein in virus-infected cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, GRP78 was shown to have an important role in JEV replication, as treatment of cells post-virus entry with subtilase cytotoxin that specifically cleaved GRP78 led to a substantial reduction in viral RNA replication and protein synthesis, resulting in significantly reduced extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life cycle and could be a potential therapeutic target. IMPORTANCE Recent years have seen a rapid spread of mosquito-borne diseases caused by flaviviruses. The flavivirus family includes West Nile, dengue, Japanese encephalitis, and Zika viruses, which are major threats to public health with potential to become global pathogens. JEV is the major cause of viral encephalitis in several parts of Southeast Asia, affecting a predominantly pediatric population with a high mortality rate. This study is focused on identification of crucial host factors that could be targeted to cripple virus infection and ultimately lead to development of effective antivirals. We have identified a cellular protein, GRP78, that plays a dual role in virus entry and virus replication, two crucial steps of the virus life cycle, and thus is a novel host factor that could be a potential therapeutic target. Copyright © 2017 American Society for Microbiology.

Quantitative Proteomic Analysis of the Influenza A Virus Nonstructural Proteins NS1 and NS2 during Natural Cell Infection Identifies PACT as an NS1 Target Protein and Antiviral Host Factor

PubMed Central

Tawaratsumida, Kazuki; Phan, Van; Hrincius, Eike R.; High, Anthony A.; Webby, Richard; Redecke, Vanessa

2014-01-01

ABSTRACT Influenza A virus (IAV) replication depends on the interaction of virus proteins with host factors. The viral nonstructural protein 1 (NS1) is essential in this process by targeting diverse cellular functions, including mRNA splicing and translation, cell survival, and immune defense, in particular the type I interferon (IFN-I) response. In order to identify host proteins targeted by NS1, we established a replication-competent recombinant IAV that expresses epitope-tagged forms of NS1 and NS2, which are encoded by the same gene segment, allowing purification of NS proteins during natural cell infection and analysis of interacting proteins by quantitative mass spectrometry. We identified known NS1- and NS2-interacting proteins but also uncharacterized proteins, including PACT, an important cofactor for the IFN-I response triggered by the viral RNA-sensor RIG-I. We show here that NS1 binds PACT during virus replication and blocks PACT/RIG-I-mediated activation of IFN-I, which represents a critical event for the host defense. Protein interaction and interference with IFN-I activation depended on the functional integrity of the highly conserved RNA binding domain of NS1. A mutant virus with deletion of NS1 induced high levels of IFN-I in control cells, as expected; in contrast, shRNA-mediated knockdown of PACT compromised IFN-I activation by the mutant virus, but not wild-type virus, a finding consistent with the interpretation that PACT (i) is essential for IAV recognition and (ii) is functionally compromised by NS1. Together, our data describe a novel approach to identify virus-host protein interactions and demonstrate that NS1 interferes with PACT, whose function is critical for robust IFN-I production. IMPORTANCE Influenza A virus (IAV) is an important human pathogen that is responsible for annual epidemics and occasional devastating pandemics. Viral replication and pathogenicity depends on the interference of viral factors with components of the host defense system, particularly the type I interferon (IFN-I) response. The viral NS1 protein is known to counteract virus recognition and IFN-I production, but the molecular mechanism is only partially defined. We used a novel proteomic approach to identify host proteins that are bound by NS1 during virus replication and identified the protein PACT, which had previously been shown to be involved in virus-mediated IFN-I activation. We find that NS1 prevents PACT from interacting with an essential component of the virus recognition pathway, RIG-I, thereby disabling efficient IFN-I production. These observations provide an important piece of information on how IAV efficiently counteracts the host immune defense. PMID:24899174

The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication.

PubMed

Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E; Miorin, Lisa; Johnson, Jeffrey R; Krogan, Nevan J; Basler, Christopher F; Freiberg, Alexander N; Rajsbaum, Ricardo

2017-09-15

Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35 protein contributes to pathogenesis, because it serves as an essential cofactor of the viral polymerase as well as a potent antagonist of innate immunity. However, how VP35 function is regulated by host cellular factors is poorly understood. Here, we report that the host E3-ubiquitin ligase TRIM6 promotes VP35 ubiquitination and is important for efficient virus replication. Therefore, our study identifies a new host factor, TRIM6, as a potential target in the development of antiviral drugs against EBOV. Copyright © 2017 American Society for Microbiology.

The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication

PubMed Central

Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E.; Miorin, Lisa; Johnson, Jeffrey R.; Krogan, Nevan J.; Basler, Christopher F.; Freiberg, Alexander N.

2017-01-01

ABSTRACT Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35 protein contributes to pathogenesis, because it serves as an essential cofactor of the viral polymerase as well as a potent antagonist of innate immunity. However, how VP35 function is regulated by host cellular factors is poorly understood. Here, we report that the host E3-ubiquitin ligase TRIM6 promotes VP35 ubiquitination and is important for efficient virus replication. Therefore, our study identifies a new host factor, TRIM6, as a potential target in the development of antiviral drugs against EBOV. PMID:28679761

Dengue virus life cycle: viral and host factors modulating infectivity.

PubMed

Rodenhuis-Zybert, Izabela A; Wilschut, Jan; Smit, Jolanda M

2010-08-01

Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited dengue fever, an increasing number of patients present more severe manifestations, such as dengue hemorrhagic fever and dengue shock syndrome. In this review we will give an overview of the infectious life cycle of DENV and will discuss the viral and host factors that are important in controlling DENV infection.

Quantitative Proteomic Analysis of Host-virus Interactions Reveals a Role for Golgi Brefeldin A Resistance Factor 1 (GBF1) in Dengue Infection*

PubMed Central

Carpp, Lindsay N.; Rogers, Richard S.; Moritz, Robert L.; Aitchison, John D.

2014-01-01

Dengue virus is considered to be the most important mosquito-borne virus worldwide and poses formidable economic and health care burdens on many tropical and subtropical countries. Dengue infection induces drastic rearrangement of host endoplasmic reticulum membranes into complex membranous structures housing replication complexes; the contribution(s) of host proteins and pathways to this process is poorly understood but is likely to be mediated by protein-protein interactions. We have developed an approach for obtaining high confidence protein-protein interaction data by employing affinity tags and quantitative proteomics, in the context of viral infection, followed by robust statistical analysis. Using this approach, we identified high confidence interactors of NS5, the viral polymerase, and NS3, the helicase/protease. Quantitative proteomics allowed us to exclude a large number of presumably nonspecific interactors from our data sets and imparted a high level of confidence to our resulting data sets. We identified 53 host proteins reproducibly associated with NS5 and 41 with NS3, with 13 of these candidates present in both data sets. The host factors identified have diverse functions, including retrograde Golgi-to-endoplasmic reticulum transport, biosynthesis of long-chain fatty-acyl-coenzyme As, and in the unfolded protein response. We selected GBF1, a guanine nucleotide exchange factor responsible for ARF activation, from the NS5 data set for follow up and functional validation. We show that GBF1 plays a critical role early in dengue infection that is independent of its role in the maintenance of Golgi structure. Importantly, the approach described here can be applied to virtually any organism/system as a tool for better understanding its molecular interactions. PMID:24855065

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

PubMed

Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

Recombinant Protein Expression in Escherichia coli (E.coli): What We Need to Know.

PubMed

Hayat, Seyed Mohammad Gheibi; Farahani, Najmeh; Golichenari, Behrouz; Sahebkar, Amir Hosein

2018-01-31

Host, vector, and culture conditions (including cultivation media) are considered among the three main elements contributing to a successful production of recombinant proteins. Accordingly, one of the most common hosts to produce recombinant therapeutic proteins is Escherichia coli. A comprehensive literature review was performed to identify important factors affecting production of recombinant proteins in Escherichia coli. Escherichia coli is taken into account as the easiest, quickest, and cheapest host with a fully known genome. Thus, numerous modifications have been carried out on Escherichia coli to optimize it as a good candidate for protein expression and; as a result, several engineered strains of Escherichia coli have been designed. In general; host strain, vector, and cultivation parameters are recognized as crucial ones determining success of recombinant protein expression in Escherichia coli. In this review, the role of host, vector, and culture conditions along with current pros and cons of different types of these factors leading to success of recombinant protein expression in Escherichia coli were discussed. Successful protein expression in Escherichia coli necessitates a broad knowledge about physicochemical properties of recombinant proteins, selection among common strains of Escherichia coli and vectors, as well as factors related to media including time, temperature, and inducer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

PubMed Central

Morrot, Alexandre; Villar, Silvina R.; González, Florencia B.; Pérez, Ana R.

2016-01-01

Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease. PMID:27242726

Ontology-based representation and analysis of host-Brucella interactions.

PubMed

Lin, Yu; Xiang, Zuoshuang; He, Yongqun

2015-01-01

Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms. Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host-Brucella interactions and implemented in IDOBRU. Current IDOBRU includes 3611 ontology terms. SPARQL queries identified many results that are critical to the host-Brucella interactions. For example, out of 269 protein virulence factors related to macrophage-Brucella interactions, 81 are critical to Brucella intracellular replication inside macrophages. A SPARQL query also identified 11 biological processes important for Brucella virulence. To systematically represent and analyze fundamental host-pathogen interaction mechanisms, we provided for the first time comprehensive ontological modeling of host-pathogen interactions using Brucella as the pathogen model. The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.

Upregulation of heat shock protein genes by envenomation of ectoparasitoid Bracon hebetor in larval host of Indian meal moth Plodia interpunctella.

PubMed

Shim, Jae-Kyoung; Ha, Dae-Myung; Nho, Si-Kab; Song, Kyung-Sik; Lee, Kyeong-Yeoll

2008-03-01

Effect of envenomation of ectoparasitoid Bracon hebetor was determined on the heart rate and the expression of shsp, hsc70 and hsp90 of the lepidopteran host Plodia interpunctella. Envenomated host larvae were promptly immobilized but heart rate was not changed until 4 days after envenomation. Northern hybridization showed that each hsp gene was differentially influenced by envenomation: continued high induction of shsp, gradual strong induction of hsc70, but no induction of hsp90. Our results suggest that upregulation of both shsp and hsc70 may produce potent factors that have important roles in the mechanism of host-parasitoid relationship.

Leishmania Hijacks Myeloid Cells for Immune Escape

PubMed Central

Martínez-López, María; Soto, Manuel; Iborra, Salvador; Sancho, David

2018-01-01

Protozoan parasites of the Leishmania genus are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious Leishmania species but also on host factors. Recognition of the parasite by host myeloid immune cells is a key to trigger an effective Leishmania-specific immunity. However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to escape host resistance and ensure its transmission. Neutrophils are first in infiltrating infection sites and could act either favoring or protecting against infection, depending on factors such as the genetic background of the host or the parasite species. Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector population involved in parasite clearance. Parasite elimination by macrophages requires the priming and development of an effector Th1 adaptive immunity driven by specific subtypes of dendritic cells. Herein, we will provide a comprehensive outline of how myeloid cells regulate innate and adaptive immunity against Leishmania, and the mechanisms used by the parasites to promote their evasion and sabotage. Understanding the interactions between Leishmania and the host myeloid cells may lead to the development of new therapeutic approaches and improved vaccination to leishmaniases, an important worldwide health problem in which current therapeutic or preventive approaches are limited. PMID:29867798

Sea fan immunity and disease is influenced by metal pollution, host demography, and multiple stressors

NASA Astrophysics Data System (ADS)

Tracy, A. M.; Weil, E.; Harvell, C. D.

2016-02-01

Organisms in natural populations experience an onslaught of stressful conditions that may compromise their ability to fight pathogens, particularly if multiple stressors impact a host at the same time. Environmental stressors can also influence the pathogens. Despite the clear importance of environmental factors for coral host-pathogen interactions and the potential for population-level consequences, there is relatively little research to date on multiple stressors. The population of Caribbean sea fans, Gorgonia ventalina, in Parguera, Puerto Rico is a tractable system in which to study the effects of multiple stressors on two pathogens. Sea fans are dominant members of reefs that provide food and habitat for diverse reef inhabitants. In addition, there is already a foundation of research on sea fan disease and immunity. We first conducted field surveys of 15 sites to assess the effects of demographic and environmental factors on the prevalence and severity of multifocal purple spots (MFPS) and a Labyrinthulid stramenopile pathogen, as well as the host's cellular immune response to each pathogen. We complemented the field survey with a fully factorial, clonally replicated experiment on the separate and combined effects of thermal stress and copper pollution on both the host and the pathogen. Although water quality has been linked to coral disease, there are no studies investigating the role of metal or chemical pollutants, which are high at some of our study sites. Preliminary results show that the sea fan immune response to the Labyrinthulid depends on interactive effects of copper and thermal stress. The field survey identifies colony size as the main driver of MFPS. This in-depth perspective on sea fan disease speaks to the immune capabilities of cnidarians, highlights factors that modify those capabilities, and reflects the complex interaction of host, pathogens, and environment in this ecologically important coral.

Density thresholds for Mopeia virus invasion and persistence in its host Mastomys natalensis.

PubMed

Goyens, J; Reijniers, J; Borremans, B; Leirs, H

2013-01-21

Well-established theoretical models predict host density thresholds for invasion and persistence of parasites with a density-dependent transmission. Studying such thresholds in reality, however, is not obvious because it requires long-term data for several fluctuating populations of different size. We developed a spatially explicit and individual-based SEIR model of Mopeia virus in multimammate mice Mastomys natalensis. This is an interesting model system for studying abundance thresholds because the host is the most common African rodent, populations fluctuate considerably and the virus is closely related to Lassa virus but non-pathogenic to humans so can be studied safely in the field. The simulations show that, while host density clearly is important, sharp thresholds are only to be expected for persistence (and not for invasion), since at short time-spans (as during invasion), stochasticity is determining. Besides host density, also the spatial extent of the host population is important. We observe the repeated local occurrence of herd immunity, leading to a decrease in transmission of the virus, while even a limited amount of dispersal can have a strong influence in spreading and re-igniting the transmission. The model is most sensitive to the duration of the infectious stage, the size of the home range and the transmission coefficient, so these are important factors to determine experimentally in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biochemistry and Molecular Biology of Flaviviruses.

PubMed

Barrows, Nicholas J; Campos, Rafael K; Liao, Kuo-Chieh; Prasanth, K Reddisiva; Soto-Acosta, Ruben; Yeh, Shih-Chia; Schott-Lerner, Geraldine; Pompon, Julien; Sessions, October M; Bradrick, Shelton S; Garcia-Blanco, Mariano A

2018-04-25

Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA-protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

A rhamnose-rich O-antigen mediates adhesion, virulence, and host colonization for the xylem-limited phytopathogen Xylella fastidiosa.

PubMed

Clifford, Jennifer C; Rapicavoli, Jeannette N; Roper, M Caroline

2013-06-01

Xylella fastidiosa is a gram-negative, xylem-limited bacterium that causes a lethal disease of grapevine called Pierce's disease. Lipopolysaccharide (LPS) composes approximately 75% of the outer membrane of gram-negative bacteria and, because it is largely displayed on the cell surface, it mediates interactions between the bacterial cell and its surrounding environment. LPS is composed of a conserved lipid A-core oligosaccharide component and a variable O-antigen portion. By targeting a key O-antigen biosynthetic gene, we demonstrate the contribution of the rhamnose-rich O-antigen to surface attachment, cell-cell aggregation, and biofilm maturation: critical steps for successful infection of the host xylem tissue. Moreover, we have demonstrated that a fully formed O-antigen moiety is an important virulence factor for Pierce's disease development in grape and that depletion of the O-antigen compromises its ability to colonize the host. It has long been speculated that cell-surface polysaccharides play a role in X. fastidiosa virulence and this study confirms that LPS is a major virulence factor for this important agricultural pathogen.

Distribution of intermediate host snails of schistosomiasis and fascioliasis in relation to environmental factors during the dry season in the Tchologo region, Côte d'Ivoire

NASA Astrophysics Data System (ADS)

Krauth, Stefanie J.; Wandel, Nathalie; Traoré, Seïdinan I.; Vounatsou, Penelope; Hattendorf, Jan; Achi, Louise Y.; McNeill, Kristopher; N'Goran, Eliézer K.; Utzinger, Jürg

2017-10-01

Snail-borne trematodiases, such as fascioliasis and schistosomiasis, belong to the neglected tropical diseases; yet, millions of people and livestock are affected. The spatial and temporal distribution of intermediate host snails plays an important role in the epidemiology and control of trematodiases. Snail distribution is influenced by numerous environmental and anthropomorphic factors. The aim of this study was to assess the distribution and constitution of the snail fauna during the dry season in constructed and natural water bodies in the Tchologo region, northern Côte d'Ivoire, and to relate these findings to environmental factors and human infections. Snails were collected using standard procedures and environmental parameters were assessed from a total of 50 water bodies in and around 30 randomly selected villages. A canonical correspondence analysis was performed to establish the relationship between snail occurrence and environmental factors. Furthermore, a total of 743 people from the same 30 villages and nearby settlements were invited for stool and urine examination for the diagnosis of Fasciola spp., Schistosoma haematobium and Schistosoma mansoni. Snails of medical importance of the genera Biomphalaria, Bulinus, Lymnaea and Physa were found. Differences in snail occurrence from sites sampled in December 2014 and snails sampled in February 2015, as well as between the northern and southern part of the study area, were revealed. Various environmental factors, such as temperature and human activities, were related to the occurrence of intermediate host snail species in the region. Only 2.3% of human participants tested positive for schistosomiasis, while no Fasciola eggs were found in stool samples. We conclude that intermediate host snails of Fasciola and Schistosoma co-occur in water bodies in the Tchologo region and that the distribution of these snails correlates not only with environmental factors, but also with the presence of humans and animals and the environmental contamination of their excreta.

Patterns of co-speciation and host switching in primate malaria parasites.

PubMed

Garamszegi, László Zsolt

2009-05-22

The evolutionary history of many parasites is dependent on the evolution of their hosts, leading to an association between host and parasite phylogenies. However, frequent host switches across broad phylogenetic distances may weaken this close evolutionary link, especially when vectors are involved in parasites transmission, as is the case for malaria pathogens. Several studies suggested that the evolution of the primate-infective malaria lineages may be constrained by the phylogenetic relationships of their hosts, and that lateral switches between distantly related hosts may have been occurred. However, no systematic analysis has been quantified the degree of phylogenetic association between primates and their malaria parasites. Here phylogenetic approaches have been used to discriminate statistically between events due to co-divergence, duplication, extinction and host switches that can potentially cause historical association between Plasmodium parasites and their primate hosts. A Bayesian reconstruction of parasite phylogeny based on genetic information for six genes served as basis for the analyses, which could account for uncertainties about the evolutionary hypotheses of malaria parasites. Related lineages of primate-infective Plasmodium tend to infect hosts within the same taxonomic family. Different analyses testing for congruence between host and parasite phylogenies unanimously revealed a significant association between the corresponding evolutionary trees. The most important factor that resulted in this association was host switching, but depending on the parasite phylogeny considered, co-speciation and duplication may have also played some additional role. Sorting seemed to be a relatively infrequent event, and can occur only under extreme co-evolutionary scenarios. The concordance between host and parasite phylogenies is heterogeneous: while the evolution of some malaria pathogens is strongly dependent on the phylogenetic history of their primate hosts, the congruent evolution is less emphasized for other parasite lineages (e.g. for human malaria parasites). Estimation of ancestral states of host use along the phylogenetic tree of parasites revealed that lateral transfers across distantly related hosts were likely to occur in several cases. Parasites cannot infect all available hosts, and they should preferentially infect hosts that provide a similar environment for reproduction. Marginally significant evidence suggested that there might be a consistent variation within host ranges in terms of physiology. The evolution of primate malarias is constrained by the phylogenetic associations of their hosts. Some parasites can preserve a great flexibility to infect hosts across a large phylogenetic distance, thus host switching can be an important factor in mediating host ranges observed in nature. Due to this inherent flexibility and the potential exposure to various vectors, the emergence of new malaria disease in primates including humans cannot be predicted from the phylogeny of parasites.

Food availability affects the strength of mutualistic host–microbiota interactions in Daphnia magna

PubMed Central

Callens, Martijn; Macke, Emilie; Muylaert, Koenraad; Bossier, Peter; Lievens, Bart; Waud, Michael; Decaestecker, Ellen

2016-01-01

The symbiotic gut microbial community is generally known to have a strong impact on the fitness of its host. Nevertheless, it is less clear how the impact of symbiotic interactions on the hosts' fitness varies according to environmental circumstances such as changes in the diet. This study aims to get a better understanding of host–microbiota interactions under different levels of food availability. We conducted experiments with the invertebrate, experimental model organism Daphnia magna and compared growth, survival and reproduction of conventionalized symbiotic Daphnia with germ-free individuals given varying quantities of food. Our experiments revealed that the relative importance of the microbiota for the hosts' fitness varied according to dietary conditions. The presence of the microbiota had strong positive effects on Daphnia when food was sufficient or abundant, but had weaker effects under food limitation. Our results indicate that the microbiota can be a potentially important factor in determining host responses to changes in dietary conditions. Characterization of the host-associated microbiota further showed that Aeromonas sp. was the most prevalent taxon in the digestive tract of Daphnia. PMID:26405832

Incidence of Facultative Bacterial Endosymbionts in Spider Mites Associated with Local Environments and Host Plants.

PubMed

Zhu, Yu-Xi; Song, Yue-Ling; Zhang, Yan-Kai; Hoffmann, Ary A; Zhou, Jin-Cheng; Sun, Jing-Tao; Hong, Xiao-Yue

2018-03-15

Spider mites are frequently associated with multiple endosymbionts whose infection patterns often exhibit spatial and temporal variation. However, the association between endosymbiont prevalence and environmental factors remains unclear. Here, we surveyed endosymbionts in natural populations of the spider mite, Tetranychus truncatus , in China, screening 935 spider mites from 21 localities and 12 host plant species. Three facultative endosymbiont lineages, Wolbachia , Cardinium , and Spiroplasma , were detected at different infection frequencies (52.5%, 26.3%, and 8.6%, respectively). Multiple endosymbiont infections were observed in most local populations, and the incidence of individuals with the Wolbachia - Spiroplasma coinfection was higher than expected from the frequency of each infection within a population. Endosymbiont infection frequencies exhibited associations with environmental factors: Wolbachia infection rates increased at localities with higher annual mean temperatures, while Cardinium and Spiroplasma infection rates increased at localities from higher altitudes. Wolbachia was more common in mites from Lycopersicon esculentum and Glycine max compared to those from Zea mays This study highlights that host-endosymbiont interactions may be associated with environmental factors, including climate and other geographically linked factors, as well as the host's food plant. IMPORTANCE The aim of this study was to examine the incidence of endosymbiont distribution and the infection patterns in spider mites. The main findings are that multiple endosymbiont infections were more common than expected and that endosymbiont infection frequencies were associated with environmental factors. This work highlights that host-endosymbiont interactions need to be studied within an environmental and geographic context. Copyright © 2018 American Society for Microbiology.

Modelling the effects of phylogeny and body size on within-host pathogen replication and immune response.

PubMed

Banerjee, Soumya; Perelson, Alan S; Moses, Melanie

2017-11-01

Understanding how quickly pathogens replicate and how quickly the immune system responds is important for predicting the epidemic spread of emerging pathogens. Host body size, through its correlation with metabolic rates, is theoretically predicted to impact pathogen replication rates and immune system response rates. Here, we use mathematical models of viral time courses from multiple species of birds infected by a generalist pathogen (West Nile Virus; WNV) to test more thoroughly how disease progression and immune response depend on mass and host phylogeny. We use hierarchical Bayesian models coupled with nonlinear dynamical models of disease dynamics to incorporate the hierarchical nature of host phylogeny. Our analysis suggests an important role for both host phylogeny and species mass in determining factors important for viral spread such as the basic reproductive number, WNV production rate, peak viraemia in blood and competency of a host to infect mosquitoes. Our model is based on a principled analysis and gives a quantitative prediction for key epidemiological determinants and how they vary with species mass and phylogeny. This leads to new hypotheses about the mechanisms that cause certain taxonomic groups to have higher viraemia. For example, our models suggest that higher viral burst sizes cause corvids to have higher levels of viraemia and that the cellular rate of virus production is lower in larger species. We derive a metric of competency of a host to infect disease vectors and thereby sustain the disease between hosts. This suggests that smaller passerine species are highly competent at spreading the disease compared with larger non-passerine species. Our models lend mechanistic insight into why some species (smaller passerine species) are pathogen reservoirs and some (larger non-passerine species) are potentially dead-end hosts for WNV. Our techniques give insights into the role of body mass and host phylogeny in the spread of WNV and potentially other zoonotic diseases. The major contribution of this work is a computational framework for infectious disease modelling at the within-host level that leverages data from multiple species. This is likely to be of interest to modellers of infectious diseases that jump species barriers and infect multiple species. Our method can be used to computationally determine the competency of a host to infect mosquitoes that will sustain WNV and other zoonotic diseases. We find that smaller passerine species are more competent in spreading the disease than larger non-passerine species. This suggests the role of host phylogeny as an important determinant of within-host pathogen replication. Ultimately, we view our work as an important step in linking within-host viral dynamics models to between-host models that determine spread of infectious disease between different hosts. © 2017 The Author(s).

The Benefit of Additional Oviposition Targets for a Polyphagous Butterfly

PubMed Central

Johansson, Josefin; Bergström, Anders; Janz, Niklas

2007-01-01

While the reasons for the prevalence of specialists over generalists among herbivorous insects have been at the focus of much interest, less effort has been put into understanding the polyphagous exceptions. Recent studies have suggested that these exceptions may be important for insect diversification, which calls for a better understanding of the potential factors that can lead to an increased host plant repertoire. Females of the Nymphalid butterfly, Polygonia c-album, were used to test if egg output and/or likelihood of finding a host increased with the addition of a secondary host. There was no effect of prior eggs on the host for willingness to oviposit on a plant. The main experiments were conducted both in small laboratory cages and in large outdoor experimental arenas. No positive effect was found when another oviposition target was added in small cages in the laboratory. On the other hand, in the outdoor arenas the females more often found a host to oviposit on and had a higher egg output when they had access to an additional host, even though the second host was lower in their preference hierarchy. The difference between these experiments was attributed to searching for acceptable host plants within a patch, a factor that was included in the large cages but not in the small. When host availability is limited, adding oviposition targets can potentially act to counterbalance specialization and thus favor the evolution of generalization. PMID:20334600

Comparative Characterization of the Sindbis Virus Proteome from Mammalian and Invertebrate Hosts Identifies nsP2 as a Component of the Virus Nucleocapsid and Sorting Nexin 5 as a Significant Host Factor for Alphavirus Replication.

PubMed

Schuchman, Ryan; Kilianski, Andy; Piper, Amanda; Vancini, Ricardo; Ribeiro, José M C; Sprague, Thomas R; Nasar, Farooq; Boyd, Gabrielle; Hernandez, Raquel; Glaros, Trevor

2018-05-09

Recent advances in mass spectrometry methods and instrumentation now allow for more accurate identification of proteins in low abundance. This technology was applied to Sindbis virus, the prototypical alphavirus to investigate the viral proteome. To determine if host proteins are specifically packaged into alphavirus virions, Sindbis virus (SINV) was grown in multiple host cells representing vertebrate and mosquito hosts and total protein content of purified virions was determined. This analysis identified host factors not previously associated with alphavirus entry, replication, or egress. One host protein, sorting nexin 5 (SNX5), was shown to be critical for the replication of three different alphaviruses, Sindbis, Mayaro and Chikungunya virus. The most significant finding was that in addition to the host proteins, SINV non-structural protein 2 (nsP2) was detected within virions grown in all host cells examined. The protein and RNA-interacting capabilities of nsP2 coupled with its presence in the virion support a role for nsP2 during packaging and/or entry of progeny virus. This function has not been identified for this protein. Taken together, this strategy identified at least one host factor integrally involved in alphavirus replication. Identification of other host proteins provides insight into alphavirus-host interactions during viral replication in both vertebrate and invertebrate hosts. This method of virus proteome analysis may also be useful for the identification of protein candidates for host-based therapeutics. IMPORTANCE Pathogenic Alphaviruses, such as Chikungunya and Mayaro virus, continue to plague public health in developing and developed countries alike. Alphaviruses belong to a group of viruses vectored in nature by hematophagous (blood-feeding) insects and are termed Arboviruses (arthropod-borne viruses). This group of viruses contains many human pathogens such as dengue fever, West Nile and Yellow fever viruses. With few exceptions there are no vaccines or prophylactics for these agents leaving one third of the world population at risk of infection. Identifying effective antivirals has been a long term goal for combating these diseases not only because of the lack of vaccines but also because they are effective during an ongoing epidemic. Mass spectrometry-based analysis of the Sindbis virus proteome can be effective in identifying host genes involved in virus replication and novel functions for virus proteins. Identification of these factors is invaluable for the prophylaxis of this group of viruses. Copyright © 2018 Schuchman et al.

Why Great Britain's success in Beijing could have been anticipated and why it should continue beyond 2012.

PubMed

Nevill, A M; Balmer, N J; Winter, E M

2009-12-01

Home advantage in the summer Olympic Games is well known. What is not so well known is that countries that host the Olympic Games perform better in the games before and after the games in which they were hosts. To model/quantify the significance associated with these "hosting" effects and to explain the likely causes of Great Britain's improved medals haul in Beijing, while examining implications for London 2012 and beyond. Using all hosting cities/countries since World War II and analysing the number of medals awarded to competitors as a binomial proportion (p) response variable within a logit model, we identified a significant increase in the probability/odds of a country obtaining a medal in the Olympic Games before, during and after hosting the Olympics. Funding appears to be an important factor when explaining these findings. Almost all countries that have been awarded the games after World War II would appear to have invested heavily in sport before being awarded the games. A second factor in Great Britain's success is the legacy of hosting the Commonwealth Games in 2002 (a post-hosting games effect) that undoubtedly provided an infrastructure that benefited, in particular, cycling. Whether the International Olympics Committee either consciously or subconsciously take these factors into account is unclear when awarding the games to a city. What is clear is that based on these findings, Great Britain's prospects of maintaining the Olympic success achieved in Beijing is likely to continue to London 2012 and beyond.

Symbiotic factors in Burkholderia essential for establishing an association with the bean bug, Riptortus pedestris.

PubMed

Kim, Jiyeun Kate; Lee, Bok Luel

2015-01-01

Symbiotic bacteria are common in insects and intimately affect the various aspects of insect host biology. In a number of insect symbiosis models, it has been possible to elucidate the effects of the symbiont on host biology, whereas there is a limited understanding of the impact of the association on the bacterial symbiont, mainly due to the difficulty of cultivating insect symbionts in vitro. Furthermore, the molecular features that determine the establishment and persistence of the symbionts in their host (i.e., symbiotic factors) have remained elusive. However, the recently established model, the bean bug Riptortus pedestris, provides a good opportunity to study bacterial symbiotic factors at a molecular level through their cultivable symbionts. Bean bugs acquire genus Burkholderia cells from the environment and harbor them as gut symbionts in the specialized posterior midgut. The genome of the Burkholderia symbiont was sequenced, and the genomic information was used to generate genetically manipulated Burkholderia symbiont strains. Using mutant symbionts, we identified several novel symbiotic factors necessary for establishing a successful association with the host gut. In this review, these symbiotic factors are classified into three categories based on the colonization dynamics of the mutant symbiont strains: initiation, accommodation, and persistence factors. In addition, the molecular characteristics of the symbiotic factors are described. These newly identified symbiotic factors and on-going studies of the Riptortus-Burkholderia symbiosis are expected to contribute to the understanding of the molecular cross-talk between insects and bacterial symbionts that are of ecological and evolutionary importance. © 2014 Wiley Periodicals, Inc.

Integration host factor is important for biofilm formation by Salmonella enterica Enteritidis.

PubMed

Leite, Bruna; Werle, Catierine Hirsch; Carmo, Camila Pinheiro do; Nóbrega, Diego Borin; Milanez, Guilherme Paier; Culler, Hebert Fabricio; Sircili, Marcelo Palma; Alvarez-Martinez, Cristina E; Brocchi, Marcelo

2017-08-31

Salmonella enterica Enteritidis forms biofilms and survives in agricultural environments, infecting poultry and eggs. Bacteria in biofilms are difficult to eradicate compared to planktonic cells, causing serious problems in industry and public health. In this study, we evaluated the role of ihfA and ihfB in biofilm formation by S. enterica Enteritidis by employing different microbiology techniques. Our data indicate that ihf mutant strains are impaired in biofilm formation, showing a reduction in matrix formation and a decrease in viability and metabolic activity. Phenotypic analysis also showed that deletion of ihf causes a deficiency in curli fimbriae expression, cellulose production and pellicle formation. These results show that integration host factor has an important regulatory role in biofilm formation by S. enterica Enteritidis. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Gills of Reef Fish Support a Distinct Microbiome Influenced by Host-Specific Factors.

PubMed

Pratte, Zoe A; Besson, Marc; Hollman, Rebecca D; Stewart, Frank J

2018-05-01

Teleost fish represent the most diverse of the vertebrate groups and play important roles in food webs, as ecosystem engineers, and as vectors for microorganisms. However, the microbial ecology of fishes remains underexplored for most host taxa and for certain niches on the fish body. This is particularly true for the gills, the key sites of respiration and waste exchange in fishes. Here we provide a comprehensive analysis of the gill microbiome. We focus on ecologically diverse taxa from coral reefs around Moorea, sampling the gills and intestines of adults and juveniles representing 15 families. The gill microbiome composition differed significantly from that of the gut for both adults and juveniles, with fish-associated niches having lower alpha diversity values and higher beta diversity values than those for seawater, sediment, and alga-associated microbiomes. Of ∼45,000 operational taxonomic units (OTUs) detected across all samples, 11% and 13% were detected only in the gill and the intestine, respectively. OTUs most enriched in the gill included members of the gammaproteobacterial genus Shewanella and the family Endozoicimonaceae In adult fish, both gill and intestinal microbiomes varied significantly among host species grouped by diet category. Gill and intestinal microbiomes from the same individual were more similar to one another than to gill and intestinal microbiomes from different individuals. These results demonstrate that distinct body sites are jointly influenced by host-specific organizing factors operating at the level of the host individual. The results also identify taxonomic signatures unique to the gill and the intestine, confirming fish-associated niches as distinct reservoirs of marine microbial diversity. IMPORTANCE Fish breathe and excrete waste through their gills. The gills are also potential sites of pathogen invasion and colonization by other microbes. However, we know little about the microbial communities that live on the gill and the factors shaping their diversity. Focusing on ecologically distinct types of coral reef fish, we provide a comprehensive analysis of the fish gill microbiome. By comparison to microbiomes of the gut and the surrounding environment, we identify microbes unique to the gill niche. These microbes may be targets for further studies to determine the contribution of the microbiome to waste exchange or host immunity. We also show that despite exhibiting a unique taxonomic signature, the gill microbiome is influenced by factors that also influence the gut microbiome. These factors include the specific identity of the host individual. These results suggest basic principles describing how association with fishes structures the composition of microbial communities. Copyright © 2018 American Society for Microbiology.

Differential expression of growth factors at the cellular level in virus-infected brain

PubMed Central

Prosniak, Mikhail; Zborek, Anna; Scott, Gwen S.; Roy, Anirban; Phares, Timothy W.; Koprowski, Hilary; Hooper, D. Craig

2003-01-01

The contribution of host factors to rabies virus (RV) transcription/replication and axonal/transsynaptic spread is largely unknown. We previously identified several host genes that are up-regulated in the mouse brain during RV infection, including neuroleukin, which is involved in neuronal growth and survival, cell motility, and differentiation, and fibroblast growth factor homologous factor 4 (FHF4), which has been implicated in limb and nervous system development. In this study, we used real-time quantitative RT-PCR to assess the expression of mRNAs specific for neuroleukin, the two isoforms of FHF4 (FHF4-1a and -1b) encoded by the FHF4 gene, and N protein of RV in neurons and astrocytes isolated by laser capture microdissection from mouse brains infected with the laboratory-adapted RV strain CVS-N2c or with a street RV of silver-haired bat origin. Differences in the gene expression patterns suggest that the capacity of RV strains to infect nonneuronal cells and differentially modulate host gene expression may be important in virus replication and spread in the CNS. PMID:12736376

Visualizing the Effects of Sputum on Biofilm Development Using a Chambered Coverglass Model.

PubMed

Beaudoin, Trevor; Kennedy, Sarah; Yau, Yvonne; Waters, Valerie

2016-12-14

Biofilms consist of groups of bacteria encased in a self-secreted matrix. They play an important role in industrial contamination as well as in the development and persistence of many health related infections. One of the most well described and studied biofilms in human disease occurs in chronic pulmonary infection of cystic fibrosis patients. When studying biofilms in the context of the host, many factors can impact biofilm formation and development. In order to identify how host factors may affect biofilm formation and development, we used a static chambered coverglass method to grow biofilms in the presence of host-derived factors in the form of sputum supernatants. Bacteria are seeded into chambers and exposed to sputum filtrates. Following 48 hr of growth, biofilms are stained with a commercial biofilm viability kit prior to confocal microscopy and analysis. Following image acquisition, biofilm properties can be assessed using different software platforms. This method allows us to visualize key properties of biofilm growth in presence of different substances including antibiotics.

Impact of Leishmania metalloprotease GP63 on macrophage signaling

PubMed Central

Isnard, Amandine; Shio, Marina T.; Olivier, Martin

2012-01-01

The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

Impact of Leishmania metalloprotease GP63 on macrophage signaling.

PubMed

Isnard, Amandine; Shio, Marina T; Olivier, Martin

2012-01-01

The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions.

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli

PubMed Central

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B. Brett; So, Yee Wing; Stothard, Paul

2017-01-01

ABSTRACT Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota. PMID:28667114

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli.

PubMed

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B Brett; So, Yee Wing; Stothard, Paul; Willing, Benjamin P

2017-09-01

Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota. Copyright © 2017 American Society for Microbiology.

Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice.

PubMed

Bongers, Gerold; Pacer, Michelle E; Geraldino, Thais H; Chen, Lili; He, Zhengxiang; Hashimoto, Daigo; Furtado, Glaucia C; Ochando, Jordi; Kelley, Kevin A; Clemente, Jose C; Merad, Miriam; van Bakel, Harm; Lira, Sergio A

2014-03-10

The preferential localization of some neoplasms, such as serrated polyps (SPs), in specific areas of the intestine suggests that nongenetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB-EGF throughout the intestine but developed SPs only in the cecum. Here we show that a host-specific microbiome was associated with SPs and that alterations of the microbiota induced by antibiotic treatment or by embryo transfer rederivation markedly inhibited the formation of SPs in the cecum. Mechanistically, development of SPs was associated with a local decrease in epithelial barrier function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-α, and IL-1. Increased numbers of neutrophils were found within the SPs, and their depletion significantly reduced polyp growth. Together these results indicate that nongenetic factors contribute to the development of SPs and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota.

Grain dust and the lungs.

PubMed Central

Chan-Yeung, M.; Ashley, M. J.; Grzybowski, S.

1978-01-01

Grain dust is composed of a large number of materials, including various types of grain and their disintegration products, silica, fungi, insects and mites. The clinical syndromes described in relation to exposure to grain dust are chronic bronchitis, grain dust asthma, extrinsic allergic alveolitis, grain fever and silo-filler's lung. Rhinitis and conjunctivitis are also common in grain workers. While the concentration and the quality of dust influence the frequency and the type of clinical syndrome in grain workers, host factors are also important. Of the latter, smoking is the most important factor influencing the frequency of chronic bronchitis. The role of atopy and of bronchial hyperreactivity in grain dust asthma has yet to be assessed. Several well designed studies are currently being carried out in North America not only to delineate the frequency of the respiratory abnormalities, the pathogenetic mechanisms and the host factors, but also to establish a meaningful threshold limit concentration for grain dust. Images p1272-a PMID:348288

Identification of novel secreted virulence factors from Xylella fastidiosa using a TRV expression system

USDA-ARS?s Scientific Manuscript database

Xylella fastidiosa is a bacterium that causes leaf scorch diseases of agriculturally important crops including grapevines and almonds. Little is known about virulence factors that are necessary for X. fastidiosa to grow and cause disease in the xylem vessels of a plant host. Any protein secreted by ...

Non-Crop Host Sampling Yields Insights into Small-Scale Population Dynamics of Drosophila suzukii (Matsumura)

PubMed Central

Loeb, Gregory M.

2018-01-01

Invasive, polyphagous crop pests subsist on a number of crop and non-crop resources. While knowing the full range of host species is important, a seasonal investigation into the use of non-crop plants adjacent to cropping systems provide key insights into some of the factors determining local population dynamics. This study investigated the infestation of non-crop plants by the invasive Drosophila suzukii (Matsumura), a pest of numerous economically important stone and small fruit crops, by sampling fruit-producing non-crop hosts adjacent to commercial plantings weekly from June through November in central New York over a two-year period. We found D. suzukii infestation rates (number of flies emerged/kg fruit) peaked mid-August through early September, with Rubus allegheniensis Porter and Lonicera morrowii Asa Gray showing the highest average infestation in both years. Interannual infestation patterns were similar despite a lower number of adults caught in monitoring traps the second year, suggesting D. suzukii host use may be density independent. PMID:29301358

The origin and radiation of Macaronesian beetles breeding in Euphorbia: the relative importance of multiple data partitions and population sampling.

PubMed

Jordal, Bjarte H; Hewitt, Godfrey M

2004-10-01

Species-level phylogenies derived from many independent character sources and wide geographical sampling provide a powerful tool in assessing the importance of various factors associated with cladogenesis. In this study, we explore the relative importance of insular isolation and host plant switching in the diversification of a group of bark beetles (Curculionidae: Scolytinae) feeding and breeding in woody Euphor biaspurges. All species in the genus Aphanarthrumare each associated with only one species group of Euphorbia(succulents or one of three different arborescent groups), and the majority of species are endemic to one or several of the Macaronesian Islands. Hence, putative mechanisms of speciation could be assessed by identifying pairs of sister species in a phylogenetic analysis. We used DNA sequences from two nuclear and two mitochondrial genes, and morphological characters, to reconstruct the genealogical relationships among 92 individuals of 25 species and subspecies of Aphanarthrumand related genera. A stable tree topology was highly dependent on multiple character sources, but much less so on wide population sampling. However, multiple samples per species demonstrated one case of species paraphyly, as well as deep coalescence among three putative subspecies pairs. The phylogenetic analyses consistently placed the arborescent breeding and West African--Lanzarote-distributed species A. armatumin the most basal position in Aphanarthrum, rendering this genus paraphyletic with respect to Coleobothrus. Two major radiations followed, one predominantly African lineage of succulent feeding species, and one island radiation associated with arborescent host plants. Sister comparisons showed that most recent divergences occurred in allopatry on closely related hosts, with subsequent expansions obscuring more ancient events. Only 6 out of 24 cladogenetic events were associated with host switching, rendering geographical factors more important in recent diversification.

Factors affecting host range in a generalist seed pathogen of semi-arid shrublands

Treesearch

Julie Beckstead; Susan E. Meyer; Kurt O. Reinhart; Kellene M. Bergen; Sandra R. Holden; Heather F. Boekweg

2014-01-01

Generalist pathogens can exhibit differential success on different hosts, resulting in complex host range patterns. Several factors operate to reduce realized host range relative to potential host range, particularly under field conditions. We explored factors influencing host range of the naturally occurring generalist ascomycete grass seed pathogen Pyrenophora...

Ecomorphology of parasite attachment: experiments with feather lice.

PubMed

Bush, Sarah E; Sohn, Edward; Clayton, Dale H

2006-02-01

The host specificity of some parasites can be reinforced by morphological specialization for attachment to mobile hosts. For example, ectoparasites with adaptations for attaching to hosts of a particular size might not be able to remain attached to larger or smaller hosts. This hypothesis is suggested by the positive correlation documented between the body sizes of many parasites and their hosts. We adopted an ecomorphological approach to test the attachment hypothesis. We tested the ability of host-specific feather lice (Phthiraptera: Ischnocera) to attach to 6 novel species of pigeons and doves that vary in size by nearly 2 orders of magnitude. Surprisingly, Rock Pigeon lice (Columbicola columbae) remained attached equally well to all 6 novel host species. We tested the relative importance of 3 factors that could facilitate louse attachment: whole-body insertion, tarsal claw use, and mandible use. Insertion, per se, was not necessary for attachment. However, insertion on coarse feathers of large hosts allowed lice to access feather barbules with their mandibles. Mandible use was a key component of attachment regardless of feather size. Attachment constraints do not appear to reinforce host specificity in this system.

Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2.

PubMed

McCune, Broc T; Tang, Wei; Lu, Jia; Eaglesham, James B; Thorne, Lucy; Mayer, Anne E; Condiff, Emily; Nice, Timothy J; Goodfellow, Ian; Krezel, Andrzej M; Virgin, Herbert W

2017-07-11

The Norovirus genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail. VAPA was required for the efficiency of a step(s) in the viral replication cycle after entry of viral RNA into the cytoplasm but before the synthesis of viral minus-sense RNA. The interaction of VAPA with viral NS1/2 proteins is conserved between murine and human noroviruses. Murine norovirus NS1/2 directly bound the major sperm protein (MSP) domain of VAPA through its NS1 domain. Mutations within NS1 that disrupted interaction with VAPA inhibited viral replication. Structural analysis revealed that the viral NS1 domain contains a mimic of the phenylalanine-phenylalanine-acidic-tract (FFAT) motif that enables host proteins to bind to the VAPA MSP domain. The NS1/2-FFAT mimic region interacted with the VAPA-MSP domain in a manner similar to that seen with bona fide host FFAT motifs. Amino acids in the FFAT mimic region of the NS1 domain that are important for viral replication are highly conserved across murine norovirus strains. Thus, VAPA interaction with a norovirus protein that functionally mimics host FFAT motifs is important for murine norovirus replication. IMPORTANCE Human noroviruses are a leading cause of gastroenteritis worldwide, but host factors involved in norovirus replication are incompletely understood. Murine noroviruses have been studied to define mechanisms of norovirus replication. Here we defined the importance of the interaction between the hitherto poorly studied NS1/2 norovirus protein and the VAPA host protein. The NS1/2-VAPA interaction is conserved between murine and human noroviruses and was important for early steps in murine norovirus replication. Using structure-function analysis, we found that NS1/2 contains a short sequence that molecularly mimics the FFAT motif that is found in multiple host proteins that bind VAPA. This represents to our knowledge the first example of functionally important mimicry of a host FFAT motif by a microbial protein. Copyright © 2017 McCune et al.

A Zinc-Finger-Family Transcription Factor, AbVf19, Is Required for the Induction of a Gene Subset Important for Virulence in Alternaria brassicicola

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Akhil; Ohm, Robin A.; Oxiles, Lindsay

2011-10-26

Alternaria brassicicola is a successful saprophyte and necrotrophic plant pathogen with a broad host range within the family Brassicaceae. It produces secondary metabolites that marginally affect virulence. Cell wall degrading enzymes (CDWE) have been considered important for pathogenesis but none of them individually have been identified as significant virulence factors in A. brassicicola. In this study, knockout mutants of a gene, AbVf19, were created and produced considerably smaller lesions than the wild type on inoculated host plants. The presence of tandem zinc-finger domains in the predicted amino acid sequence and nuclear localization of AbVf19- reporter protein suggested that it wasmore » a transcription factor. Gene expression comparisons using RNA-seq identified 74 genes being downregulated in the mutant during a late stage of infection. Among the 74 downregulated genes, 28 were putative CWDE genes. These were hydrolytic enzyme genes that composed a small fraction of genes within each family of cellulases, pectinases, cutinases, and proteinases. The mutants grew slower than the wild type on an axenic medium with pectin as a major carbon source. This study demonstrated the existence and the importance of a transcription factor that regulates a suite of genes that are important for decomposing and utilizing plant material during the late stage of plant infection.« less

Eastern equine encephalomyelitis

USGS Publications Warehouse

Hansen, W.; Docherty, D.E.

1999-01-01

Eastern equine encephalitis (EEE) is caused by infection with an RNA virus classified in the family Togaviridae. The virus is also referred to as an “arbovirus” because virus replication takes place within mosquitoes that then transmit the disease agent to vertebrate hosts such as birds and mammals, including humans. The term arbovirus is shortened nomenclature for arthropod (insect) borne (transmitted) viruses. Culiseta melanura is the most important mosquito vector; it silently (no disease) transmits and maintains the virus among birds. However, several other mosquito species can transmit this virus, including the introduced Asian tiger mosquito. New hosts become infected when they enter this endemic natural cycle and are fed upon by an infected mosquito. Therefore, the presence of mosquito habitat, the feeding habits of different mosquito species, and the activity patterns of vertebrate hosts are among the important factors for disease transmission.

Effects of predation stress and food ration on perch gut microbiota.

PubMed

Zha, Yinghua; Eiler, Alexander; Johansson, Frank; Svanbäck, Richard

2018-02-06

Gut microbiota provide functions of importance to influence hosts' food digestion, metabolism, and protection against pathogens. Factors that affect the composition and functions of gut microbial communities are well studied in humans and other animals; however, we have limited knowledge of how natural food web factors such as stress from predators and food resource rations could affect hosts' gut microbiota and how it interacts with host sex. In this study, we designed a two-factorial experiment exposing perch (Perca fluviatilis) to a predator (pike, Esox lucius), and different food ratios, to examine the compositional and functional changes of perch gut microbiota based on 16S rRNA amplicon sequencing. We also investigated if those changes are host sex dependent. We showed that overall gut microbiota composition among individual perch significantly responded to food ration and predator presence. We found that species richness decreased with predator presence, and we identified 23 taxa from a diverse set of phyla that were over-represented when a predator was present. For example, Fusobacteria increased both at the lowest food ration and at predation stress conditions, suggesting that Fusobacteria are favored by stressful situations for the host. In concordance, both food ration and predation stress seemed to influence the metabolic repertoire of the gut microbiota, such as biosynthesis of other secondary metabolites, metabolism of cofactors, and vitamins. In addition, the identified interaction between food ration and sex emphasizes sex-specific responses to diet quantity in gut microbiota. Collectively, our findings emphasize an alternative state in gut microbiota with responses to changes in natural food webs depending on host sex. The obtained knowledge from this study provided us with an important perspective on gut microbiota in a food web context.

Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease.

PubMed

Miftahussurur, Muhammad; Yamaoka, Yoshio

2015-01-01

Helicobacter pylori infection plays an important role in the pathogenesis of peptic ulcer disease (PUD). Several factors have been proposed as possible H. pylori virulence determinants; for example, bacterial adhesins and gastric inflammation factors are associated with an increased risk of PUD. However, differences in bacterial virulence factors alone cannot explain the opposite ends of the PUD disease spectrum, that is duodenal and gastric ulcers; presumably, both bacterial and host factors contribute to the differential response. Carriers of the high-producer alleles of the pro-inflammatory cytokines IL-1B, IL-6, IL-8, IL-10, and TNF-α who also carry low-producer allele of anti-inflammatory cytokines have severe gastric mucosal inflammation, whereas carriers of the alternative alleles have mild inflammation. Recent reports have suggested that the PSCA and CYP2C19 ultra-rapid metabolizer genotypes are also associated with PUD.

Final Technical Report to proposal DE-FG02-95ER20187

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dangl, Jeff

Our long term aim over our many years of generous DOE-BES funding was to understand mechanisms by which the pathogen virulence factors (called ‘type III effectors’) AvrRpm1 and AvrB activate the plant NLR immune receptor RPM1. In general effectors are delivered from the infecting bacteria into host cells by the type III pilus, where they manipulate host machinery to help pathogens overcome host defense. Delivery of effectors to increase virulence is a general feature of all classes of plant pathogens, from fungi to insects to oomcyetes and bacteria. Hence, understanding the overall diversity of effectors, their myriad delivery systems andmore » their effectors on host cell biology, is of central importance in plant immunology.« less

Helminths community of veterinary importance of livestock in relation to some ecological and biological factors.

PubMed

Ibrahim, Mohamed M; Ghamdi, Manea; Gahmdi, Mesfer

2008-01-01

The goals of this study were: (I) to report the helminth population in cattle, sheep and goats; (II) to determine the concentration and diversity of the population; and (III) to study the role of host age, host sex, diet and season in structuring the population. A total of 485 cattle, 1144 sheep and 989 goats were examined for helminth population for four seasons. The helminth population consisted of nine species, four trematodes, four cestodes and one nematode. The overall infection prevalence in cattle, sheep and goats was 12.92%, 18.63% and 13.45%, respectively. Echinococcus granulosus was the most prevalent parasite. The overall mean species concentration per host was 1.23, 0.95 and 0.53 in cattle, sheep and goats, respectively. Species concentration, prevalence and mean abundance varied significantly in relation to host age, sex, diet and season. In conclusion, the influence of the factors investigated on structuring the helminth population of livestock, varied from species to another. We cannot say if the low species concentration and the recorded infection rates observed in the present study are typical of the host species or if they are due to characteristics of the study area, since there is no data available for other host populations.

The Influence of the Host Plant Is the Major Ecological Determinant of the Presence of Nitrogen-Fixing Root Nodule Symbiont Cluster II Frankia Species in Soil

PubMed Central

Battenberg, Kai; Wren, Jannah A.; Hillman, Janell; Edwards, Joseph; Huang, Liujing

2016-01-01

ABSTRACT The actinobacterial genus Frankia establishes nitrogen-fixing root nodule symbioses with specific hosts within the nitrogen-fixing plant clade. Of four genetically distinct subgroups of Frankia, cluster I, II, and III strains are capable of forming effective nitrogen-fixing symbiotic associations, while cluster IV strains generally do not. Cluster II Frankia strains have rarely been detected in soil devoid of host plants, unlike cluster I or III strains, suggesting a stronger association with their host. To investigate the degree of host influence, we characterized the cluster II Frankia strain distribution in rhizosphere soil in three locations in northern California. The presence/absence of cluster II Frankia strains at a given site correlated significantly with the presence/absence of host plants on the site, as determined by glutamine synthetase (glnA) gene sequence analysis, and by microbiome analysis (16S rRNA gene) of a subset of host/nonhost rhizosphere soils. However, the distribution of cluster II Frankia strains was not significantly affected by other potential determinants such as host-plant species, geographical location, climate, soil pH, or soil type. Rhizosphere soil microbiome analysis showed that cluster II Frankia strains occupied only a minute fraction of the microbiome even in the host-plant-present site and further revealed no statistically significant difference in the α-diversity or in the microbiome composition between the host-plant-present or -absent sites. Taken together, these data suggest that host plants provide a factor that is specific for cluster II Frankia strains, not a general growth-promoting factor. Further, the factor accumulates or is transported at the site level, i.e., beyond the host rhizosphere. IMPORTANCE Biological nitrogen fixation is a bacterial process that accounts for a major fraction of net new nitrogen input in terrestrial ecosystems. Transfer of fixed nitrogen to plant biomass is especially efficient via root nodule symbioses, which represent evolutionarily and ecologically specialized mutualistic associations. Frankia spp. (Actinobacteria), especially cluster II Frankia spp., have an extremely broad host range, yet comparatively little is known about the soil ecology of these organisms in relation to the host plants and their rhizosphere microbiomes. This study reveals a strong influence of the host plant on soil distribution of cluster II Frankia spp. PMID:27795313

Distributional Patterns of Pseudacteon Associated with the Solenopsis saevissima Complex in South America

PubMed Central

Patrock, Richard J. W.; Porter, Sanford D.; Gilbert, Lawrence E.; Folgarait, Patricia J.

2009-01-01

Classical biological control efforts against imported fire ants have largely involved the use of Pseudacteon parasitoids. To facilitate further exploration for species and population biotypes a database of collection records for Pseudacteon species was organized, including those from the literature and other sources. These data were then used to map the geographical ranges of species associated with the imported fire ants in their native range in South America. In addition, we found geographical range metrics for all species in the genus and related these metrics to latitude and host use. Approximately equal numbers of Pseudacteon species were found in temperate and tropical regions, though the majority of taxa found only in temperate areas were found in the Northern Hemisphere. No significant differences in sizes of geographical ranges were found between Pseudacteon associated with the different host complexes of fire ants despite the much larger and systemic collection effort associated with the S. saevissima host group. The geographical range of the flies was loosely associated with both the number of hosts and the geographical range of their hosts. Pseudacteon with the most extensive ranges had either multiple hosts or hosts with broad distributions. Mean species richnesses of Pseudacteon in locality species assemblages associated with S. saevissima complex ants was 2.8 species, but intensively sampled locations were usually much higher. Possible factors are discussed related to variation in the size of geographical range, and areas in southern South America are outlined that are likely to have been under-explored for Pseudacteon associated with imported fire ants. PMID:20050779

The saliva microbiome of Pan and Homo

PubMed Central

2013-01-01

Background It is increasingly recognized that the bacteria that live in and on the human body (the microbiome) can play an important role in health and disease. The composition of the microbiome is potentially influenced by both internal factors (such as phylogeny and host physiology) and external factors (such as diet and local environment), and interspecific comparisons can aid in understanding the importance of these factors. Results To gain insights into the relative importance of these factors on saliva microbiome diversity, we here analyze the saliva microbiomes of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) from two sanctuaries in Africa, and from human workers at each sanctuary. The saliva microbiomes of the two Pan species are more similar to one another, and the saliva microbiomes of the two human groups are more similar to one another, than are the saliva microbiomes of human workers and apes from the same sanctuary. We also looked for the existence of a core microbiome and find no evidence for a taxon-based core saliva microbiome for Homo or Pan. In addition, we studied the saliva microbiome from apes from the Leipzig Zoo, and found an extraordinary diversity in the zoo ape saliva microbiomes that is not found in the saliva microbiomes of the sanctuary animals. Conclusions The greater similarity of the saliva microbiomes of the two Pan species to one another, and of the two human groups to one another, are in accordance with both the phylogenetic relationships of the hosts as well as with host physiology. Moreover, the results from the zoo animals suggest that novel environments can have a large impact on the microbiome, and that microbiome analyses based on captive animals should be viewed with caution as they may not reflect the microbiome of animals in the wild. PMID:24025115

Whole genome sequencing revealed host adaptation-focused genomic plasticity of pathogenic Leptospira

PubMed Central

Xu, Yinghua; Zhu, Yongzhang; Wang, Yuezhu; Chang, Yung-Fu; Zhang, Ying; Jiang, Xiugao; Zhuang, Xuran; Zhu, Yongqiang; Zhang, Jinlong; Zeng, Lingbing; Yang, Minjun; Li, Shijun; Wang, Shengyue; Ye, Qiang; Xin, Xiaofang; Zhao, Guoping; Zheng, Huajun; Guo, Xiaokui; Wang, Junzhi

2016-01-01

Leptospirosis, caused by pathogenic Leptospira spp., has recently been recognized as an emerging infectious disease worldwide. Despite its severity and global importance, knowledge about the molecular pathogenesis and virulence evolution of Leptospira spp. remains limited. Here we sequenced and analyzed 102 isolates representing global sources. A high genomic variability were observed among different Leptospira species, which was attributed to massive gene gain and loss events allowing for adaptation to specific niche conditions and changing host environments. Horizontal gene transfer and gene duplication allowed the stepwise acquisition of virulence factors in pathogenic Leptospira evolved from a recent common ancestor. More importantly, the abundant expansion of specific virulence-related protein families, such as metalloproteases-associated paralogs, were exclusively identified in pathogenic species, reflecting the importance of these protein families in the pathogenesis of leptospirosis. Our observations also indicated that positive selection played a crucial role on this bacteria adaptation to hosts. These novel findings may lead to greater understanding of the global diversity and virulence evolution of Leptospira spp. PMID:26833181

Patterns of interactions of a large fish-parasite network in a tropical floodplain.

PubMed

Lima, Dilermando P; Giacomini, Henrique C; Takemoto, Ricardo M; Agostinho, Angelo A; Bini, Luis M

2012-07-01

1. Describing and explaining the structure of species interaction networks is of paramount importance for community ecology. Yet much has to be learned about the mechanisms responsible for major patterns, such as nestedness and modularity in different kinds of systems, of which large and diverse networks are a still underrepresented and scarcely studied fraction. 2. We assembled information on fishes and their parasites living in a large floodplain of key ecological importance for freshwater ecosystems in the Paraná River basin in South America. The resulting fish-parasite network containing 72 and 324 species of fishes and parasites, respectively, was analysed to investigate the patterns of nestedness and modularity as related to fish and parasite features. 3. Nestedness was found in the entire network and among endoparasites, multiple-host life cycle parasites and native hosts, but not in networks of ectoparasites, single-host life cycle parasites and non-native fishes. All networks were significantly modular. Taxonomy was the major host's attribute influencing both nestedness and modularity: more closely related host species tended to be associated with more nested parasite compositions and had greater chance of belonging to the same network module. Nevertheless, host abundance had a positive relationship with nestedness when only native host species pairs of the same network module were considered for analysis. 4. These results highlight the importance of evolutionary history of hosts in linking patterns of nestedness and formation of modules in the network. They also show that functional attributes of parasites (i.e. parasitism mode and life cycle) and origin of host populations (i.e. natives versus non-natives) are crucial to define the relative contribution of these two network properties and their dependence on other ecological factors (e.g. host abundance), with potential implications for community dynamics and stability. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

PubMed Central

Paczosa, Michelle K.

2016-01-01

SUMMARY Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore, K. pneumoniae strains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity in K. pneumoniae strains, and not every factor plays the same critical role in all virulent Klebsiella strains. Recent studies have identified additional K. pneumoniae virulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections. PMID:27307579

Select Host Restriction Factors Are Associated with HIV Persistence During Antiretroviral Therapy

PubMed Central

ABDEL-MOHSEN, Mohamed; WANG, Charlene; STRAIN, Matthew C.; LADA, Steven M.; DENG, Xutao; COCKERHAM, Leslie R.; PILCHER, Christopher D.; HECHT, Frederick M.; LIEGLER, Teri; RICHMAN, Douglas D.; DEEKS, Steven G.; PILLAI, Satish K.

2015-01-01

Objective The eradication of HIV necessitates elimination of the HIV latent reservoir. Identifying host determinants governing latency and reservoir size in the setting of antiretroviral therapy (ART) is an important step in developing strategies to cure HIV infection. We sought to determine the impact of cell-intrinsic immunity on the HIV latent reservoir. Design We investigated the relevance of a comprehensive panel of established anti-HIV-1 host restriction factors to multiple established virologic and immunologic measures of viral persistence in HIV-1-infected, ART-suppressed individuals. Methods We measured the mRNA expression of 42 anti-HIV-1 host restriction factors, levels of cell-associated HIV-1 RNA, levels of total pol and 2-LTR circle HIV-1 DNA, and immunophenotypes of CD4+ T cells in 72 HIV-1-infected subjects on suppressive ART (23 subjects initiated ART <1 year post-infection, and 49 subjects initiated ART >1 year post-infection). Correlations were analyzed using non-parametric tests. Results The enhanced expression of a few select host restriction factors, p21, schlafen 11, and PAF1, was strongly associated with reduced CD4+ T cell-associated HIV RNA during ART (p<0.001). In addition, our data suggested that ART perturbs the regulatory relationship between CD4+ T cell activation and restriction factor expression. Lastly, cell-intrinsic immune responses were significantly enhanced in subjects who initiated ART during early versus chronic infection, and may contribute to the reduced reservoir size observed in these individuals. Conclusions Intrinsic immune responses modulate HIV persistence during suppressive ART, and may be manipulated to enhance the efficacy of ART and promote viral eradication through reversal of latency in vivo. PMID:25602681

Regulation of Leishmania (L.) amazonensis Protein Expression by Host T Cell Dependent Responses: Differential Expression of Oligopeptidase B, Tryparedoxin Peroxidase and HSP70 Isoforms in Amastigotes Isolated from BALB/c and BALB/c Nude Mice

PubMed Central

Teixeira, Priscila Camillo; Velasquez, Leonardo Garcia; Lepique, Ana Paula; de Rezende, Eloiza; Bonatto, José Matheus Camargo; Barcinski, Marcello Andre; Cunha-Neto, Edecio; Stolf, Beatriz Simonsen

2015-01-01

Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania´s antigens. This work is the first to compare modifications in amastigotes’ proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression. PMID:25692783

Factors affecting variation in mortality of marine Atlantic salmon Salmo salar in Scotland.

PubMed

Soares, Silvia; Murray, Alexander G; Crumlish, Mags; Turnbull, James F; Green, Darren M

2013-03-26

Databases of site production have an important role to play in the investigation and understanding of diseases, since they store valuable amounts of disease and management data. Diseases pose an important constraint to economic expansion of aquaculture. They are dependent on the complex interacting factors of pathogen, environment, and host, and the causes of death can be related to nutritional, environmental, and genetic factors of the host or infectious agents. We examined the drivers of mortality from a single site-production database, which represented one-third of Scottish farmed salmon Salmo salar L. production in 2005, to determine whether mortality 'benchmarking' data could be generalised across sites and production cycles. We show that farm mortality records play an important role in studying mortality losses and identifying of management problems in production. We found that mortalities varied across the months of the year and with the time of year of initial stocking. Production cycles that started in the third quarter of the year had the highest mortality overall. Furthermore, we found site-to-site variation in mortality that may have been caused by either random occurrence of epidemics and environmental events or other local effects.

Contrasting determinants of abundance in ancestral and colonized ranges of an invasive brood parasite

USGS Publications Warehouse

Hahn, D.C.; O'Connor, R.J.; Scott, J. Michael; Heglund, Patricia J.; Morrison, Michael L.; Haufler, Jonathan B.; Wall, William A.

2002-01-01

Avian species distributions are typically regarded as constrained by spatially extensive variables such as climate, habitat, spatial patchiness, and microhabitat attributes. We hypothesized that the distribution of a brood parasite depends as strongly on host distribution patterns as on biophysical factors and examined this hypothesis with respect to the national distribution of the Brown-headed Cowbird (Molothrus ater). We applied a classification and regression (CART) analysis to data from the Breeding Bird Survey (BBS) and the Christmas Bird Count (CBC) and derived hierarchically organized statistical models of the influence of climate and weather, cropping and land use, and host abundance and distribution on the distribution of the Brown-headed Cowbird within the conterminous United States. The model accounted for 47.2% of the variation in cowbird incidence, and host abundance was the top predictor with an R2 of 18.9%. The other predictors identified by the model (crops 15.7%, weather and climate 14.3%, and region 9.6%) fit the ecological profile of this cowbird. We showed that host abundance was independent of these environmental predictors of cowbird distribution. At the regional scale host abundance played a very strong role in determining cowbird abundance in the cowbird?s colonized range east and west of their ancestral range in the Great Plains (26.6%). Crops were not a major predictor for cowbirds in their ancestral range, although they are the most important predictive factor (33%) for the grassland passerines that are the cowbird?s ancestral hosts. Consequently our findings suggest that the distribution of hosts does indeed take precedence over habitat attributes in shaping the cowbird?s distribution at a national scale, within an envelope of constraint set by biophysical factors.

Foot-and-Mouth Disease Virus Counteracts on Internal Ribosome Entry Site Suppression by G3BP1 and Inhibits G3BP1-Mediated Stress Granule Assembly via Post-Translational Mechanisms

PubMed Central

Ye, Xu; Pan, Ting; Wang, Dang; Fang, Liurong; Ma, Jun; Zhu, Xinyu; Shi, Yanling; Zhang, Keshan; Zheng, Haixue; Chen, Huanchun; Li, Kui; Xiao, Shaobo

2018-01-01

Foot-and-mouth disease (FMD) is a highly contagious, severe viral illness notifiable to the World Organization for Animal Health. The causative agent, FMD virus (FMDV), replicates rapidly and efficiently inhibits host translation and the innate immune response for it has developed multiple tactics to evade host defenses and takes over gene expression machinery in the host cell. Here, we report a systemic analysis of the proteome and phosphoproteome of FMDV-infected cells. Bioinformatics analysis suggested that FMDV infection shuts off host cap-dependent translation, but leaves intact internal ribosome entry site (IRES)-mediated translation for viral proteins. Interestingly, several FMDV IRES-transacting factors, including G3BP stress granule assembly factor 1 (G3BP1), were dephosphorylated during FMDV infection. Ectopic expression of G3BP1 inhibited FMDV IRES activity, promoted assembly of stress granules, and activated innate immune responses, collectively suppressing FMDV replication. To counteract these host protective responses, FMDV-induced dephosphorylation of G3BP1, compromising its inhibitory effect on viral IRES. In addition, FMDV also proteolytically cleaved G3BP1 by its 3C protease (3Cpro). G3BP1 was cleaved at glutamic acid-284 (E284) by FMDV 3Cpro, and this cleavage completely lost the abilities of G3BP1 to activate innate immunity and to inhibit FMDV replication. Together, these data provide new insights into the post-translational mechanisms by which FMDV limits host stress and antiviral responses and indicate that G3BP1 dephosphorylation and its proteolysis by viral protease are important factors in the failure of host defense against FMDV infection.

Host and Toxoplasma gondii genetic and non-genetic factors influencing the development of ocular toxoplasmosis: A systematic review.

PubMed

Fernández, Carolina; Jaimes, Jesús; Ortiz, María Camila; Ramírez, Juan David

2016-10-01

Toxoplasmosis is a cosmopolitan infection caused by the apicomplexan parasite Toxoplasma gondii. This infectious disease is widely distributed across the world where cats play an important role in its spread. The symptomatology caused by this parasite is diverse but the ocular affectation emerges as the most important clinical phenotype. Therefore, we conducted a systematic review of the current knowledge of ocular toxoplasmosis from the genetic diversity of the pathogen towards the treatment available for this infection. This review represents an update to the scientific community regarding the genetic diversity of the parasite, the genetic factors of the host, the molecular pathogenesis and its association with disease, the available diagnostic tools and the available treatment of patients undergoing ocular toxoplamosis. This review will be an update for the scientific community in order to encourage researchers to deploy cutting-edge investigation across this field.

Virus Infection and Death Receptor-Mediated Apoptosis.

PubMed

Zhou, Xingchen; Jiang, Wenbo; Liu, Zhongshun; Liu, Shuai; Liang, Xiaozhen

2017-10-27

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis.

Virus Infection and Death Receptor-Mediated Apoptosis

PubMed Central

Zhou, Xingchen; Jiang, Wenbo; Liu, Zhongshun; Liu, Shuai; Liang, Xiaozhen

2017-01-01

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis. PMID:29077026

Genome-Wide RNAi Screen Identifies Broadly-Acting Host Factors That Inhibit Arbovirus Infection

PubMed Central

Yasunaga, Ari; Hanna, Sheri L.; Li, Jianqing; Cho, Hyelim; Rose, Patrick P.; Spiridigliozzi, Anna; Gold, Beth; Diamond, Michael S.; Cherry, Sara

2014-01-01

Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi) pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV), a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts. PMID:24550726

Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens

PubMed Central

Kers, Jannigje G.; Velkers, Francisca C.; Fischer, Egil A. J.; Hermes, Gerben D. A.; Stegeman, J. A.; Smidt, Hauke

2018-01-01

The initial development of intestinal microbiota in poultry plays an important role in production performance, overall health and resistance against microbial infections. Multiplexed sequencing of 16S ribosomal RNA gene amplicons is often used in studies, such as feed intervention or antimicrobial drug trials, to determine corresponding effects on the composition of intestinal microbiota. However, considerable variation of intestinal microbiota composition has been observed both within and across studies. Such variation may in part be attributed to technical factors, such as sampling procedures, sample storage, DNA extraction, the choice of PCR primers and corresponding region to be sequenced, and the sequencing platforms used. Furthermore, part of this variation in microbiota composition may also be explained by different host characteristics and environmental factors. To facilitate the improvement of design, reproducibility and interpretation of poultry microbiota studies, we have reviewed the literature on confounding factors influencing the observed intestinal microbiota in chickens. First, it has been identified that host-related factors, such as age, sex, and breed, have a large effect on intestinal microbiota. The diversity of chicken intestinal microbiota tends to increase most during the first weeks of life, and corresponding colonization patterns seem to differ between layer- and meat-type chickens. Second, it has been found that environmental factors, such as biosecurity level, housing, litter, feed access and climate also have an effect on the composition of the intestinal microbiota. As microbiota studies have to deal with many of these unknown or hidden host and environmental variables, the choice of study designs can have a great impact on study outcomes and interpretation of the data. Providing details on a broad range of host and environmental factors in articles and sequence data repositories is highly recommended. This creates opportunities to combine data from different studies for meta-analysis, which will facilitate scientific breakthroughs toward nutritional and husbandry associated strategies to improve animal health and performance. PMID:29503637

Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens.

PubMed

Kers, Jannigje G; Velkers, Francisca C; Fischer, Egil A J; Hermes, Gerben D A; Stegeman, J A; Smidt, Hauke

2018-01-01

The initial development of intestinal microbiota in poultry plays an important role in production performance, overall health and resistance against microbial infections. Multiplexed sequencing of 16S ribosomal RNA gene amplicons is often used in studies, such as feed intervention or antimicrobial drug trials, to determine corresponding effects on the composition of intestinal microbiota. However, considerable variation of intestinal microbiota composition has been observed both within and across studies. Such variation may in part be attributed to technical factors, such as sampling procedures, sample storage, DNA extraction, the choice of PCR primers and corresponding region to be sequenced, and the sequencing platforms used. Furthermore, part of this variation in microbiota composition may also be explained by different host characteristics and environmental factors. To facilitate the improvement of design, reproducibility and interpretation of poultry microbiota studies, we have reviewed the literature on confounding factors influencing the observed intestinal microbiota in chickens. First, it has been identified that host-related factors, such as age, sex, and breed, have a large effect on intestinal microbiota. The diversity of chicken intestinal microbiota tends to increase most during the first weeks of life, and corresponding colonization patterns seem to differ between layer- and meat-type chickens. Second, it has been found that environmental factors, such as biosecurity level, housing, litter, feed access and climate also have an effect on the composition of the intestinal microbiota. As microbiota studies have to deal with many of these unknown or hidden host and environmental variables, the choice of study designs can have a great impact on study outcomes and interpretation of the data. Providing details on a broad range of host and environmental factors in articles and sequence data repositories is highly recommended. This creates opportunities to combine data from different studies for meta-analysis, which will facilitate scientific breakthroughs toward nutritional and husbandry associated strategies to improve animal health and performance.

Basic immunology of antibody targeted radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Jeffrey Y.C.

2006-10-01

Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy.

Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens

PubMed Central

Chasman, Deborah; Walters, Kevin B.; Lopes, Tiago J. S.; Eisfeld, Amie J.; Kawaoka, Yoshihiro; Roy, Sushmita

2016-01-01

Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection. PMID:27403523

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gagne, Roderick B.; Hogan, J. Derek; McIntyre, Peter B.

1. Co-introductions of non-native parasites with non-native hosts can be a major driver of disease emergence in native species, but the conditions that promote the establishment and spread of nonnative parasites remain poorly understood. Here, we characterise the infection of a native host species by a non-native parasite relative to the distribution and density of the original non-native host species and a suite of organismal and environmental factors that have been associated with parasitism, but not commonly considered within a single system. 2. We examined the native Hawaiian goby Awaous stamineus across 23 catchments on five islands for infection bymore » the non-native nematode parasite Camallanus cotti. We used model selection to test whether parasite infection was associated with the genetic diversity, size and population density of native hosts, the distribution and density of non-native hosts, land use and water quality. 3. We found that the distribution of non-native C. cotti parasites has become decoupled from the non-native hosts that were primary vectors of introduction to the Hawaiian Islands. Although no single intrinsic or extrinsic factor was identified that best explains parasitism of A. stamineus by C. cotti, native host size, population density and water quality were consistently identified as influencing parasite intensity and prevalence. 4. The introduction of non-native species can indirectly influence native species through infection of co-introduced parasites. Here, we show that the effects of enemy addition can extend beyond the range of non-native hosts through the independent spread of non-native parasites. This suggests that control of non-native hosts is not sufficient to halt the spread of introduced parasites. Furthermore, designing importation regulations to prevent host parasite co-introductions can promote native species conservation, even in remote areas that may not seem susceptible to human influence.« less

Natal Host Plants Can Alter Herbivore Competition.

PubMed

Pan, Huipeng; Preisser, Evan L; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun; Zhang, Youjun

2016-01-01

Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore's natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems.

Health assessment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect of haematophagous parasites on haematological parameters.

PubMed

Marcus, Alan D; Higgins, Damien P; Gray, Rachael

2015-06-01

Evaluation of the health status of free-ranging populations is important for understanding the impact of disease on individuals and on population demography and viability. In this study, haematological reference intervals were developed for free-ranging endangered Australian sea lion (Neophoca cinerea) pups within the context of endemic hookworm (Uncinaria sanguinis) infection and the effects of pathogen, host, and environment factors on the variability of haematological parameters were investigated. Uncinaria sanguinis was identified as an important agent of disease, with infection causing regenerative anaemia, hypoproteinaemia, and a predominantly lymphocytic-eosinophilic systemic inflammatory response. Conversely, the effects of sucking lice (Antarctophthirus microchir) were less apparent and infestation in pups appears unlikely to cause clinical impact. Overall, the effects of U. sanguinis, A. microchir, host factors (standard length, body condition, pup sex, moult status, and presence of lesions), and environment factors (capture-type and year of sampling) accounted for 26-65% of the total variance observed in haematological parameters. Importantly, this study demonstrated that anaemia in neonatal Australian sea lion pups is not solely a benign physiological response to host-environment changes, but largely reflects a significant pathological process. This impact of hookworm infection on pup health has potential implications for the development of foraging and diving behaviour, which would subsequently influence the independent survival of juveniles following weaning. The haematological reference intervals developed in this study can facilitate long-term health surveillance, which is critical for the early recognition of changes in disease impact and to inform conservation management. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterizing the avian gut microbiota: membership, driving influences, and potential function.

PubMed

Waite, David W; Taylor, Michael W

2014-01-01

Birds represent a diverse and evolutionarily successful lineage, occupying a wide range of niches throughout the world. Like all vertebrates, avians harbor diverse communities of microorganisms within their guts, which collectively fulfill important roles in providing the host with nutrition and protection from pathogens. Although many studies have investigated the role of particular microbes in the guts of avian species, there has been no attempt to unify the results of previous, sequence-based studies to examine the factors that shape the avian gut microbiota as a whole. In this study, we present the first meta-analysis of the avian gut microbiota, using 16S rRNA gene sequences obtained from a range of publicly available clone-library and amplicon pyrosequencing data. We investigate community membership and structure, as well as probe the roles of some of the key biological factors that influence the gut microbiota of other vertebrates, such as host phylogeny, location within the gut, diet, and association with humans. Our results indicate that, across avian studies, the microbiota demonstrates a similar phylum-level composition to that of mammals. Host bird species is the most important factor in determining community composition, although sampling site, diet, and captivity status also contribute. These analyses provide a first integrated look at the composition of the avian microbiota, and serve as a foundation for future studies in this area.

Bluetongue virus spread in Europe is a consequence of climatic, landscape and vertebrate host factors as revealed by phylogeographic inference

PubMed Central

Palmarini, Massimo; Mertens, Peter

2017-01-01

Spatio-temporal patterns of the spread of infectious diseases are commonly driven by environmental and ecological factors. This is particularly true for vector-borne diseases because vector populations can be strongly affected by host distribution as well as by climatic and landscape variables. Here, we aim to identify environmental drivers for bluetongue virus (BTV), the causative agent of a major vector-borne disease of ruminants that has emerged multiple times in Europe in recent decades. In order to determine the importance of climatic, landscape and host-related factors affecting BTV diffusion across Europe, we fitted different phylogeographic models to a dataset of 113 time-stamped and geo-referenced BTV genomes, representing multiple strains and serotypes. Diffusion models using continuous space revealed that terrestrial habitat below 300 m altitude, wind direction and higher livestock densities were associated with faster BTV movement. Results of discrete phylogeographic analysis involving generalized linear models broadly supported these findings, but varied considerably with the level of spatial partitioning. Contrary to common perception, we found no evidence for average temperature having a positive effect on BTV diffusion, though both methodological and biological reasons could be responsible for this result. Our study provides important insights into the drivers of BTV transmission at the landscape scale that could inform predictive models of viral spread and have implications for designing control strategies. PMID:29021180

Characterizing the avian gut microbiota: membership, driving influences, and potential function

PubMed Central

Waite, David W.; Taylor, Michael W.

2014-01-01

Birds represent a diverse and evolutionarily successful lineage, occupying a wide range of niches throughout the world. Like all vertebrates, avians harbor diverse communities of microorganisms within their guts, which collectively fulfill important roles in providing the host with nutrition and protection from pathogens. Although many studies have investigated the role of particular microbes in the guts of avian species, there has been no attempt to unify the results of previous, sequence-based studies to examine the factors that shape the avian gut microbiota as a whole. In this study, we present the first meta-analysis of the avian gut microbiota, using 16S rRNA gene sequences obtained from a range of publicly available clone-library and amplicon pyrosequencing data. We investigate community membership and structure, as well as probe the roles of some of the key biological factors that influence the gut microbiota of other vertebrates, such as host phylogeny, location within the gut, diet, and association with humans. Our results indicate that, across avian studies, the microbiota demonstrates a similar phylum-level composition to that of mammals. Host bird species is the most important factor in determining community composition, although sampling site, diet, and captivity status also contribute. These analyses provide a first integrated look at the composition of the avian microbiota, and serve as a foundation for future studies in this area. PMID:24904538

Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2017-01-01

Recurrent urinary tract infection (UTI) might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market.

Interferon in lyssavirus infection.

PubMed

Rieder, Martina; Finke, Stefan; Conzelmann, Karl-Klaus

2012-01-01

Rabies is a zoonosis still claiming more than 50 000 human deaths per year. Typically, human cases are due to infection with rabies virus, the prototype of the Lyssavirus genus, but sporadic cases of rabies-like encephalitis caused by other lyssaviruses have been reported. In contrast to rabies virus, which has an extremely broad host range including many terrestrial warm-blooded animals, rabies-related viruses are associated predominantly with bats and rarely infect terrestrial species. In spite of a very close genetic relationship of rabies and rabies-related viruses, the factors determining the limited host range of rabies-related viruses are not clear. In the past years the importance of viral countermeasures against the host type I interferon system for establishment of an infection became evident. The rabies virus phosphoprotein (P) has emerged as a critical factor required for paralysing the signalling cascades leading to transcriptional activation of interferon genes as well as interferon signalling pathways, thereby limiting expression of antiviral and immune stimulatory genes. Comparative studies would be of interest in order to determine whether differential abilities of the lyssavirus P proteins contribute to the restricted host range of lyssaviruses.

Leishmania exosomes and other virulence factors: Impact on innate immune response and macrophage functions.

PubMed

Atayde, Vanessa Diniz; Hassani, Kasra; da Silva Lira Filho, Alonso; Borges, Andrezza Raposo; Adhikari, Anupam; Martel, Caroline; Olivier, Martin

2016-11-01

Leishmania parasites are the causative agents of the leishmaniases, a collection of vector-borne diseases that range from simple cutaneous to fatal visceral forms. Employing potent immune modulation mechanisms, Leishmania is able to render the host macrophage inactive and persist inside its phagolysosome. In the last few years, the role of exosomes in Leishmania-host interactions has been increasingly investigated. For instance, it was reported that Leishmania exosome release is augmented following temperature shift, a condition mimicking parasite's entry into its mammalian host. Leishmania exosomes were found to strongly affect macrophage cell signaling and functions, similarly to whole parasites. Importantly, these vesicles were shown to be pro-inflammatory, capable to recruit neutrophils at their inoculation site exacerbating the pathology. In this review, we provide the most recent insights on the role of exosomes and other virulence factors, especially the surface protease GP63, in Leishmania-host interactions, deepening our knowledge on leishmaniasis and paving the way for the development of new therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

Towards a better understanding of Lactobacillus rhamnosus GG - host interactions

PubMed Central

2014-01-01

Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains. PMID:25186587

Fungal Strategies to Evade the Host Immune Recognition.

PubMed

Hernández-Chávez, Marco J; Pérez-García, Luis A; Niño-Vega, Gustavo A; Mora-Montes, Héctor M

2017-09-23

The recognition of fungal cells by the host immune system is key during the establishment of a protective anti-fungal response. Even though the immune system has evolved a vast number of processes to control these organisms, they have developed strategies to fight back, avoiding the proper recognition by immune components and thus interfering with the host protective mechanisms. Therefore, the strategies to evade the immune system are as important as the virulence factors and attributes that damage the host tissues and cells. Here, we performed a thorough revision of the main fungal tactics to escape from the host immunosurveillance processes. These include the composition and organization of the cell wall, the fungal capsule, the formation of titan cells, biofilms, and asteroid bodies; the ability to undergo dimorphism; and the escape from nutritional immunity, extracellular traps, phagocytosis, and the action of humoral immune effectors.

The role of infectious disease in marine communities: chapter 5

USGS Publications Warehouse

Lafferty, Kevin D.; Harvell, C. Drew

2014-01-01

Marine ecologists recognize that infectious diseases play and important role in ocean ecosystems. This role may have increased in some host taxa over time (Ward and Lafferty 2004). We begin this chapter by introducing infectious agents and their relationships with their hosts in marine systems. We then put infectious disease agents with their hosts in marine systems. We then put infectious disease agents in the perspective of marine biodiversity and discuss the various factors that affect parasites. Specifically, we introduce some basin epidemiological concepts, including the effects of stress and free-living diversity on parasites. Following this, we give brief consideration to communities of parasites within their hosts, particularly as these can lead to general insights into community ecology. We also give examples of how infectious diseases affect host populations, scaling up to marine communities. Finally, we present examples of marine infectious disease that impair conservation and fisheries.

Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

PubMed

Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

2007-07-27

Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

Multiple Vibrio fischeri genes are involved in biofilm formation and host colonization

PubMed Central

Chavez-Dozal, Alba; Hogan, David; Gorman, Clayton; Quintanal-Villalonga, Alvaro; Nishiguchi, Michele K.

2012-01-01

Biofilms are increasingly recognized as the predominant form for survival in the environment for most bacteria. The successful colonization of Vibrio fischeri in its squid host Euprymna tasmanica, involves complex microbe-host interactions mediated by specific genes that are essential for biofilm formation and colonization. In the present investigation, structural and regulatory genes were selected to study their role in biofilm formation and host colonization. We have mutated several genes (pilT, pilU, flgF, motY, ibpA and mifB) by an insertional inactivation strategy. Results demonstrate that structural genes responsible for synthesis of type IV pili and flagella are crucial for biofilm formation and host infection. Moreover, regulatory genes affect colony aggregation by various mechanisms including alteration of synthesis of transcriptional factors and regulation of extracellular polysaccharide production. These results reflect the significance of how genetic alterations influence communal behavior, which is important in understanding symbiotic relationships. PMID:22486781

Pathogenic adaptations to host-derived antibacterial copper

PubMed Central

Chaturvedi, Kaveri S.; Henderson, Jeffrey P.

2014-01-01

Recent findings suggest that both host and pathogen manipulate copper content in infected host niches during infections. In this review, we summarize recent developments that implicate copper resistance as an important determinant of bacterial fitness at the host-pathogen interface. An essential mammalian nutrient, copper cycles between copper (I) (Cu+) in its reduced form and copper (II) (Cu2+) in its oxidized form under physiologic conditions. Cu+ is significantly more bactericidal than Cu2+ due to its ability to freely penetrate bacterial membranes and inactivate intracellular iron-sulfur clusters. Copper ions can also catalyze reactive oxygen species (ROS) generation, which may further contribute to their toxicity. Transporters, chaperones, redox proteins, receptors and transcription factors and even siderophores affect copper accumulation and distribution in both pathogenic microbes and their human hosts. This review will briefly cover evidence for copper as a mammalian antibacterial effector, the possible reasons for this toxicity, and pathogenic resistance mechanisms directed against it. PMID:24551598

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System.

PubMed

Lunney, Joan K; Fang, Ying; Ladinig, Andrea; Chen, Nanhua; Li, Yanhua; Rowland, Bob; Renukaradhya, Gourapura J

2016-01-01

This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis, and control. Worldwide, PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic mechanisms, and host immunity, with a special focus on immune factors that modulate PRRSV infections during the acute and chronic/persistent disease phases. We address genetic control of host resistance and probe effects of PRRSV infection on reproductive traits. A major goal is to identify cellular/viral targets and pathways for designing more effective vaccines and therapeutics. Based on progress in viral reverse genetics, host transcriptomics and genomics, and vaccinology and adjuvant technologies, we have identified new areas for PRRS control and prevention. Finally, we highlight the gaps in our knowledge base and the need for advanced molecular and immune tools to stimulate PRRS research and field applications.

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

PubMed Central

Chibucos, Marcus C.; Soliman, Sameh; Gebremariam, Teclegiorgis; Lee, Hongkyu; Daugherty, Sean; Orvis, Joshua; Shetty, Amol C.; Crabtree, Jonathan; Hazen, Tracy H.; Etienne, Kizee A.; Kumari, Priti; O'Connor, Timothy D.; Rasko, David A.; Filler, Scott G.; Fraser, Claire M.; Lockhart, Shawn R.; Skory, Christopher D.; Ibrahim, Ashraf S.; Bruno, Vincent M.

2016-01-01

Mucormycosis is a life-threatening infection caused by Mucorales fungi. Here we sequence 30 fungal genomes, and perform transcriptomics with three representative Rhizopus and Mucor strains and with human airway epithelial cells during fungal invasion, to reveal key host and fungal determinants contributing to pathogenesis. Analysis of the host transcriptional response to Mucorales reveals platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells. The unique presence of CotH invasins in all invasive Mucorales, and the correlation between CotH gene copy number and clinical prevalence, are consistent with an important role for these proteins in mucormycosis pathogenesis. Our work provides insight into the evolution of this medically and economically important group of fungi, and identifies several molecular pathways that might be exploited as potential therapeutic targets. PMID:27447865

Shedding of tumor necrosis factor receptor 1 induced by protein A decreases tumor necrosis factor alpha availability and inflammation during systemic Staphylococcus aureus infection.

PubMed

Giai, Constanza; Gonzalez, Cintia; Ledo, Camila; Garofalo, Ailin; Di Genaro, María Silvia; Sordelli, Daniel O; Gomez, Marisa I

2013-11-01

Staphylococcus aureus infections are an important public health concern due to their increasing incidence and high rates of mortality. The success of S. aureus as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of tumor necrosis factor alpha (TNF-α) in the initial host defense against systemic staphylococcal infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-α receptor 1 (TNFR1). In this study, we demonstrate that S. aureus, via protein A-mediated signaling, induces early shedding of TNFR1, which precedes the secretion of TNF-α in vitro and in vivo. The results obtained using a protein A-deficient mutant and tnfr1(-/-) mice strongly suggest that the increased levels of soluble TNFR1 present during experimental S. aureus infection may neutralize circulating TNF-α and impair the host inflammatory response. Early shedding of TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response.

Human Meningitis-Associated Escherichia coli.

PubMed

Kim, Kwang Sik

2016-05-01

Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essential step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis.

Human Meningitis-Associated Escherichia coli

PubMed Central

KIM, KWANG SIK

2016-01-01

E. coli is the most common Gram-negative bacillary organism causing meningitis and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Our incomplete knowledge of its pathogenesis contributes to such mortality and morbidity. Recent reports of E. coli strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. Studies using in vitro and in vivo models of the blood-brain barrier have shown that E. coli meningitis follows a high-degree of bacteremia and invasion of the blood-brain barrier. E. coli invasion of the blood-brain barrier, the essentials step in the development of E. coli meningitis, requires specific microbial and host factors as well as microbe- and host-specific signaling molecules. Blockade of such microbial and host factors contributing to E. coli invasion of the blood-brain barrier is shown to be efficient in preventing E. coli penetration into the brain. The basis for requiring a high-degree of bacteremia for E. coli penetration of the blood-brain barrier, however, remains unclear. Continued investigation on the microbial and host factors contributing to a high-degree of bacteremia and E. coli invasion of the blood-brain barrier is likely to identify new targets for prevention and therapy of E. coli meningitis. PMID:27223820

Virulence factor rtx in Legionella pneumophila, evidence suggesting it is a modular multifunctional protein.

PubMed

D'Auria, Giuseppe; Jiménez, Núria; Peris-Bondia, Francesc; Pelaz, Carmen; Latorre, Amparo; Moya, Andrés

2008-01-14

The repeats in toxin (Rtx) are an important pathogenicity factor involved in host cells invasion of Legionella pneumophila and other pathogenic bacteria. Its role in escaping the host immune system and cytotoxic activity is well known. Its repeated motives and modularity make Rtx a multifunctional factor in pathogenicity. The comparative analysis of rtx gene among 6 strains of L. pneumophila showed modularity in their structures. Among compared genomes, the N-terminal region of the protein presents highly dissimilar repeats with functionally similar domains. On the contrary, the C-terminal region is maintained with a fashionable modular configuration, which gives support to its proposed role in adhesion and pore formation. Despite the variability of rtx among the considered strains, the flanking genes are maintained in synteny and similarity. In contrast to the extracellular bacteria Vibrio cholerae, in which the rtx gene is highly conserved and flanking genes have lost synteny and similarity, the gene region coding for the Rtx toxin in the intracellular pathogen L. pneumophila shows a rapid evolution. Changes in the rtx could play a role in pathogenicity. The interplay of the Rtx toxin with host membranes might lead to the evolution of new variants that are able to escape host cell defences.

Pathogenesis and host defence against Mucorales: the role of cytokines and interaction with antifungal drugs.

PubMed

Roilides, Emmanuel; Antachopoulos, Charalampos; Simitsopoulou, Maria

2014-12-01

Innate immune response, including macrophages, neutrophils and dendritic cells and their respective receptors, plays an important role in host defences against Mucorales with differential activity against specific fungal species, while adaptive immunity is not the first line of defence. A number of endogenous and exogenous factors, such as cytokines and growth factors as well as certain antifungal agents have been found that they influence innate immune response to these organisms. Used alone or especially in combination have been shown to exert antifungal effects against Mucorales species. These findings suggest novel ways of adjunctive therapy for patients with invasive mucormycosis. © 2014 Blackwell Verlag GmbH.

Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

PubMed Central

Sistrunk, Jeticia R.; Nickerson, Kourtney P.; Chanin, Rachael B.; Rasko, David A.

2016-01-01

SUMMARY Bacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to this in vivo signal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens. PMID:27464994

The Many Facets of Lipooligosaccharide as a Virulence Factor for Histophilus somni.

PubMed

Inzana, Thomas J

2016-01-01

The lipooligosaccharide (LOS) of Histophilus somni is a multifaceted molecule that provides critical protection to the bacterium against host defenses, may act as an adhesin, and like similar molecules of gram-negative bacteria, is an endotoxin that signals through toll-like receptor 4 and NF-κB to cause inflammation. The lipid A component is responsible for the endotoxic and apoptotic activity of the LOS. The H. somni LOS lacks O-side chains typically characteristic of gram-negative bacteria that have lipopolysaccharide, but has a complex, microheterogeneous outer core. The LOS of disease isolates is capable of undergoing structural and antigenic phase variation of its outer core due to slip-strand mispairing of glycosyltransferase genes that contain repetitive sequences of DNA base pairs. Such variation enables the bacteria to evade bactericidal antibodies made to oligosaccharide antigens. In addition, the LOS can be decorated with phase-variable phosphorylcholine (ChoP), which binds to platelet-activating factor receptor on host cells, thereby aiding in colonization of the upper respiratory tract. However, ChoP is likely not expressed when the bacteria are in systemic sites because ChoP also binds to C-reactive protein, resulting in activation of host complement and promoting bactericidal activity. The structure of some LOS outer core chains is identical to oligosaccharides on host glycosphingolipids of red blood cells, other cells, and merconium (lacto-N-neotetraose, lacto-N-biose, N-acetyllactosamine, etc.). Furthermore, terminal galactose residues on LOS and elsewhere are decorated with sialic acid, which blocks antibody binding, activation of complement, phagocytosis, and intracellular killing. Therefore, antigenic mimicry of host antigens is an important defense mechanism provided by the oligosaccharide component of the LOS to avoid innate and adaptive host defense mechanisms. However, some strains of H. somni isolated from the bovine genital tract, particularly the normal bovine prepuce, are incapable of LOS phase variation, sialylation of the LOS, and expression of ChoP. At least 1 such strain has been shown to be avirulent, underscoring the importance of the LOS as a virulence factor, although this strain is deficient in other factors as well. The structure and arrangement of the inner core glycoses (heptose and 3-deoxy-D-manno-2-octulosnic acid) is remarkably similar to the inner core oligosaccharide on some strains of Neisseria spp., and mutants that contain a truncated LOS oligosaccharide are considerably more serum-sensitive than the parent strain. Therefore, the LOS is a critical component that enables H. somni to resist host defenses and cause disease.

Global genomics and proteomics approaches to identify host factors as targets to induce resistance against Tomato bushy stunt virus.

PubMed

Nagy, Peter D; Pogany, Judit

2010-01-01

The success of RNA viruses as pathogens of plants, animals, and humans depends on their ability to reprogram the host cell metabolism to support the viral infection cycle and to suppress host defense mechanisms. Plus-strand (+)RNA viruses have limited coding potential necessitating that they co-opt an unknown number of host factors to facilitate their replication in host cells. Global genomics and proteomics approaches performed with Tomato bushy stunt virus (TBSV) and yeast (Saccharomyces cerevisiae) as a model host have led to the identification of 250 host factors affecting TBSV RNA replication and recombination or bound to the viral replicase, replication proteins, or the viral RNA. The roles of a dozen host factors involved in various steps of the replication process have been validated in yeast as well as a plant host. Altogether, the large number of host factors identified and the great variety of cellular functions performed by these factors indicate the existence of a truly complex interaction between TBSV and the host cell. This review summarizes the advantages of using a simple plant virus and yeast as a model host to advance our understanding of virus-host interactions at the molecular and cellular levels. The knowledge of host factors gained can potentially be used to inhibit virus replication via gene silencing, expression of dominant negative mutants, or design of specific chemical inhibitors leading to novel specific or broad-range resistance and antiviral tools against (+)RNA plant viruses. Copyright © 2010 Elsevier Inc. All rights reserved.

Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense.

PubMed

Wiemann, Philipp; Perevitsky, Adi; Lim, Fang Yun; Shadkchan, Yana; Knox, Benjamin P; Landero Figueora, Julio A; Choera, Tsokyi; Niu, Mengyao; Steinberger, Andrew J; Wüthrich, Marcel; Idol, Rachel A; Klein, Bruce S; Dinauer, Mary C; Huttenlocher, Anna; Osherov, Nir; Keller, Nancy P

2017-05-02

The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI) mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs), and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically) or enhancement of copper-exporting activity (CrpA) in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Echinostoma trivolvis (Digenea: Echinostomatidae) second intermediate host preference matches host suitability.

PubMed

Wojdak, Jeremy M; Clay, Letitia; Moore, Sadé; Williams, Taylore; Belden, Lisa K

2013-02-01

Many trematodes infect a single mollusk species as their first intermediate host, and then infect a variety of second intermediate host species. Determining the factors that shape host specificity is an important step towards understanding trematode infection dynamics. Toward this end, we studied two pond snails (Physa gyrina and Helisoma trivolvis) that can be infected as second intermediate hosts by the trematode Echinostoma trivolvis lineage a (ETa). We performed laboratory preference trials with ETa cercariae in the presence of both snail species and also characterized host suitability by quantifying encystment and excystment success for each host species alone. We tested the prediction that trematodes might preferentially infect species other than their obligate first intermediate host (in this case, H. trivolvis) as second intermediate hosts to avoid potentially greater host mortality associated with residing in first intermediate hosts. In our experiments, ETa had roughly equivalent encystment success in Helisoma and Physa snails, but greater excystment success in Physa, when offered each species in isolation. Also, the presence of the symbiotic oligochaete Chaetogaster limnaei in a subset of Helisoma snails reduced encystment success in those individuals. When both hosts were present, we found dramatically reduced infection prevalence and intensity in Helisoma-ETa cercariae strongly preferred Physa. Thus, the presence of either an alternative host, or a predator of free-living parasites, offered protection for Helisoma snails from E. trivolvis lineage a infection.

Yersinia adhesin A (YadA)--beauty & beast.

PubMed

Mühlenkamp, Melanie; Oberhettinger, Philipp; Leo, Jack C; Linke, Dirk; Schütz, Monika S

2015-02-01

The trimeric autotransporter adhesin Yersinia adhesin A is the prototype of the type Vc secretion systems. It is expressed by enteropathogenic Yersinia enterocolitica and Yersinia pseudotuberculosis strains, but not by Yersinia pestis. A characteristic trait of YadA is its modular composition and trimeric nature. YadA consists of an N-terminal passenger domain which is exposed on the bacterial cell surface. The translocation of this passenger onto the surface is facilitated by a C-terminal β-barrel domain which concomitantly anchors YadA into the outer membrane with three YadA monomers contributing to the formation of a single β-barrel. In Y. enterocolitica, but not Y. pseudotuberculosis, YadA is a decisive virulence factor and its deletion renders the bacteria virtually avirulent in mouse models of infection. This striking importance of YadA in infection may derive from its manifold functions in host cell interaction. Presumably the most important function of YadA is that it mediates adhesion to extracellular matrix components of eukaryotic host cells. Only tight adhesion allows for the injection of "anti-host" effector proteins via a type III secretion system into the host cell cytosol. These effector proteins enable Yersinia to subvert the host immune system in order to replicate and establish infection. YadA is also essential for the survival of Y. enterocolitica upon contact with serum, an important immune-evasion mechanism called serum resistance. To this end, YadA interacts with several components of the host complement system, the first line of immune defense. This review will summarize recent findings about the structure and biogenesis of YadA and its interactions with the host complement system. Copyright © 2015 Elsevier GmbH. All rights reserved.

Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature

PubMed Central

Gerasimidis, Konstantinos; Edwards, Christine Ann; Shaikh, M. Guftar

2016-01-01

The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis. PMID:27703805

Host and geographic structure of endophytic and endolichenic fungi at a continental scale.

PubMed

U'Ren, Jana M; Lutzoni, François; Miadlikowska, Jolanta; Laetsch, Alexander D; Arnold, A Elizabeth

2012-05-01

Endophytic and endolichenic fungi occur in healthy tissues of plants and lichens, respectively, playing potentially important roles in the ecology and evolution of their hosts. However, previous sampling has not comprehensively evaluated the biotic, biogeographic, and abiotic factors that structure their communities. Using molecular data we examined the diversity, composition, and distributions of 4154 endophytic and endolichenic Ascomycota cultured from replicate surveys of ca. 20 plant and lichen species in each of five North American sites (Madrean coniferous forest, Arizona; montane semideciduous forest, North Carolina; scrub forest, Florida; Beringian tundra and forest, western Alaska; subalpine tundra, eastern central Alaska). Endolichenic fungi were more abundant and diverse per host species than endophytes, but communities of endophytes were more diverse overall, reflecting high diversity in mosses and lycophytes. Endophytes of vascular plants were largely distinct from fungal communities that inhabit mosses and lichens. Fungi from closely related hosts from different regions were similar in higher taxonomy, but differed at shallow taxonomic levels. These differences reflected climate factors more strongly than geographic distance alone. Our study provides a first evaluation of endophytic and endolichenic fungal associations with their hosts at a continental scale. Both plants and lichens harbor abundant and diverse fungal communities whose incidence, diversity, and composition reflect the interplay of climatic patterns, geographic separation, host type, and host lineage. Although culture-free methods will inform future work, our study sets the stage for empirical assessments of ecological specificity, metabolic capability, and comparative genomics.

Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production To Promote Tissue Engineered Periosteum-Mediated Allograft Healing

PubMed Central

Hoffman, Michael D.

2015-01-01

Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogeneous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration. PMID:25818449

Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition.

PubMed

Ellington, Sascha R; King, Caroline C; Kourtis, Athena P

2011-01-01

Mother-to-child transmission (MTCT) is the most important mode of HIV-1 acquisition among infants and children and it can occur in utero , intrapartum and postnatally through breastfeeding. Great progress has been made in preventing MTCT through use of antiretroviral regimens during gestation, labor/delivery and breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain incompletely understood. This review focuses on select host factors affecting MTCT, in particular genetic factors, coexisting infections, behavioral factors and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1 viral load, an important determinant of MTCT, through use of antiretroviral agents, complementary focus on overall maternal health is often neglected. By addressing coinfections in mothers and infants, improving the mother's nutritional status and modifying risky behaviors and practices, not only is maternal and child health improved, but a direct benefit in reducing MTCT can be derived. The study of genetic variations in susceptibility to HIV-1 infection is rapidly evolving, and the future is likely to bring revolutionary changes in HIV-1 prevention by enhancing natural resistance to infection and by individually tailoring pharmacologic regimens.

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition

PubMed Central

Ellington, Sascha R; King, Caroline C; Kourtis, Athena P

2017-01-01

Mother-to-child transmission (MTCT) is the most important mode of HIV-1 acquisition among infants and children and it can occur in utero, intrapartum and postnatally through breastfeeding. Great progress has been made in preventing MTCT through use of antiretroviral regimens during gestation, labor/delivery and breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain incompletely understood. This review focuses on select host factors affecting MTCT, in particular genetic factors, coexisting infections, behavioral factors and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1 viral load, an important determinant of MTCT, through use of antiretroviral agents, complementary focus on overall maternal health is often neglected. By addressing coinfections in mothers and infants, improving the mother’s nutritional status and modifying risky behaviors and practices, not only is maternal and child health improved, but a direct benefit in reducing MTCT can be derived. The study of genetic variations in susceptibility to HIV-1 infection is rapidly evolving, and the future is likely to bring revolutionary changes in HIV-1 prevention by enhancing natural resistance to infection and by individually tailoring pharmacologic regimens. PMID:29348780

Contrasting amino acid profiles among permissive and non-permissive hosts of Candidatus Liberibacter asiaticus, putative causal agent of Huanglongbing

PubMed Central

Alabi, Olufemi J.; Simpson, Catherine R.; Jifon, John L.

2017-01-01

Huanglongbing is a devastating disease of citrus. In this study, a comprehensive profile of phloem sap amino acids (AA) in four permissive host plants of Candidatus Liberibacter asiaticus (CLas) and three non-permissive Rutaceae plants was conducted to gain a better understanding of host factors that may promote or suppress the bacterium. The AA profiles of Diaphorina citri nymphs and adults were similarly analyzed. A total of 38 unique AAs were detected in phloem sap of the various plants and D. citri samples, with phloem sap of young shoots containing more AAs and at higher concentrations than their mature counterparts. All AAs detected in phloem sap of non-permissive plants were also present in CLas -permissive hosts plus additional AAs in the latter class of plants. However, the relative composition of 18 commonly shared AAs varied between CLas -permissive hosts and non-permissive plants. Multivariate analysis with a partial least square discriminant methodology revealed a total of 12 AAs as major factors affecting CLas host status, of which seven were positively related to CLas tolerance/resistance and five positively associated with CLas susceptibility. Most of the AAs positively associated with CLas susceptibility were predominantly of the glutamate family, notably stressed-induced AAs such as arginine, GABA and proline. In contrast, AAs positively correlated with CLas tolerance/resistance were mainly of the serine family. Further analysis revealed that whereas the relative proportions of AAs positively associated with CLas susceptibility did not vary with host developmental stages, those associated with CLas tolerance/resistance increased with flush shoot maturity. Significantly, the proline-to-glycine ratio was determined to be an important discriminating factor for CLas permissivity with higher values characteristic of CLas -permissive hosts. This ratio could be exploited as a biomarker in HLB-resistance breeding programs. PMID:29236706

Novel Permissive Cell Lines for Complete Propagation of Hepatitis C Virus

PubMed Central

Shiokawa, Mai; Fukuhara, Takasuke; Ono, Chikako; Yamamoto, Satomi; Okamoto, Toru; Watanabe, Noriyuki; Wakita, Takaji

2014-01-01

ABSTRACT Hepatitis C virus (HCV) is a major etiologic agent of chronic liver diseases. Although the HCV life cycle has been clarified by studying laboratory strains of HCV derived from the genotype 2a JFH-1 strain (cell culture-adapted HCV [HCVcc]), the mechanisms of particle formation have not been elucidated. Recently, we showed that exogenous expression of a liver-specific microRNA, miR-122, in nonhepatic cell lines facilitates efficient replication but not particle production of HCVcc, suggesting that liver-specific host factors are required for infectious particle formation. In this study, we screened human cancer cell lines for expression of the liver-specific α-fetoprotein by using a cDNA array database and identified liver-derived JHH-4 cells and stomach-derived FU97 cells, which express liver-specific host factors comparable to Huh7 cells. These cell lines permit not only replication of HCV RNA but also particle formation upon infection with HCVcc, suggesting that hepatic differentiation participates in the expression of liver-specific host factors required for HCV propagation. HCV inhibitors targeting host and viral factors exhibited different antiviral efficacies between Huh7 and FU97 cells. Furthermore, FU97 cells exhibited higher susceptibility for propagation of HCVcc derived from the JFH-2 strain than Huh7 cells. These results suggest that hepatic differentiation participates in the expression of liver-specific host factors required for complete propagation of HCV. IMPORTANCE Previous studies have shown that liver-specific host factors are required for efficient replication of HCV RNA and formation of infectious particles. In this study, we screened human cancer cell lines for expression of the liver-specific α-fetoprotein by using a cDNA array database and identified novel permissive cell lines for complete propagation of HCVcc without any artificial manipulation. In particular, gastric cancer-derived FU97 cells exhibited a much higher susceptibility to HCVcc/JFH-2 infection than observed in Huh7 cells, suggesting that FU97 cells would be useful for further investigation of the HCV life cycle, as well as the development of therapeutic agents for chronic hepatitis C. PMID:24599999

Virus-Induced Necrosis Is a Consequence of Direct Protein-Protein Interaction between a Viral RNA-Silencing Suppressor and a Host Catalase[C][W

PubMed Central

Inaba, Jun-ichi; Kim, Bo Min; Shimura, Hanako; Masuta, Chikara

2011-01-01

Many plant host factors are known to interact with viral proteins during pathogenesis, but how a plant virus induces a specific disease symptom still needs further research. A lily strain of Cucumber mosaic virus (CMV-HL) can induce discrete necrotic spots on infected Arabidopsis (Arabidopsis thaliana) plants; other CMV strains can induce similar spots, but they are not as distinct as those induced by CMV-HL. The CMV 2b protein (2b), a known RNA-silencing suppressor, is involved in viral movement and symptom induction. Using in situ proximity ligation assay immunostaining and the protoplast assays, we report here that CMV 2b interacts directly with Catalase3 (CAT3) in infected tissues, a key enzyme in the breakdown of toxic hydrogen peroxide. Interestingly, CAT3, normally localized in the cytoplasm (glyoxysome), was recruited to the nucleus by an interaction between 2b and CAT3. Although overexpression of CAT3 in transgenic plants decreased the accumulation of CMV and delayed viral symptom development to some extent, 2b seems to neutralize the cellular catalase contributing to the host defense response, thus favoring viral infection. Our results thus provide evidence that, in addition to altering the type of symptom by disturbing microRNA pathways, 2b can directly bind to a host factor that is important in scavenging cellular hydrogen peroxide and thus interfere specifically with that host factor, leading to the induction of a specific necrosis. PMID:21622812

Virus-induced necrosis is a consequence of direct protein-protein interaction between a viral RNA-silencing suppressor and a host catalase.

PubMed

Inaba, Jun-ichi; Kim, Bo Min; Shimura, Hanako; Masuta, Chikara

2011-08-01

Many plant host factors are known to interact with viral proteins during pathogenesis, but how a plant virus induces a specific disease symptom still needs further research. A lily strain of Cucumber mosaic virus (CMV-HL) can induce discrete necrotic spots on infected Arabidopsis (Arabidopsis thaliana) plants; other CMV strains can induce similar spots, but they are not as distinct as those induced by CMV-HL. The CMV 2b protein (2b), a known RNA-silencing suppressor, is involved in viral movement and symptom induction. Using in situ proximity ligation assay immunostaining and the protoplast assays, we report here that CMV 2b interacts directly with Catalase3 (CAT3) in infected tissues, a key enzyme in the breakdown of toxic hydrogen peroxide. Interestingly, CAT3, normally localized in the cytoplasm (glyoxysome), was recruited to the nucleus by an interaction between 2b and CAT3. Although overexpression of CAT3 in transgenic plants decreased the accumulation of CMV and delayed viral symptom development to some extent, 2b seems to neutralize the cellular catalase contributing to the host defense response, thus favoring viral infection. Our results thus provide evidence that, in addition to altering the type of symptom by disturbing microRNA pathways, 2b can directly bind to a host factor that is important in scavenging cellular hydrogen peroxide and thus interfere specifically with that host factor, leading to the induction of a specific necrosis.

SUMO1 depletion prevents lipid droplet accumulation and HCV replication.

PubMed

Akil, Abdellah; Wedeh, Ghaith; Zahid Mustafa, Mohammad; Gassama-Diagne, Ama

2016-01-01

Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a strain, which produces infectious particles and recapitulates all the steps of the HCV life cycle. We observed that SUMO1 is upregulated in Huh7.5 infected cells. Reciprocally, SUMO1 was found to regulate the expression of viral core protein. Moreover, knockdown of SUMO1 using specific siRNA influenced the accumulation of lipid droplets and reduced HCV replication as measured by qRT-PCR. Thus, we identify SUMO1 as a key host factor required for HCV replication. To our knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection. Our report provides a meaningful insight into how HCV replicates and interacts with host proteins and is of significant importance for the field of HCV and RNA viruses.

Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.

PubMed

Blask, David E; Dauchy, Robert T; Dauchy, Erin M; Mao, Lulu; Hill, Steven M; Greene, Michael W; Belancio, Victoria P; Sauer, Leonard A; Davidson, Leslie

2014-01-01

The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

Legionella pathogenicity: genome structure, regulatory networks and the host cell response.

PubMed

Steinert, Michael; Heuner, Klaus; Buchrieser, Carmen; Albert-Weissenberger, Christiane; Glöckner, Gernot

2007-11-01

Legionella spp. the causative agent of Legionnaires' disease is naturally found in fresh water where the bacteria parasitize intracellularly within protozoa. Upon aerosol formation via man-made water systems, Legionella can enter the human lung and cause a severe form of pneumonia. Here we review results from systematic comparative genome analysis of Legionella species with different pathogenic potentials. The complete genomes reveal that horizontal gene transfer has played an important role during the evolution of Legionella and indicate the importance of secretion machineries for the intracellular lifestyle of this pathogen. Moreover, we highlight recent findings on the in vivo transcriptional program of L. pneumophila and the regulatory networks involved in the biphasic life cycle. In order to understand how Legionella effectively subvert host cell functions for its own benefit the transcriptional host cell response upon infection of the model amoeba Dictyostelium discoideum was studied. The use of this model organism made it possible to develop a roadmap of host cell factors which significantly contribute to the uptake of L. pneumophila and the establishment of an ER-associated replicative vacuole.

The Influence of Programmed Cell Death in Myeloid Cells on Host Resilience to Infection with Legionella pneumophila or Streptococcus pyogenes

PubMed Central

Gamradt, Pia; Xu, Yun; Gratz, Nina; Duncan, Kellyanne; Kobzik, Lester; Högler, Sandra; Decker, Thomas

2016-01-01

Pathogen clearance and host resilience/tolerance to infection are both important factors in surviving an infection. Cells of the myeloid lineage play important roles in both of these processes. Neutrophils, monocytes, macrophages, and dendritic cells all have important roles in initiation of the immune response and clearance of bacterial pathogens. If these cells are not properly regulated they can result in excessive inflammation and immunopathology leading to decreased host resilience. Programmed cell death (PCD) is one possible mechanism that myeloid cells may use to prevent excessive inflammation. Myeloid cell subsets play roles in tissue repair, immune response resolution, and maintenance of homeostasis, so excessive PCD may also influence host resilience in this way. In addition, myeloid cell death is one mechanism used to control pathogen replication and dissemination. Many of these functions for PCD have been well defined in vitro, but the role in vivo is less well understood. We created a mouse that constitutively expresses the pro-survival B-cell lymphoma (bcl)-2 protein in myeloid cells (CD68(bcl2tg), thus decreasing PCD specifically in myeloid cells. Using this mouse model we explored the impact that decreased cell death of these cells has on infection with two different bacterial pathogens, Legionella pneumophila and Streptococcus pyogenes. Both of these pathogens target multiple cell death pathways in myeloid cells, and the expression of bcl2 resulted in decreased PCD after infection. We examined both pathogen clearance and host resilience and found that myeloid cell death was crucial for host resilience. Surprisingly, the decreased myeloid PCD had minimal impact on pathogen clearance. These data indicate that the most important role of PCD during infection with these bacteria is to minimize inflammation and increase host resilience, not to aid in the clearance or prevent the spread of the pathogen. PMID:27973535

A Host Susceptibility Gene, DR1, Facilitates Influenza A Virus Replication by Suppressing Host Innate Immunity and Enhancing Viral RNA Replication

PubMed Central

Hsu, Shih-Feng; Su, Wen-Chi; Jeng, King-Song

2015-01-01

ABSTRACT Influenza A virus (IAV) depends on cellular factors to complete its replication cycle; thus, investigation of the factors utilized by IAV may facilitate antiviral drug development. To this end, a cellular transcriptional repressor, DR1, was identified from a genome-wide RNA interference (RNAi) screen. Knockdown (KD) of DR1 resulted in reductions of viral RNA and protein production, demonstrating that DR1 acts as a positive host factor in IAV replication. Genome-wide transcriptomic analysis showed that there was a strong induction of interferon-stimulated gene (ISG) expression after prolonged DR1 KD. We found that beta interferon (IFN-β) was induced by DR1 KD, thereby activating the JAK-STAT pathway to turn on ISG expression, which led to a strong inhibition of IAV replication. This result suggests that DR1 in normal cells suppresses IFN induction, probably to prevent undesired cytokine production, but that this suppression may create a milieu that favors IAV replication once cells are infected. Furthermore, biochemical assays of viral RNA replication showed that DR1 KD suppressed viral RNA replication. We also showed that DR1 associated with all three subunits of the viral RNA-dependent RNA polymerase (RdRp) complex, indicating that DR1 may interact with individual components of the viral RdRp complex to enhance viral RNA replication. Thus, DR1 may be considered a novel host susceptibility gene for IAV replication via a dual mechanism, not only suppressing the host defense to indirectly favor IAV replication but also directly facilitating viral RNA replication. IMPORTANCE Investigations of virus-host interactions involved in influenza A virus (IAV) replication are important for understanding viral pathogenesis and host defenses, which may manipulate influenza virus infection or prevent the emergence of drug resistance caused by a high error rate during viral RNA replication. For this purpose, a cellular transcriptional repressor, DR1, was identified from a genome-wide RNAi screen as a positive regulator in IAV replication. In the current studies, we showed that DR1 suppressed the gene expression of a large set of host innate immunity genes, which indirectly facilitated IAV replication in the event of IAV infection. Besides this scenario, DR1 also directly enhanced the viral RdRp activity, likely through associating with individual components of the viral RdRp complex. Thus, DR1 represents a novel host susceptibility gene for IAV replication via multiple functions, not only suppressing the host defense but also enhancing viral RNA replication. DR1 may be a potential target for drug development against influenza virus infection. PMID:25589657

Influenza A Virus Dysregulates Host Histone Deacetylase 1 That Inhibits Viral Infection in Lung Epithelial Cells.

PubMed

Nagesh, Prashanth Thevkar; Husain, Matloob

2016-05-01

Viruses dysregulate the host factors that inhibit virus infection. Here, we demonstrate that human enzyme, histone deacetylase 1 (HDAC1) is a new class of host factor that inhibits influenza A virus (IAV) infection, and IAV dysregulates HDAC1 to efficiently replicate in epithelial cells. A time-dependent decrease in HDAC1 polypeptide level was observed in IAV-infected cells, reducing to <50% by 24 h of infection. A further depletion (97%) of HDAC1 expression by RNA interference increased the IAV growth kinetics, increasing it by >3-fold by 24 h and by >6-fold by 48 h of infection. Conversely, overexpression of HDAC1 decreased the IAV infection by >2-fold. Likewise, a time-dependent decrease in HDAC1 activity, albeit with slightly different kinetics to HDAC1 polypeptide reduction, was observed in infected cells. Nevertheless, a further inhibition of deacetylase activity increased IAV infection in a dose-dependent manner. HDAC1 is an important host deacetylase and, in addition to its role as a transcription repressor, HDAC1 has been lately described as a coactivator of type I interferon response. Consistent with this property, we found that inhibition of deacetylase activity either decreased or abolished the phosphorylation of signal transducer and activator of transcription I (STAT1) and expression of interferon-stimulated genes, IFITM3, ISG15, and viperin in IAV-infected cells. Furthermore, the knockdown of HDAC1 expression in infected cells decreased viperin expression by 58% and, conversely, the overexpression of HDAC1 increased it by 55%, indicating that HDAC1 is a component of IAV-induced host type I interferon antiviral response. Influenza A virus (IAV) continues to significantly impact global public health by causing regular seasonal epidemics, occasional pandemics, and zoonotic outbreaks. IAV is among the successful human viral pathogens that has evolved various strategies to evade host defenses, prevent the development of a universal vaccine, and acquire antiviral drug resistance. A comprehensive knowledge of IAV-host interactions is needed to develop a novel and alternative anti-IAV strategy. Host produces a variety of factors that are able to fight IAV infection by employing various mechanisms. However, the full repertoire of anti-IAV host factors and their antiviral mechanisms has yet to be identified. We have identified here a new host factor, histone deacetylase 1 (HDAC1) that inhibits IAV infection. We demonstrate that HDAC1 is a component of host innate antiviral response against IAV, and IAV undermines HDAC1 to limit its role in antiviral response. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Eilat virus host range restriction is present at multiple levels of the virus life cycle.

PubMed

Nasar, Farooq; Gorchakov, Rodion V; Tesh, Robert B; Weaver, Scott C

2015-01-15

Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. This ability of most alphaviruses to infect arthropods and vertebrates is essential for their maintenance in nature. Recently, a new alphavirus, Eilat virus (EILV), was described, and in contrast to all other mosquito-borne viruses, it is unable to replicate in vertebrate cell lines. Investigations into the nature of its host range restriction showed the inability of genomic EILV RNA to replicate in vertebrate cells. Here, we investigated whether the EILV host range restriction is present at the entry level and further explored the viral factors responsible for the lack of genomic RNA replication. Utilizing Sindbis virus (SINV) and EILV chimeras, we show that the EILV vertebrate host range restriction is also manifested at the entry level. Furthermore, the EILV RNA replication restriction is independent of the 3' untranslated genome region (UTR). Complementation experiments with SINV suggested that RNA replication is restricted by the inability of the EILV nonstructural proteins to form functional replicative complexes. These data demonstrate that the EILV host range restriction is multigenic, involving at least one gene from both nonstructural protein (nsP) and structural protein (sP) open reading frames (ORFs). As EILV groups phylogenetically within the mosquito-borne virus clade of pathogenic alphaviruses, our findings have important evolutionary implications for arboviruses. Our work explores the nature of host range restriction of the first "mosquito-only alphavirus," EILV. EILV is related to pathogenic mosquito-borne viruses (Eastern equine encephalitis virus [EEEV], Western equine encephalitis virus [WEEV], Venezuelan equine encephalitis virus [VEEV], and Chikungunya virus [CHIKV]) that cause severe disease in humans. Our data demonstrate that EILV is restricted both at entry and genomic RNA replication levels in vertebrate cells. These findings have important implications for arbovirus evolution and will help elucidate the viral factors responsible for the broad host range of pathogenic mosquito-borne alphaviruses, facilitate vaccine development, and inform potential strategies to reduce/prevent alphavirus transmission. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of host migration, diversity and aquaculture on sea lice threats to Pacific salmon populations.

PubMed

Krkosek, Martin; Gottesfeld, Allen; Proctor, Bart; Rolston, Dave; Carr-Harris, Charmaine; Lewis, Mark A

2007-12-22

Animal migrations can affect disease dynamics. One consequence of migration common to marine fish and invertebrates is migratory allopatry-a period of spatial separation between adult and juvenile hosts, which is caused by host migration and which prevents parasite transmission from adult to juvenile hosts. We studied this characteristic for sea lice (Lepeophtheirus salmonis and Caligus clemensi) and pink salmon (Oncorhynchus gorbuscha) from one of the Canada's largest salmon stocks. Migratory allopatry protects juvenile salmon from L. salmonis for two to three months of early marine life (2-3% prevalence). In contrast, host diversity facilitates access for C. clemensi to juvenile salmon (8-20% prevalence) but infections appear ephemeral. Aquaculture can augment host abundance and diversity and increase parasite exposure of wild juvenile fish. An empirically parametrized model shows high sensitivity of salmon populations to increased L. salmonis exposure, predicting population collapse at one to five motile L. salmonis per juvenile pink salmon. These results characterize parasite threats of salmon aquaculture to wild salmon populations and show how host migration and diversity are important factors affecting parasite transmission in the oceans.

Advances in plant virus evolution: translating evolutionary insights into better disease management.

PubMed

Acosta-Leal, R; Duffy, S; Xiong, Z; Hammond, R W; Elena, S F

2011-10-01

Recent studies in plant virus evolution are revealing that genetic structure and behavior of virus and viroid populations can explain important pathogenic properties of these agents, such as host resistance breakdown, disease severity, and host shifting, among others. Genetic variation is essential for the survival of organisms. The exploration of how these subcellular parasites generate and maintain a certain frequency of mutations at the intra- and inter-host levels is revealing novel molecular virus-plant interactions. They emphasize the role of host environment in the dynamic genetic composition of virus populations. Functional genomics has identified host factors that are transcriptionally altered after virus infections. The analyses of these data by means of systems biology approaches are uncovering critical plant genes specifically targeted by viruses during host adaptation. Also, a next-generation resequencing approach of a whole virus genome is opening new avenues to study virus recombination and the relationships between intra-host virus composition and pathogenesis. Altogether, the analyzed data indicate that systematic disruption of some specific parameters of evolving virus populations could lead to more efficient ways of disease prevention, eradication, or tolerable virus-plant coexistence.

Genome characterization and population genetic structure of the zoonotic pathogen, Streptococcus canis

PubMed Central

2012-01-01

Background Streptococcus canis is an important opportunistic pathogen of dogs and cats that can also infect a wide range of additional mammals including cows where it can cause mastitis. It is also an emerging human pathogen. Results Here we provide characterization of the first genome sequence for this species, strain FSL S3-227 (milk isolate from a cow with an intra-mammary infection). A diverse array of putative virulence factors was encoded by the S. canis FSL S3-227 genome. Approximately 75% of these gene sequences were homologous to known Streptococcal virulence factors involved in invasion, evasion, and colonization. Present in the genome are multiple potentially mobile genetic elements (MGEs) [plasmid, phage, integrative conjugative element (ICE)] and comparison to other species provided convincing evidence for lateral gene transfer (LGT) between S. canis and two additional bovine mastitis causing pathogens (Streptococcus agalactiae, and Streptococcus dysgalactiae subsp. dysgalactiae), with this transfer possibly contributing to host adaptation. Population structure among isolates obtained from Europe and USA [bovine = 56, canine = 26, and feline = 1] was explored. Ribotyping of all isolates and multi locus sequence typing (MLST) of a subset of the isolates (n = 45) detected significant differentiation between bovine and canine isolates (Fisher exact test: P = 0.0000 [ribotypes], P = 0.0030 [sequence types]), suggesting possible host adaptation of some genotypes. Concurrently, the ancestral clonal complex (54% of isolates) occurred in many tissue types, all hosts, and all geographic locations suggesting the possibility of a wide and diverse niche. Conclusion This study provides evidence highlighting the importance of LGT in the evolution of the bacteria S. canis, specifically, its possible role in host adaptation and acquisition of virulence factors. Furthermore, recent LGT detected between S. canis and human bacteria (Streptococcus urinalis) is cause for concern, as it highlights the possibility for continued acquisition of human virulence factors for this emerging zoonotic pathogen. PMID:23244770

[Proboscis worm, Echinorhynchus gadi (Zoega) from a relict cod of Lake Mogil'noye].

PubMed

Kulachkova, V G; Timofeeva, T A

1977-01-01

Data on the extensiveness and intensity of infection of Kildin island cod with Echinorhynchus gadi in various seasons are given. E. gadi was proved to have a one-year life cycle and Gammarus duebeni as an intermediate host in the lake. A change of the parasite generations occurs in late summer--autumn. A high extensiveness (100%) and intensity of Kildin cod infection with E. gadi depends on the feeding habits (monophagy) and narrow distribution range of the host. Infection intensity is directly correlated with the fish age. Selfregulation of the parasite quantity in the host's intenstine is an important factor affecting the existence of E. gadi population in Lake Mogilnoye.

A System Biology Perspective on Environment-Host-Microbe Interactions.

PubMed

Chen, Lianmin; Garmaeva, Sanzhima; Zherankova, Alexandra; Fu, Jingyuan; Wijmenga, Cisca

2018-04-16

A vast, complex and dynamic consortium of microorganisms known as the gut microbiome colonizes the human gut. Over the past few decades we have developed an increased awareness of its important role in human health. In this review we discuss the role of the gut microbiome in complex diseases and the possible causal scenarios behind its interactions with the host genome and environmental factors. We then propose a new analysis framework that combines a systems biology approach, cross-kingdom integration of multiple levels of omics data, and innovative in vitro models to yield an integrated picture of human host-microbe interactions. This new framework will lay the foundation for the development of the next phase in personalized medicine.

Unraveling the environmental and genetic interactions in atherosclerosis: Central role of the gut microbiota

PubMed Central

Org, Elin; Mehrabian, Margarete; Lusis, Aldons J.

2015-01-01

Recent studies have convincingly linked gut microbiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gut microbiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gut microbiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD. PMID:26071662

The genome of Eimeria falciformis--reduction and specialization in a single host apicomplexan parasite.

PubMed

Heitlinger, Emanuel; Spork, Simone; Lucius, Richard; Dieterich, Christoph

2014-08-20

The phylum Apicomplexa comprises important unicellular human parasites such as Toxoplasma and Plasmodium. Eimeria is the largest and most diverse genus of apicomplexan parasites and some species of the genus are the causative agent of coccidiosis, a disease economically devastating in poultry. We report a complete genome sequence of the mouse parasite Eimeria falciformis. We assembled and annotated the genome sequence to study host-parasite interactions in this understudied genus in a model organism host. The genome of E. falciformis is 44 Mb in size and contains 5,879 predicted protein coding genes. Comparative analysis of E. falciformis with Toxoplasma gondii shows an emergence and diversification of gene families associated with motility and invasion mainly at the level of the Coccidia. Many rhoptry kinases, among them important virulence factors in T. gondii, are absent from the E. falciformis genome. Surface antigens are divergent between Eimeria species. Comparisons with T. gondii showed differences between genes involved in metabolism, N-glycan and GPI-anchor synthesis. E. falciformis possesses a reduced set of transmembrane transporters and we suggest an altered mode of iron uptake in the genus Eimeria. Reduced diversity of genes required for host-parasite interaction and transmembrane transport allow hypotheses on host adaptation and specialization of a single host parasite. The E. falciformis genome sequence sheds light on the evolution of the Coccidia and helps to identify determinants of host-parasite interaction critical for drug and vaccine development.

The Effect and Relative Importance of Neutral Genetic Diversity for Predicting Parasitism Varies across Parasite Taxa

PubMed Central

Ruiz-López, María José; Monello, Ryan J.; Gompper, Matthew E.; Eggert, Lori S.

2012-01-01

Understanding factors that determine heterogeneity in levels of parasitism across individuals is a major challenge in disease ecology. It is known that genetic makeup plays an important role in infection likelihood, but the mechanism remains unclear as does its relative importance when compared to other factors. We analyzed relationships between genetic diversity and macroparasites in outbred, free-ranging populations of raccoons (Procyon lotor). We measured heterozygosity at 14 microsatellite loci and modeled the effects of both multi-locus and single-locus heterozygosity on parasitism using an information theoretic approach and including non-genetic factors that are known to influence the likelihood of parasitism. The association of genetic diversity and parasitism, as well as the relative importance of genetic diversity, differed by parasitic group. Endoparasite species richness was better predicted by a model that included genetic diversity, with the more heterozygous hosts harboring fewer endoparasite species. Genetic diversity was also important in predicting abundance of replete ticks (Dermacentor variabilis). This association fit a curvilinear trend, with hosts that had either high or low levels of heterozygosity harboring fewer parasites than those with intermediate levels. In contrast, genetic diversity was not important in predicting abundance of non-replete ticks and lice (Trichodectes octomaculatus). No strong single-locus effects were observed for either endoparasites or replete ticks. Our results suggest that in outbred populations multi-locus diversity might be important for coping with parasitism. The differences in the relationships between heterozygosity and parasitism for the different parasites suggest that the role of genetic diversity varies with parasite-mediated selective pressures. PMID:23049796

[Riddles in human tuberculous infection].

PubMed

Tsuyuguchi, I

2000-10-01

Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. However, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy. There are several riddles or enigmas in the natural history of M. tuberculosis infection in humans. Some of them are as follows: 1. What is the virulence of M. tuberculosis? 2. How does M. tuberculosis persist dormant within the host? 3. What determines the development of disease from remaining healthy after infection with M. tuberculosis? 4. What is the mechanism of "endogenous reactivation" of dormant M. tuberculosis within the host? 5. Can we expect more potent anti-TB vaccine than BCG in near future? Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect human TB at all. What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exerts its detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-alpha. How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vaccine than the currently used BCG.

Influence of Stress and Antibiotic Resistance on Cell-Length Distribution in Mycobacterium tuberculosis Clinical Isolates

PubMed Central

Vijay, Srinivasan; Vinh, Dao N.; Hai, Hoang T.; Ha, Vu T. N.; Dung, Vu T. M.; Dinh, Tran D.; Nhung, Hoang N.; Tram, Trinh T. B.; Aldridge, Bree B.; Hanh, Nguyen T.; Thu, Do D. A.; Phu, Nguyen H.; Thwaites, Guy E.; Thuong, Nguyen T. T.

2017-01-01

Mycobacterial cellular variations in growth and division increase heterogeneity in cell length, possibly contributing to cell-to-cell variation in host and antibiotic stress tolerance. This may be one of the factors influencing Mycobacterium tuberculosis persistence to antibiotics. Tuberculosis (TB) is a major public health problem in developing countries, antibiotic persistence, and emergence of antibiotic resistance further complicates this problem. We wanted to investigate the factors influencing cell-length distribution in clinical M. tuberculosis strains. In parallel we examined M. tuberculosis cell-length distribution in a large set of clinical strains (n = 158) from ex vivo sputum samples, in vitro macrophage models, and in vitro cultures. Our aim was to understand the influence of clinically relevant factors such as host stresses, M. tuberculosis lineages, antibiotic resistance, antibiotic concentrations, and disease severity on the cell size distribution in clinical M. tuberculosis strains. Increased cell size and cell-to-cell variation in cell length were associated with bacteria in sputum and infected macrophages rather than liquid culture. Multidrug-resistant (MDR) strains displayed increased cell length heterogeneity compared to sensitive strains in infected macrophages and also during growth under rifampicin (RIF) treatment. Importantly, increased cell length was also associated with pulmonary TB disease severity. Supporting these findings, individual host stresses, such as oxidative stress and iron deficiency, increased cell-length heterogeneity of M. tuberculosis strains. In addition we also observed synergism between host stress and RIF treatment in increasing cell length in MDR-TB strains. This study has identified some clinical factors contributing to cell-length heterogeneity in clinical M. tuberculosis strains. The role of these cellular adaptations to host and antibiotic tolerance needs further investigation. PMID:29209302

Comparative genomic analysis of coffee-infecting Xylella fastidiosa strains isolated from Brazil.

PubMed

Barbosa, Deibs; Alencar, Valquíria Campos; Santos, Daiene Souza; de Freitas Oliveira, Ana Cláudia; de Souza, Alessandra A; Coletta-Filho, Helvecio D; de Oliveira, Regina Souza; Nunes, Luiz R

2015-05-01

Strains of Xylella fastidiosa constitute a complex group of bacteria that develop within the xylem of many plant hosts, causing diseases of significant economic importance, such as Pierce's disease in North American grapevines and citrus variegated chlorosis in Brazil. X. fastidiosa has also been obtained from other host plants, in direct correlation with the development of diseases, as in the case of coffee leaf scorch (CLS)--a disease with potential to cause severe economic losses to the Brazilian coffee industry. This paper describes a thorough genomic characterization of coffee-infecting X. fastidiosa strains, initially performed through a microarray-based approach, which demonstrated that CLS strains could be subdivided in two phylogenetically distinct subgroups. Whole-genomic sequencing of two of these bacteria (one from each subgroup) allowed identification of ORFs and horizontally transferred elements (HTEs) that were specific to CLS-related X. fastidiosa strains. Such analyses confirmed the size and importance of HTEs as major mediators of chromosomal evolution amongst these bacteria, and allowed identification of differences in gene content, after comparisons were made with previously sequenced X. fastidiosa strains, isolated from alternative hosts. Although direct experimentation still needs to be performed to elucidate the biological consequences associated with such differences, it was interesting to verify that CLS-related bacteria display variations in genes that produce toxins, as well as surface-related factors (such as fimbrial adhesins and LPS) that have been shown to be involved with recognition of specific host factors in different pathogenic bacteria. © 2015 The Authors.

Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries

PubMed Central

Shames, Stephanie R.; Liu, Luying; Havey, James C.; Schofield, Whitman B.; Goodman, Andrew L.; Roy, Craig R.

2017-01-01

Legionella pneumophila is the causative agent of a severe pneumonia called Legionnaires’ disease. A single strain of L. pneumophila encodes a repertoire of over 300 different effector proteins that are delivered into host cells by the Dot/Icm type IV secretion system during infection. The large number of L. pneumophila effectors has been a limiting factor in assessing the importance of individual effectors for virulence. Here, a transposon insertion sequencing technology called INSeq was used to analyze replication of a pool of effector mutants in parallel both in a mouse model of infection and in cultured host cells. Loss-of-function mutations in genes encoding effector proteins resulted in host-specific or broad virulence phenotypes. Screen results were validated for several effector mutants displaying different virulence phenotypes using genetic complementation studies and infection assays. Specifically, loss-of-function mutations in the gene encoding LegC4 resulted in enhanced L. pneumophila in the lungs of infected mice but not within cultured host cells, which indicates LegC4 augments bacterial clearance by the host immune system. The effector proteins RavY and Lpg2505 were important for efficient replication within both mammalian and protozoan hosts. Further analysis of Lpg2505 revealed that this protein functions as a metaeffector that counteracts host cytotoxicity displayed by the effector protein SidI. Thus, this study identified a large cohort of effectors that contribute to L. pneumophila virulence positively or negatively and has demonstrated regulation of effector protein activities by cognate metaeffectors as being critical for host pathogenesis. PMID:29133401

Comparisons of host specificity in feather louse genera (Insecta: Phthiraptera: Philopteridae) parasitizing gulls (Aves: Laridae: Larus).

PubMed

Yamagishi, Ayaka; Yao, Izumi; Johnson, Kevin P; Yoshizawa, Kazunori

2014-06-01

Data from gene sequences and morphological structures were collected for the gull feather lice, Saemundssonia lari, Quadraceps punctatus, and Q. ornatus, parasitizing Larus crassirostris and L. schistisagus. Saemundssonia lari was collected from both gull species, and no detectable morphological and genetic differences were found between lice collected from the two different hosts. In contrast, Q. punctatus was only collected from L. crassirostris, whereas Q. ornatus was only collected from L. schistisagus. The two Quadraceps species were genetically highly divergent, and body-size differences corresponding to the gull's body size (Harrison's rule) were also detected between them. Both Quadraceps species were collected from the interbarb of the remex or rectrix, and a match in body size between the louse and the interbarb space may be important in escape from host preening defenses. In contrast, Saemundssonia is a head louse, inhabiting the finer feathers of the head and neck, which the bird cannot preen. A close match to host body size may be less important for lice in the head microhabitat. The differences in the pattern of host-specificity between Saemundssonia and Quadraceps on the two focal host species of this study were probably due to their different microhabitat preferences. More broadly, comparisons of the gene sequences of S. lari and Q. punctatus to those from other gull hosts showed that genetically almost undifferentiated populations of both species were distributed on wide range of gull species. Frequent interspecific hybridization of gulls is one possible factor that may allow these lice to maintain gene flow across multiple host species.

Host Plant Adaptation in Drosophila mettleri Populations

PubMed Central

Castrezana, Sergio; Bono, Jeremy M.

2012-01-01

The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total). We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea) for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp.) in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts. PMID:22493678

Host plant adaptation in Drosophila mettleri populations.

PubMed

Castrezana, Sergio; Bono, Jeremy M

2012-01-01

The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total). We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea) for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp.) in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts.

Seasonal, spatial, and maternal effects on gut microbiome in wild red squirrels.

PubMed

Ren, Tiantian; Boutin, Stan; Humphries, Murray M; Dantzer, Ben; Gorrell, Jamieson C; Coltman, David W; McAdam, Andrew G; Wu, Martin

2017-12-21

Our understanding of gut microbiota has been limited primarily to findings from human and laboratory animals, but what shapes the gut microbiota in nature remains largely unknown. To fill this gap, we conducted a comprehensive study of gut microbiota of a well-studied North American red squirrel (Tamiasciurus hudsonicus) population. Red squirrels are territorial, solitary, and live in a highly seasonal environment and therefore represent a very attractive system to study factors that drive the temporal and spatial dynamics of gut microbiota. For the first time, this study revealed significant spatial patterns of gut microbiota within a host population, suggesting limited dispersal could play a role in shaping and maintaining the structure of gut microbial communities. We also found a remarkable seasonal rhythm in red squirrel's gut microbial composition manifested by a tradeoff between relative abundance of two genera Oscillospira and Corpococcus and clearly associated with seasonal variation in diet availability. Our results show that in nature, environmental factors exert a much stronger influence on gut microbiota than host-associated factors including age and sex. Despite strong environmental effects, we found clear evidence of individuality and maternal effects, but host genetics did not seem to be a significant driver of the gut microbial communities in red squirrels. Taken together, the results of this study emphasize the importance of external ecological factors rather than host attributes in driving temporal and spatial patterns of gut microbiota in natural environment.

Dual RNA-Sequencing of Eucalyptus nitens during Phytophthora cinnamomi Challenge Reveals Pathogen and Host Factors Influencing Compatibility

PubMed Central

Meyer, Febé E.; Shuey, Louise S.; Naidoo, Sitha; Mamni, Thandekile; Berger, Dave K.; Myburg, Alexander A.; van den Berg, Noëlani; Naidoo, Sanushka

2016-01-01

Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers, and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1). Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR) genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets, and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction. PMID:26973660

Complement Evasion by Pathogenic Leptospira.

PubMed

Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

2016-01-01

Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira . Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira , have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host.

Complement Evasion by Pathogenic Leptospira

PubMed Central

Fraga, Tatiana Rodrigues; Isaac, Lourdes; Barbosa, Angela Silva

2016-01-01

Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira. Pathogenic microorganisms, notably those which reach the blood circulation such as Leptospira, have evolved multiple strategies to escape the host complement system, which is important for innate and acquired immunity. Leptospira avoid complement-mediated killing through: (i) recruitment of host complement regulators; (ii) acquisition of host proteases that cleave complement proteins on the bacterial surface; and, (iii) secretion of proteases that inactivate complement proteins in the Leptospira surroundings. The recruitment of host soluble complement regulatory proteins includes the acquisition of Factor H (FH) and FH-like-1 (alternative pathway), C4b-binding protein (C4BP) (classical and lectin pathways), and vitronectin (Vn) (terminal pathway). Once bound to the leptospiral surface, FH and C4BP retain cofactor activity of Factor I in the cleavage of C3b and C4b, respectively. Vn acquisition by leptospires may result in terminal pathway inhibition by blocking C9 polymerization. The second evasion mechanism lies in plasminogen (PLG) binding to the leptospiral surface. In the presence of host activators, PLG is converted to enzymatically active plasmin, which is able to degrade C3b, C4b, and C5 at the surface of the pathogen. A third strategy used by leptospires to escape from complement system is the active secretion of proteases. Pathogenic, but not saprophytic leptospires, are able to secrete metalloproteases that cleave C3 (central complement molecule), Factor B (alternative pathway), and C4 and C2 (classical and lectin pathways). The purpose of this review is to fully explore these complement evasion mechanisms, which act together to favor Leptospira survival and multiplication in the host. PMID:28066433

Characterization of the Host Response to Pichinde Virus Infection in the Syrian Golden Hamster by Species-Specific Kinome Analysis*

PubMed Central

Falcinelli, Shane; Gowen, Brian B.; Trost, Brett; Napper, Scott; Kusalik, Anthony; Johnson, Reed F.; Safronetz, David; Prescott, Joseph; Wahl-Jensen, Victoria; Jahrling, Peter B.; Kindrachuk, Jason

2015-01-01

The Syrian golden hamster has been increasingly used to study viral hemorrhagic fever (VHF) pathogenesis and countermeasure efficacy. As VHFs are a global health concern, well-characterized animal models are essential for both the development of therapeutics and vaccines as well as for increasing our understanding of the molecular events that underlie viral pathogenesis. However, the paucity of reagents or platforms that are available for studying hamsters at a molecular level limits the ability to extract biological information from this important animal model. As such, there is a need to develop platforms/technologies for characterizing host responses of hamsters at a molecular level. To this end, we developed hamster-specific kinome peptide arrays to characterize the molecular host response of the Syrian golden hamster. After validating the functionality of the arrays using immune agonists of defined signaling mechanisms (lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α), we characterized the host response in a hamster model of VHF based on Pichinde virus (PICV1) infection by performing temporal kinome analysis of lung tissue. Our analysis revealed key roles for vascular endothelial growth factor (VEGF), interleukin (IL) responses, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and Toll-like receptor (TLR) signaling in the response to PICV infection. These findings were validated through phosphorylation-specific Western blot analysis. Overall, we have demonstrated that hamster-specific kinome arrays are a robust tool for characterizing the species-specific molecular host response in a VHF model. Further, our results provide key insights into the hamster host response to PICV infection and will inform future studies with high-consequence VHF pathogens. PMID:25573744

Factors limiting the spread of the protective symbiont HAMILTONELLA DEFENSA in the aphid APHIS CRACCIVORA

USDA-ARS?s Scientific Manuscript database

Many insects are associated with heritable facultative symbionts that mediate important ecological interactions, including host protection against natural enemies. Despite such benefits, facultative symbionts are commonly found at intermediate frequencies in surveyed populations. The cowpea aphid,...

Biological Control of Olive Fruit Fly

USDA-ARS?s Scientific Manuscript database

Domestication of olive fruit, Olea europaea L., produced a better host for olive fruit fly, Bactrocera oleae (Gmelin), than wild olives, but fruit domestication reduced natural enemy efficiency. Important factors for selection of natural enemies for control of olive fruit fly include climate matchi...

The role of body size in host specificity: reciprocal transfer experiments with feather lice.

PubMed

Bush, Sarah E; Clayton, Dale H

2006-10-01

Although most parasites show at least some degree of host specificity, factors governing the evolution of specificity remain poorly understood. Many different groups of host-specific parasites show a striking correlation between parasite and host body size, suggesting that size reinforces specificity. We tested this hypothesis by measuring the relative fitness of host-specific feather lice transferred to pigeons and doves that differ in size by an order of magnitude. To test the general influence of size, we transferred unrelated groups of wing and body lice, which are specialized for different regions of the host. Lice were transferred in both directions, from a large native host species, the rock pigeon (Columba livia), to several progressively smaller hosts, and from a small native host species, the common ground dove (Columbina passerina), to several larger hosts. We measured the relative fitness (population size) of lice transferred to these novel host species after two louse generations. Neither wing lice nor body lice could survive on novel host species that were smaller in size than the native host. However, when host defense (preening behavior) was blocked, both groups survived and reproduced on all novel hosts tested. Thus, host defense interacted with host size to govern the ability of lice to establish on small hosts. Neither wing lice nor body lice could survive on larger hosts, even when preening was blocked. In summary, host size influenced the fitness of both types of feather lice, but through different mechanisms, depending on the direction of the transfer. Our results indicate that host switching is most likely between hosts of similar body size. This finding has important implications for studies of host-parasite coevolution at both the micro- and macroevolutionary scales.

Butterfly Larval Host Plant use in a Tropical Urban Context: Life History Associations, Herbivory, and Landscape Factors

PubMed Central

Tiple, Ashish D.; Khurad, Arun M.; Dennis, Roger L. H.

2011-01-01

This study examines butterfly larval host plants, herbivory and related life history attributes within Nagpur City, India. The larval host plants of 120 butterfly species are identified and their host specificity, life form, biotope, abundance and perennation recorded; of the 126 larval host plants, most are trees (49), with fewer herbs (43), shrubs (22), climbers (7) and stem parasites (2). They include 89 wild, 23 cultivated, 11 wild/cultivated and 3 exotic plant species; 78 are perennials, 43 annuals and 5 biannuals. Plants belonging to Poaceae and Fabaceae are most widely used by butterfly larvae. In addition to distinctions in host plant family affiliation, a number of significant differences between butterfly families have been identified in host use patterns: for life forms, biotopes, landforms, perennation, host specificity, egg batch size and ant associations. These differences arising from the development of a butterfly resource database have important implications for conserving butterfly species within the city area. Differences in overall butterfly population sizes within the city relate mainly to the number of host plants used, but other influences, including egg batch size and host specificity are identified. Much of the variation in population size is unaccounted for and points to the need to investigate larval host plant life history and strategies as population size is not simply dependent on host plant abundance. PMID:21864159

Predicting what helminth parasites a fish species should have using Parasite Co-occurrence Modeler (PaCo)

USGS Publications Warehouse

Strona, Giovanni; Lafferty, Kevin D.

2013-01-01

Fish pathologists are often interested in which parasites would likely be present in a particular host. Parasite Co-occurrence Modeler (PaCo) is a tool for identifying a list of parasites known from fish species that are similar ecologically, phylogenetically, and geographically to the host of interest. PaCo uses data from FishBase (maximum length, growth rate, life span, age at maturity, trophic level, phylogeny, and biogeography) to estimate compatibility between a target host and parasite species–genera from the major helminth groups (Acanthocephala, Cestoda, Monogenea, Nematoda, and Trematoda). Users can include any combination of host attributes in a model. These unique features make PaCo an innovative tool for addressing both theoretical and applied questions in parasitology. In addition to predicting the occurrence of parasites, PaCo can be used to investigate how host characteristics shape parasite communities. To test the performance of the PaCo algorithm, we created 12,400 parasite lists by applying any possible combination of model parameters (248) to 50 fish hosts. We then measured the relative importance of each parameter by assessing their frequency in the best models for each host. Host phylogeny and host geography were identified as the most important factors, with both present in 88% of the best models. Habitat (64%) was identified in more than half of the best models. Among ecological parameters, trophic level (41%) was the most relevant while life span (34%), growth rate (32%), maximum length (28%), and age at maturity (20%) were less commonly linked to best models. PaCo is free to use at www.purl.oclc.org/fishpest.

Predicting what helminth parasites a fish species should have using Parasite Co-occurrence Modeler (PaCo).

PubMed

Strona, Giovanni; Lafferty, Kevin D

2013-02-01

Fish pathologists are often interested in which parasites would likely be present in a particular host. Parasite Co-occurrence Modeler (PaCo) is a tool for identifying a list of parasites known from fish species that are similar ecologically, phylogenetically, and geographically to the host of interest. PaCo uses data from FishBase (maximum length, growth rate, life span, age at maturity, trophic level, phylogeny, and biogeography) to estimate compatibility between a target host and parasite species-genera from the major helminth groups (Acanthocephala, Cestoda, Monogenea, Nematoda, and Trematoda). Users can include any combination of host attributes in a model. These unique features make PaCo an innovative tool for addressing both theoretical and applied questions in parasitology. In addition to predicting the occurrence of parasites, PaCo can be used to investigate how host characteristics shape parasite communities. To test the performance of the PaCo algorithm, we created 12,400 parasite lists by applying any possible combination of model parameters (248) to 50 fish hosts. We then measured the relative importance of each parameter by assessing their frequency in the best models for each host. Host phylogeny and host geography were identified as the most important factors, with both present in 88% of the best models. Habitat (64%) was identified in more than half of the best models. Among ecological parameters, trophic level (41%) was the most relevant while life span (34%), growth rate (32%), maximum length (28%), and age at maturity (20%) were less commonly linked to best models. PaCo is free to use at www.purl.oclc.org/fishpest.

Legionella phospholipases implicated in virulence.

PubMed

Kuhle, Katja; Flieger, Antje

2013-01-01

Phospholipases are diverse enzymes produced in eukaryotic hosts and their bacterial pathogens. Several pathogen phospholipases have been identified as major virulence factors acting mainly in two different modes: on the one hand, they have the capability to destroy host membranes and on the other hand they are able to manipulate host signaling pathways. Reaction products of bacterial phospholipases may act as secondary messengers within the host and therefore influence inflammatory cascades and cellular processes, such as proliferation, migration, cytoskeletal changes as well as membrane traffic. The lung pathogen and intracellularly replicating bacterium Legionella pneumophila expresses a variety of phospholipases potentially involved in disease-promoting processes. So far, genes encoding 15 phospholipases A, three phospholipases C, and one phospholipase D have been identified. These cell-associated or secreted phospholipases may contribute to intracellular establishment, to egress of the pathogen from the host cell, and to the observed lung pathology. Due to the importance of phospholipase activities for host cell processes, it is conceivable that the pathogen enzymes may mimic or substitute host cell phospholipases to drive processes for the pathogen's benefit. The following chapter summarizes the current knowledge on the L. pneumophila phospholipases, especially their substrate specificity, localization, mode of secretion, and impact on host cells.

Spread of an introduced parasite across the Hawaiian archipelago independent of its introduced host

DOE PAGES

Gagne, Roderick B.; Hogan, J. Derek; McIntyre, Peter B.; ...

2014-11-11

1. Co-introductions of non-native parasites with non-native hosts can be a major driver of disease emergence in native species, but the conditions that promote the establishment and spread of nonnative parasites remain poorly understood. Here, we characterise the infection of a native host species by a non-native parasite relative to the distribution and density of the original non-native host species and a suite of organismal and environmental factors that have been associated with parasitism, but not commonly considered within a single system. 2. We examined the native Hawaiian goby Awaous stamineus across 23 catchments on five islands for infection bymore » the non-native nematode parasite Camallanus cotti. We used model selection to test whether parasite infection was associated with the genetic diversity, size and population density of native hosts, the distribution and density of non-native hosts, land use and water quality. 3. We found that the distribution of non-native C. cotti parasites has become decoupled from the non-native hosts that were primary vectors of introduction to the Hawaiian Islands. Although no single intrinsic or extrinsic factor was identified that best explains parasitism of A. stamineus by C. cotti, native host size, population density and water quality were consistently identified as influencing parasite intensity and prevalence. 4. The introduction of non-native species can indirectly influence native species through infection of co-introduced parasites. Here, we show that the effects of enemy addition can extend beyond the range of non-native hosts through the independent spread of non-native parasites. This suggests that control of non-native hosts is not sufficient to halt the spread of introduced parasites. Furthermore, designing importation regulations to prevent host parasite co-introductions can promote native species conservation, even in remote areas that may not seem susceptible to human influence.« less

Ecological determinants of avian malaria infections: An integrative analysis at landscape, mosquito and vertebrate community levels.

PubMed

Ferraguti, Martina; Martínez-de la Puente, Josué; Bensch, Staffan; Roiz, David; Ruiz, Santigo; Viana, Duarte S; Soriguer, Ramón C; Figuerola, Jordi

2018-05-01

Vector and host communities, as well as habitat characteristics, may have important but different impacts on the prevalence, richness and evenness of vector-borne parasites. We investigated the relative importance of (1) the mosquito community composition, (2) the vertebrate community composition and (3) landscape characteristics on the prevalence, richness and evenness of avian Plasmodium. We hypothesized that parasite prevalence will be more affected by vector-related parameters, while host parameters should be also important to explain Plasmodium richness and evenness. We sampled 2,588 wild house sparrows (Passer domesticus) and 340,829 mosquitoes, and we performed vertebrate censuses at 45 localities in the Southwest of Spain. These localities included urban, rural and natural landscapes that were characterized by several habitat variables. Twelve Plasmodium lineages were identified in house sparrows corresponding to three major clades. Variation partitioning showed that landscape characteristics explained the highest fraction of variation in all response variables (21.0%-44.8%). Plasmodium prevalence was in addition explained by vector-related variables (5.4%) and its interaction with landscape (10.2%). Parasite richness and evenness were mostly explained by vertebrate community-related variables. The structuring role of landscape characteristics in vector and host communities was a key factor in determining parasite prevalence, richness and evenness, although the role of each factor differed according to the parasite parameters studied. These results show that the biotic and abiotic contexts are important to explain the transmission dynamics of mosquito-borne pathogens in the wild. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.

A Friendly Relationship between Endophytic Fungi and Medicinal Plants: A Systematic Review

PubMed Central

Jia, Min; Chen, Ling; Xin, Hai-Liang; Zheng, Cheng-Jian; Rahman, Khalid; Han, Ting; Qin, Lu-Ping

2016-01-01

Endophytic fungi or endophytes exist widely inside the healthy tissues of living plants, and are important components of plant micro-ecosystems. Over the long period of evolution, some co-existing endophytes and their host plants have established a special relationship with one and another, which can significantly influence the formation of metabolic products in plants, then affect quality and quantity of crude drugs derived from medicinal plants. This paper will focus on the increasing knowledge of relationships between endophytic fungi and medicinal plants through reviewing of published research data obtained from the last 30 years. The analytical results indicate that the distribution and population structure of endophytes can be considerably affected by factors, such as the genetic background, age, and environmental conditions of their hosts. On the other hand, the endophytic fungi can also confer profound impacts on their host plants by enhancing their growth, increasing their fitness, strengthening their tolerances to abiotic and biotic stresses, and promoting their accumulation of secondary metabolites. All the changes are very important for the production of bioactive components in their hosts. Hence, it is essential to understand such relationships between endophytic fungi and their host medicinal plants. Such knowledge can be well exploited and applied for the production of better and more drugs from medicinal plants. PMID:27375610

Natal Host Plants Can Alter Herbivore Competition

PubMed Central

Pan, Huipeng; Preisser, Evan L.; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun

2016-01-01

Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore’s natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems. PMID:28030636

Bacteriophages encode factors required for protection in a symbiotic mutualism.

PubMed

Oliver, Kerry M; Degnan, Patrick H; Hunter, Martha S; Moran, Nancy A

2009-08-21

Bacteriophages are known to carry key virulence factors for pathogenic bacteria, but their roles in symbiotic bacteria are less well understood. The heritable symbiont Hamiltonella defensa protects the aphid Acyrthosiphon pisum from attack by the parasitoid Aphidius ervi by killing developing wasp larvae. In a controlled genetic background, we show that a toxin-encoding bacteriophage is required to produce the protective phenotype. Phage loss occurs repeatedly in laboratory-held H. defensa-infected aphid clonal lines, resulting in increased susceptibility to parasitism in each instance. Our results show that these mobile genetic elements can endow a bacterial symbiont with benefits that extend to the animal host. Thus, phages vector ecologically important traits, such as defense against parasitoids, within and among symbiont and animal host lineages.

Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention

PubMed Central

Jhang, Jia-Fong; Kuo, Hann-Chorng

2017-01-01

Recurrent urinary tract infection (UTI) might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market. PMID:28974905

Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5.

PubMed

Swale, Christopher; Monod, Alexandre; Tengo, Laura; Labaronne, Alice; Garzoni, Frédéric; Bourhis, Jean-Marie; Cusack, Stephen; Schoehn, Guy; Berger, Imre; Ruigrok, Rob W H; Crépin, Thibaut

2016-04-20

The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3'- and 5'-ends of the vRNA segment. The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex. We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5'-vRNA. In contrast, 3'-vRNA recognition critically depends on the PB2 N-terminal domain. Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5'-vRNA binding. Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.

Ecological and genetic determinants of plasmid distribution in Escherichia coli.

PubMed

Medaney, Frances; Ellis, Richard J; Raymond, Ben

2016-11-01

Bacterial plasmids are important carriers of virulence and antibiotic resistance genes. Nevertheless, little is known of the determinants of plasmid distribution in bacterial populations. Here the factors affecting the diversity and distribution of the large plasmids of Escherichia coli were explored in cattle grazing on semi-natural grassland, a set of populations with low frequencies of antibiotic resistance genes. Critically, the population genetic structure of bacterial hosts was chararacterized. This revealed structured E. coli populations with high diversity between sites and individuals but low diversity within cattle hosts. Plasmid profiles, however, varied considerably within the same E. coli genotype. Both ecological and genetic factors affected plasmid distribution: plasmid profiles were affected by site, E. coli diversity, E. coli genotype and the presence of other large plasmids. Notably 3/26 E. coli serotypes accounted for half the observed plasmid-free isolates indicating that within species variation can substantially affect carriage of the major conjugative plasmids. The observed population structure suggest that most of the opportunities for within species plasmid transfer occur between different individuals of the same genotype and support recent experimental work indicating that plasmid-host coevolution, and epistatic interactions on fitness costs are likely to be important in determining occupancy. © 2016 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Characterization of ApB73, a virulence factor important for colonization of Zea mays by the smut Ustilago maydis

PubMed Central

Stirnberg, Alexandra

2016-01-01

Summary The biotrophic fungus Ustilago maydis, the causal agent of corn smut disease, uses numerous small secreted effector proteins to suppress plant defence responses and reshape the host metabolism. However, the role of specific effectors remains poorly understood. Here, we describe the identification of ApB73 (Apathogenic in B73), an as yet uncharacterized protein essential for the successful colonization of maize by U. maydis. We show that apB73 is transcriptionally induced during the biotrophic stages of the fungal life cycle. The deletion of the apB73 gene results in cultivar‐specific loss of gall formation in the host. The ApB73 protein is conserved among closely related smut fungi. However, using virulence assays, we show that only the orthologue of the maize‐infecting head smut Sporisorium reilianum can complement the mutant phenotype of U. maydis. Although microscopy shows that ApB73 is secreted into the biotrophic interface, it seems to remain associated with fungal cell wall components or the fungal plasma membrane. Taken together, the results show that ApB73 is a conserved and important virulence factor of U. maydis that localizes to the interface between the pathogen and its host Zea mays. PMID:27279632

ECOLOGICAL DETERMINANTS OF AVIAN INFLUENZA VIRUS, WEST NILE VIRUS, AND AVIAN PARAMYXOVIRUS INFECTION AND ANTIBODY STATUS IN BLUE-WINGED TEAL (ANAS DISCORS) IN THE CANADIAN PRAIRIES.

PubMed

Nallar, Rodolfo; Papp, Zsuzsanna; Leighton, Frederick A; Epp, Tasha; Pasick, John; Berhane, Yohannes; Lindsay, Robbin; Soos, Catherine

2016-01-01

The Canadian prairies are one of the most important breeding and staging areas for migratory waterfowl in North America. Hundreds of thousands of waterfowl of numerous species from multiple flyways converge in and disperse from this region annually; therefore this region may be a key area for potential intra- and interspecific spread of infectious pathogens among migratory waterfowl in the Americas. Using Blue-winged Teal (Anas discors, BWTE), which have the most extensive migratory range among waterfowl species, we investigated ecologic risk factors for infection and antibody status to avian influenza virus (AIV), West Nile virus (WNV), and avian paramyxovirus-1 (APMV-1) in the three prairie provinces (Alberta, Saskatchewan, and Manitoba) prior to fall migration. We used generalized linear models to examine infection or evidence of exposure in relation to host (age, sex, body condition, exposure to other infections), spatiotemporal (year, province), population-level (local population densities of BWTE, total waterfowl densities), and environmental (local pond densities) factors. The probability of AIV infection in BWTE was associated with host factors (e.g., age and antibody status), population-level factors (e.g., local BWTE population density), and year. An interaction between age and AIV antibody status showed that hatch year birds with antibodies to AIV were more likely to be infected, suggesting an antibody response to an active infection. Infection with AIV was positively associated with local BWTE density, supporting the hypothesis of density-dependent transmission. The presence of antibodies to WNV and APMV-1 was positively associated with age and varied among years. Furthermore, the probability of being WNV antibody positive was positively associated with pond density rather than host population density, likely because ponds provide suitable breeding habitat for mosquitoes, the primary vectors for transmission. Our findings highlight the importance of spatiotemporal, environmental, and host factors at the individual and population levels, all of which may influence dynamics of these and other viruses in wild waterfowl populations.

Huanglongbing: An overview of a complex pathosystem ravaging the world's citrus.

PubMed

da Graça, John V; Douhan, Greg W; Halbert, Susan E; Keremane, Manjunath L; Lee, Richard F; Vidalakis, Georgios; Zhao, Hongwei

2016-04-01

Citrus huanglongbing (HLB) has become a major disease and limiting factor of production in citrus areas that have become infected. The destruction to the affected citrus industries has resulted in a tremendous increase to support research that in return has resulted in significant information on both applied and basic knowledge concerning this important disease to the global citrus industry. Recent research indicates the relationship between citrus and the causal agent of HLB is shaped by multiple elements, in which host defense responses may also play an important role. This review is intended to provide an overview of the importance of HLB to a wider audience of plant biologists. Recent advances on host-pathogen interactions, population genetics and vectoring of the causal agent are discussed. © 2015 Institute of Botany, Chinese Academy of Sciences.

Morphology heterogeneity within a Campylobacter jejuni helical population

USDA-ARS?s Scientific Manuscript database

Campylobacter jejuni helical shape is an important factor in colonization and host interactions with straight mutants having altered biological properties. Passage on calcofluor white (CFW) led to the selection of C. jejuni 81-176 isolates with changes in morphology resulting in either a straight mo...

Capsular Polysaccharide Interferes With Biofilm Formation by Pasteurella Multocida Serogroup A

USDA-ARS?s Scientific Manuscript database

Pasteurella multocida is an important multihost animal and zoonotic pathogen that is capable of causing respiratory and multisystemic diseases, bacteremia,and bite wound infections. The glycosaminoglycan capsule of P. multocida is an essential virulence factor that protects the bacterium from host d...

Facilitating Lewin's change model with collaborative evaluation in promoting evidence based practices of health professionals.

PubMed

Manchester, Julianne; Gray-Miceli, Deanna L; Metcalf, Judith A; Paolini, Charlotte A; Napier, Anne H; Coogle, Constance L; Owens, Myra G

2014-12-01

Evidence based practices (EBPs) in clinical settings interact with and adapt to host organizational characteristics. The contextual factors themselves, surrounding health professions' practices, also adapt as practices become sustained. The authors assert the need for better planning models toward these contextual factors, the influence of which undergird a well-documented science to practice gap in literature on EBPs. The mechanism for EBP planners to anticipate contextual effects as programs Unfreeze their host settings, create Movement, and become Refrozen (Lewin, 1951) is present in Lewin's 3-step change model. Planning for contextual change appears equally important as planning for the actual practice outcomes among providers and patients. Two case studies from a Geriatric Education Center network will illustrate the synthesis of Lewin's three steps with collaborative evaluation principles. The use of the model may become an important tool for continuing education evaluators or organizations beginning a journey toward EBP demonstration projects in clinical settings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Host and parasite morphology influence congruence between host and parasite phylogenies.

PubMed

Sweet, Andrew D; Bush, Sarah E; Gustafsson, Daniel R; Allen, Julie M; DiBlasi, Emily; Skeen, Heather R; Weckstein, Jason D; Johnson, Kevin P

2018-03-23

Comparisons of host and parasite phylogenies often show varying degrees of phylogenetic congruence. However, few studies have rigorously explored the factors driving this variation. Multiple factors such as host or parasite morphology may govern the degree of phylogenetic congruence. An ideal analysis for understanding the factors correlated with congruence would focus on a diverse host-parasite system for increased variation and statistical power. In this study, we focused on the Brueelia-complex, a diverse and widespread group of feather lice that primarily parasitise songbirds. We generated a molecular phylogeny of the lice and compared this tree with a phylogeny of their avian hosts. We also tested for the contribution of each host-parasite association to the overall congruence. The two trees overall were significantly congruent, but the contribution of individual associations to this congruence varied. To understand this variation, we developed a novel approach to test whether host, parasite or biogeographic factors were statistically associated with patterns of congruence. Both host plumage dimorphism and parasite ecomorphology were associated with patterns of congruence, whereas host body size, other plumage traits and biogeography were not. Our results lay the framework for future studies to further elucidate how these factors influence the process of host-parasite coevolution. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Transcriptomic analysis reveals Toxoplasma gondii strain-specific differences in host cell response to dense granule protein GRA15.

PubMed

Liu, Qing; Gao, Wen-Wei; Elsheikha, Hany M; He, Jun-Jun; Li, Fa-Cai; Yang, Wen-Bin; Zhu, Xing-Quan

2018-06-19

Growth and replication of the protozoan parasite Toxoplasma gondii within host cell entail the production of several effector proteins, which the parasite exploits for counteracting the host's immune response. Despite considerable research to define the host signaling pathways manipulated by T. gondii and their effectors, there has been limited progress into understanding how individual members of the dense granule proteins (GRAs) modulate gene expression within host cells. The aim of this study was to evaluate whether T. gondii GRA15 protein plays any role in regulating host gene expression. Baby hamster kidney cells (BHK-21) were transfected with plasmids encoding GRA15 genes of either type I GT1 strain (GRA15 I ) or type II PRU strain (GRA15 II ). Gene expression patterns of transfected and nontransfected BHK-21 cells were investigated using RNA-sequencing analysis. GRA15 I and GRA15 II induced both known and novel transcriptional changes in the transfected BHK-21 cells compared with nontransfected cells. Pathway analysis revealed that GRA15 II was mainly involved in the regulation of tumor necrosis factor (TNF), NF-κB, HTLV-I infection, and NOD-like receptor signaling pathways. GRA15 I preferentially influenced the synthesis of unsaturated fatty acids in host cells. Our findings support the hypothesis that certain functions of GRA15 protein are strain dependent and that GRA15 modulates the expression of signaling pathways and genes with important roles in T. gondii pathophysiology. A greater understanding of host signaling pathways influenced by T. gondii effectors would allow the development of more efficient anti-T. gondii therapeutic schemes, capitalizing on disrupting parasite virulence factors to advance the treatment of toxoplasmosis.

Adherence of Candida sp. to host tissues and cells as one of its pathogenicity features.

PubMed

Modrzewska, Barbara; Kurnatowski, Piotr

2015-01-01

The ability of Candida sp. cells to adhere to the mucosal surfaces of various host organs as well as synthetic materials is an important pathogenicity feature of those fungi which contributes to the development of infection. This property varies depending on the species of the fungus and is the greatest for C. albicans. The process of adhesion depends on plenty of factors related to the fungal and host cells as well as environmental conditions. The main adhesins present on the fungal cell wall are: Als, Epa, Hwp1, but also Eap1, Sun41, Csh1 and probably Hyr1; for adhesion significant are also secreted aspartyl proteases Sap. Various researchers specify a range of genes which contribute to adhesion, such as: CZF1, EFG1, TUP1, TPK1, TPK2, HGC1, RAS1, RIM101, VPS11, ECM1, CKA2, BCR1, BUD2, RSR1, IRS4, CHS2, SCS7, UBI4, UME6, TEC1 and GAT2. Influence for adherence have also heat shock proteins Hsp70, Mediator Middle domain subunit Med31 and morphological transition. Among factors affecting adhesion related to host cells it is necessary to mention fibronectins and integrins (receptors for Candida sp. adhesins), type of epithelial cells, their morphology and differentiation phase. To a lesser degree influence on adhesion have non-specific factors and environmental conditions.

A furoviral replicase recruits host HSP70 to membranes for viral RNA replication

PubMed Central

Yang, Jian; Zhang, Fen; Cai, Nian-Jun; Wu, Ne; Chen, Xuan; Li, Jing; Meng, Xiang-Feng; Zhu, Tong-Quan; Chen, Jian-Ping; Zhang, Heng-Mu

2017-01-01

Many host factors have been identified to be involved in viral infection. However, although furoviruses cause important diseases of cereals worldwide, no host factors have yet been identified that interact with furoviral genes or participate in the viral infection cycle. In this study, both TaHSP70 and NbHSP70 were up-regulated in Chinese wheat mosaic furovirus (CWMV)-infected plants. Their overexpression and inhibition were correlated with the accumulation of viral genomic RNAs, suggesting that the HSP70 genes could be necessary for CWMV infection. The subcellular distributions of TaHSP70 and NbHSP70 were significantly affected by CWMV infection or by infiltration of RNA1 alone. Further assays showed that the viral replicase encoded by CWMV RNA1 interacts with both TaHSP70 and NbHSP70 in vivo and vitro and that its region aa167–333 was responsible for the interaction. Subcellular assays showed that the viral replicase could recruit both TaHSP70 and NbHSP70 from the cytoplasm or nucleus to the granular aggregations or inclusion-like structures on the intracellular membrane system, suggesting that both HSP70s may be recruited into the viral replication complex (VRC) to promote furoviral replication. This is the first host factor identified to be involved in furoviral infection, which extends the list and functional scope of HSP70 chaperones. PMID:28367995

Bacterial flagellin—a potent immunomodulatory agent

PubMed Central

Hajam, Irshad A; Dar, Pervaiz A; Shahnawaz, Imam; Jaume, Juan Carlos; Lee, John Hwa

2017-01-01

Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility. Traditionally, flagellin was viewed as a virulence factor that contributes to the adhesion and invasion of host cells, but now it has emerged as a potent immune activator, shaping both the innate and adaptive arms of immunity during microbial infections. In this review, we summarize our understanding of bacterial flagellin and host immune system interactions and the role flagellin as an adjuvant, anti-tumor and radioprotective agent, and we address important areas of future research interests. PMID:28860663

Host partitioning by parasites in an intertidal crustacean community.

PubMed

Koehler, Anson V; Poulin, Robert

2010-10-01

Patterns of host use by parasites throughout a guild community of intermediate hosts can depend on several biological and ecological factors, including physiology, morphology, immunology, and behavior. We looked at parasite transmission in the intertidal crustacean community of Lower Portobello Bay, Dunedin, New Zealand, with the intent of: (1) mapping the flow of parasites throughout the major crustacean species, (2) identifying hosts that play the most important transmission role for each parasite, and (3) assessing the impact of parasitism on host populations. The most prevalent parasites found in 14 species of crustaceans (635 specimens) examined were the trematodes Maritrema novaezealandensis and Microphallus sp., the acanthocephalans Profilicollis spp., the nematode Ascarophis sp., and an acuariid nematode. Decapods were compatible hosts for M. novaezealandensis, while other crustaceans demonstrated lower host suitability as shown by high levels of melanized and immature parasite stages. Carapace thickness, gill morphology, and breathing style may contribute to the differential infection success of M. novaezealandensis and Microphallus sp. in the decapod species. Parasite-induced host mortality appears likely with M. novaezealandensis in the crabs Austrohelice crassa, Halicarcinus varius, Hemigrapsus sexdentatus, and Macrophthalmus hirtipes, and also with Microphallus sp. in A. crassa. Overall, the different parasite species make different use of available crustacean intermediate hosts and possibly contribute to intertidal community structure.

Day-to-Day Population Movement and the Management of Dengue Epidemics.

PubMed

Falcón-Lezama, Jorge A; Martínez-Vega, Ruth A; Kuri-Morales, Pablo A; Ramos-Castañeda, José; Adams, Ben

2016-10-01

Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People's day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector-host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector-host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector-host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector-host ratio and people's day-to-day movement patterns.

Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions*

PubMed Central

Memišević, Vesna; Zavaljevski, Nela; Pieper, Rembert; Rajagopala, Seesandra V.; Kwon, Keehwan; Townsend, Katherine; Yu, Chenggang; Yu, Xueping; DeShazer, David; Reifman, Jaques; Wallqvist, Anders

2013-01-01

Burkholderia mallei is an infectious intracellular pathogen whose virulence and resistance to antibiotics makes it a potential bioterrorism agent. Given its genetic origin as a commensal soil organism, it is equipped with an extensive and varied set of adapted mechanisms to cope with and modulate host-cell environments. One essential virulence mechanism constitutes the specialized secretion systems that are designed to penetrate host-cell membranes and insert pathogen proteins directly into the host cell's cytosol. However, the secretion systems' proteins and, in particular, their host targets are largely uncharacterized. Here, we used a combined in silico, in vitro, and in vivo approach to identify B. mallei proteins required for pathogenicity. We used bioinformatics tools, including orthology detection and ab initio predictions of secretion system proteins, as well as published experimental Burkholderia data to initially select a small number of proteins as putative virulence factors. We then used yeast two-hybrid assays against normalized whole human and whole murine proteome libraries to detect and identify interactions among each of these bacterial proteins and host proteins. Analysis of such interactions provided both verification of known virulence factors and identification of three new putative virulence proteins. We successfully created insertion mutants for each of these three proteins using the virulent B. mallei ATCC 23344 strain. We exposed BALB/c mice to mutant strains and the wild-type strain in an aerosol challenge model using lethal B. mallei doses. In each set of experiments, mice exposed to mutant strains survived for the 21-day duration of the experiment, whereas mice exposed to the wild-type strain rapidly died. Given their in vivo role in pathogenicity, and based on the yeast two-hybrid interaction data, these results point to the importance of these pathogen proteins in modulating host ubiquitination pathways, phagosomal escape, and actin-cytoskeleton rearrangement processes. PMID:23800426

A murine host cell factor required for nicking of the dimer bridge of MVM recognizes two CG nucleotides displaced by 10 basepairs.

PubMed

Liu, Q; Astell, C R

1996-10-01

During replication of the minute virus of mice (MVM) genome, a dimer replicative form (RF) intermediate is resolved into two monomer RF molecules in such a way as to retain a unique sequence within the left hand hairpin terminus of the viral genome. Although the proposed mechanism for resolution of the dimer RF remains uncertain, it likely involves site-specific nicking of the dimer bridge. The RF contains two double-stranded copies of the viral genome joined by the extended 3' hairpin. Minor sequence asymmetries within the 3' hairpin allow the two halves of the dimer bridge to be distinguished. The A half contains the sequence [sequence: see text], whereas the B half contains the sequence [sequence: see text]. Using an in vitro assay, we show that only the B half of the MVM dimer bridge is nicked site-specifically when incubated with crude NS-1 protein (expressed in insect cells) and mouse LA9 cellular extract. When highly purified NS-1, the major nonstructural protein of MVM, is used in this nicking reaction, there is an absolute requirement for the LA9 cellular extract, suggesting a cellular factor (or factors) is (are) required. A series of mutations were created in the putative host factor binding region (HFBR) on the B half of the MVM dimer bridge adjacent to the NS-1 binding site. Nicking assays of these B half mutants showed that two CG motifs displaced by 10 nucleotides are important for nicking. Gel mobility shift assays demonstrated that a host factor(s) can bind to the HFBR of the B half of the dimer bridge and efficient binding depends on the presence of both CG motifs. Competitor DNA containing the wild-type HFBR sequence is able to specifically inhibit nicking of the B half, indicating that the host factor(s) bound to the HFBR is(are) essential for site-specific nicking to occur.

Nuclear factor-kappaB bioluminescence imaging-guided transcriptomic analysis for the assessment of host-biomaterial interaction in vivo.

PubMed

Hsiang, Chien-Yun; Chen, Yueh-Sheng; Ho, Tin-Yun

2009-06-01

Establishment of a comprehensive platform for the assessment of host-biomaterial interaction in vivo is an important issue. Nuclear factor-kappaB (NF-kappaB) is an inducible transcription factor that is activated by numerous stimuli. Therefore, NF-kappaB-dependent luminescent signal in transgenic mice carrying the luciferase genes was used as the guide to monitor the biomaterials-affected organs, and transcriptomic analysis was further applied to evaluate the complex host responses in affected organs in this study. In vivo imaging showed that genipin-cross-linked gelatin conduit (GGC) implantation evoked the strong NF-kappaB activity at 6h in the implanted region, and transcriptomic analysis showed that the expressions of interleukin-6 (IL-6), IL-24, and IL-1 family were up-regulated. A strong luminescent signal was observed in spleen on 14 d, suggesting that GGC implantation might elicit the biological events in spleen. Transcriptomic analysis of spleen showed that 13 Kyoto Encyclopedia of Genes and Genomes pathways belonging to cell cycles, immune responses, and metabolism were significantly altered by GGC implants. Connectivity Map analysis suggested that the gene signatures of GGC were similar to those of compounds that affect lipid or glucose metabolism. GeneSetTest analysis further showed that host responses to GGC implants might be related to diseases states, especially the metabolic and cardiovascular diseases. In conclusion, our data provided a concept of molecular imaging-guided transcriptomic platform for the evaluation and the prediction of host-biomaterial interaction in vivo.

Homologous Recombination between Genetically Divergent Campylobacter fetus Lineages Supports Host-Associated Speciation

PubMed Central

Duim, Birgitta; van der Graaf-van Bloois, Linda; Wagenaar, Jaap A; Zomer, Aldert L

2018-01-01

Abstract Homologous recombination is a major driver of bacterial speciation. Genetic divergence and host association are important factors influencing homologous recombination. Here, we study these factors for Campylobacter fetus, which shows a distinct intraspecific host dichotomy. Campylobacter fetus subspecies fetus (Cff) and venerealis are associated with mammals, whereas C. fetus subsp. testudinum (Cft) is associated with reptiles. Recombination between these genetically divergent C. fetus lineages is extremely rare. Previously it was impossible to show whether this barrier to recombination was determined by the differential host preferences, by the genetic divergence between both lineages or by other factors influencing recombination, such as restriction-modification, CRISPR/Cas, and transformation systems. Fortuitously, a distinct C. fetus lineage (ST69) was found, which was highly related to mammal-associated C. fetus, yet isolated from a chelonian. The whole genome sequences of two C. fetus ST69 isolates were compared with those of mammal- and reptile-associated C. fetus strains for phylogenetic and recombination analysis. In total, 5.1–5.5% of the core genome of both ST69 isolates showed signs of recombination. Of the predicted recombination regions, 80.4% were most closely related to Cft, 14.3% to Cff, and 5.6% to C. iguaniorum. Recombination from C. fetus ST69 to Cft was also detected, but to a lesser extent and only in chelonian-associated Cft strains. This study shows that despite substantial genetic divergence no absolute barrier to homologous recombination exists between two distinct C. fetus lineages when occurring in the same host type, which provides valuable insights in bacterial speciation and evolution. PMID:29608720

Microbiota-gut-brain axis: Interaction of gut microbes and their metabolites with host epithelial barriers.

PubMed

Bhattarai, Y

2018-06-01

The gastrointestinal barrier and the blood brain barrier represent an important line of defense to protect the underlying structures against harmful external stimuli. These host barriers are composed of epithelial and endothelial cells interconnected by tight junction proteins along with several other supporting structures. Disruption in host barrier structures has therefore been implicated in various diseases of the gastrointestinal tract and the central nervous system. While there are several factors that influence host barrier, recently there is an increasing appreciation of the role of gut microbiota and their metabolites in regulating barrier integrity. In the current issue of Neurogastroenterology and Motility, Marungruang et al. describe the effect of gastrointestinal barrier maturation on gut microbiota and the blood brain barrier adding to the growing evidence of microbiota-barrier interactions. In this mini-review I will discuss the effect of gut microbiota on host epithelial barriers and its implications for diseases associated with disrupted gut-brain axis. © 2018 John Wiley & Sons Ltd.

Immunology of Bats and Their Viruses: Challenges and Opportunities

PubMed Central

Schountz, Tony

2014-01-01

Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock. PMID:25494448

Immunology of bats and their viruses: challenges and opportunities.

PubMed

Schountz, Tony

2014-12-01

Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.

Novel bioassay demonstrates attraction of the white potato cyst nematode Globodera pallida (Stone) to non-volatile and volatile host plant cues.

PubMed

Farnier, Kevin; Bengtsson, Marie; Becher, Paul G; Witzell, Johanna; Witzgall, Peter; Manduríc, Sanja

2012-06-01

Potato cyst nematodes (PCNs) are a major pest of solanaceous crops such as potatoes, tomatoes, and eggplants and have been widely studied over the last 30 years, with the majority of earlier studies focusing on the identification of natural hatching factors. As a novel approach, we focused instead on chemicals involved in nematode orientation towards its host plant. A new dual choice sand bioassay was designed to study nematode responses to potato root exudates (PRE). This bioassay, conducted together with a traditional hatching bioassay, showed that biologically active compounds that induce both hatching and attraction of PCNs can be collected by water extraction of incised potato roots. Furthermore, our results demonstrated that PCN also were attracted by potato root volatiles. Further work is needed to fully understand how PCNs use host plant chemical cues to orientate towards hosts. Nevertheless, the simple attraction assay used in this study provides an important tool for the identification of host-emitted attractants.

Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells

PubMed Central

Hadis, Mohammed; Alderwick, Luke

2017-01-01

Outer membrane vesicles are nano-sized microvesicles shed from the outer membrane of Gram-negative bacteria and play important roles in immune priming and disease pathogenesis. However, our current mechanistic understanding of vesicle-host cell interactions is limited by a lack of methods to study the rapid kinetics of vesicle entry and cargo delivery to host cells. Here, we describe a highly sensitive method to study the kinetics of vesicle entry into host cells in real-time using a genetically encoded, vesicle-targeted probe. We found that the route of vesicular uptake, and thus entry kinetics and efficiency, are shaped by bacterial cell wall composition. The presence of lipopolysaccharide O antigen enables vesicles to bypass clathrin-mediated endocytosis, which enhances both their entry rate and efficiency into host cells. Collectively, our findings highlight the composition of the bacterial cell wall as a major determinant of secretion-independent delivery of virulence factors during Gram-negative infections. PMID:29186191

Serine/Arginine-rich Splicing Factor 2 Modulates Herpes Simplex Virus Type 1 Replication via Regulating Viral Gene Transcriptional Activity and Pre-mRNA Splicing.

PubMed

Wang, Ziqiang; Liu, Qing; Lu, Jinhua; Fan, Ping; Xie, Weidong; Qiu, Wei; Wang, Fan; Hu, Guangnan; Zhang, Yaou

2016-12-16

Once it enters the host cell, herpes simplex virus type 1 (HSV-1) recruits a series of host cell factors to facilitate its life cycle. Here, we demonstrate that serine/arginine-rich splicing factor 2 (SRSF2), which is an important component of the splicing speckle, mediates HSV-1 replication by regulating viral gene expression at the transcriptional and posttranscriptional levels. Our results indicate that SRSF2 functions as a transcriptional activator by directly binding to infected cell polypeptide 0 (ICP0), infected cell polypeptide 27 (ICP27), and thymidine kinase promoters. Moreover, SRSF2 participates in ICP0 pre-mRNA splicing by recognizing binding sites in ICP0 exon 3. These findings provide insight into the functions of SRSF2 in HSV-1 replication and gene expression. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Spontaneous Elimination of Hepatitis C Virus Infection.

PubMed

Janiak, Maciej; Caraballo Cortes, Kamila; Demkow, Urszula; Radkowski, Marek

2018-01-01

Hepatitis C virus (HCV) is the etiological agent of chronic hepatitis C and a major cause of liver cirrhosis and hepatocellular carcinoma. Only a minority of infected individuals can clear the virus spontaneously. The knowledge of the determinants of virus clearance would allow the development of effective methods preventing its further spread and optimizing treatment regimens. Viral factors associated with spontaneous virus clearance in the acute phase of infection, such as HCV genotype, virus heterogeneity, and the impact of viral proteins on the immune system have been characterized. Likewise, host genetic markers, such as the interleukin genotypes, HLA alleles, and factors affecting the T lymphocyte response appear to play an important role. Studies have revealed that natural clearance of HCV infection in the chronic phase is rare and its mechanisms are not well understood. In this review, we present the state-of-the art knowledge on the viral and host factors affecting the spontaneous elimination of HCV infection.

Macronutrients mediate the functional relationship between Drosophila and Wolbachia

PubMed Central

Ponton, Fleur; Wilson, Kenneth; Holmes, Andrew; Raubenheimer, David; Robinson, Katie L.; Simpson, Stephen J.

2015-01-01

Wolbachia are maternally inherited bacterial endosymbionts that naturally infect a diverse array of arthropods. They are primarily known for their manipulation of host reproductive biology, and recently, infections with Wolbachia have been proposed as a new strategy for controlling insect vectors and subsequent human-transmissible diseases. Yet, Wolbachia abundance has been shown to vary greatly between individuals and the magnitude of the effects of infection on host life-history traits and protection against infection is correlated to within-host Wolbachia abundance. It is therefore essential to better understand the factors that modulate Wolbachia abundance and effects on host fitness. Nutrition is known to be one of the most important mediators of host–symbiont interactions. Here, we used nutritional geometry to quantify the role of macronutrients on insect–Wolbachia relationships in Drosophila melanogaster. Our results show fundamental interactions between diet composition, host diet selection, Wolbachia abundance and effects on host lifespan and fecundity. The results and methods described here open a new avenue in the study of insect–Wolbachia relationships and are of general interest to numerous research disciplines, ranging from nutrition and life-history theory to public health. PMID:25520356

Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

PubMed

Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

2015-10-28

Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

Targeting the complex interactions between microbiota, host epithelial and immune cells in inflammatory bowel disease.

PubMed

Hirata, Yoshihiro; Ihara, Sozaburo; Koike, Kazuhiko

2016-11-01

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder that includes two distinct disease categories: ulcerative colitis and Crohn's disease. Epidemiological, genetic, and experimental studies have revealed many important aspects of IBD. Genetic susceptibility, inappropriate immune responses, environmental changes, and intestinal microbiota are all associated with the development of IBD. However, the exact mechanisms of the disease and the interactions among these pathogenic factors are largely unknown. Here we introduce recent findings from experimental colitis models that investigated the interactions between host genetic susceptibility and gut microbiota. In addition, we discuss new strategies for the treatment of IBD, focusing on the complex interactions between microbiota and host epithelial and immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unraveling the environmental and genetic interactions in atherosclerosis: Central role of the gut microbiota.

PubMed

Org, Elin; Mehrabian, Margarete; Lusis, Aldons J

2015-08-01

Recent studies have convincingly linked gut microbiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gut microbiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gut microbiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.

PubMed

Shaw, Liam; Ribeiro, Andre L R; Levine, Adam P; Pontikos, Nikolas; Balloux, Francois; Segal, Anthony W; Roberts, Adam P; Smith, Andrew M

2017-09-12

The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years. Copyright © 2017 Shaw et al.

The role of hyperparasitism in microbial pathogen ecology and evolution.

PubMed

Parratt, Steven R; Laine, Anna-Liisa

2016-08-01

Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and natural ecosystems. Most pathogens are likely to host parasites of their own, that is, hyperparasites, but how nested chains of parasites impact on disease dynamics is grossly neglected in the ecological and evolutionary literature. In this minireview we argue that the diversity and dynamics of micro-hyperparasites are an important component of natural host-pathogen systems. We use the current literature from a handful of key systems to show that observed patterns of pathogen virulence and disease dynamics may well be influenced by hyperparasites. Exploring these factors will shed light on many aspects of microbial ecology and disease biology, including resistance-virulence evolution, apparent competition, epidemiology and ecosystem stability. Considering the importance of hyperparasites in natural populations will have applied consequences for the field of biological control and therapeutic science, where hyperparastism is employed as a control mechanism but not necessarily ecologically understood.

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner

PubMed Central

Hughes, K. R.; Harnisch, L. C.; Alcon-Giner, C.; Mitra, S.; Wright, C. J.; Ketskemety, J.

2017-01-01

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes. PMID:28123052

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.

PubMed

Hughes, K R; Harnisch, L C; Alcon-Giner, C; Mitra, S; Wright, C J; Ketskemety, J; van Sinderen, D; Watson, A J M; Hall, L J

2017-01-01

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi-a process termed 'cell shedding'. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes. © 2017 The Authors.

Molecular epidemiology of Escherichia coli mediated urinary tract infections.

PubMed

Zhang, Lixin; Foxman, Betsy

2003-01-01

Urinary tract infection (UTI) is one of the most frequently acquired bacterial infections and Escherichia coli accounts for as many as 90% of all UTIs seen among ambulatory populations. Risk factors for UTIs include host behaviors, host characteristics and bacterial characteristics. Sexual activity and contraceptive method are the strongest determinant of a symptomatic UTI episode. The characteristics of cell receptors, anatomical differences and genetic predisposition in the host may be important determinants of increased risk for recurrent infections. Uropathogenic E. coli have special characteristics causing urovirulence. They most likely belong to phylogenic lineage B2. They usually possess specific adhesins such as P, S or Dr to facilitate their colonization in the urinary tract, and toxins such as hemolysin and cytotoxic necrotizing factor 1 to provoke inflammatory response that possibly are responsible for the development of UTI symptoms. Interestingly, virulence genes in uropathogenic E. coli are often co-located on pathogenicity islands. Currently, however, none of the known virulence genes or set of genes can clearly define the prototypic uropathogenic E. coli. Additional studies are needed to identify factors that promote uropathogen transmission and persistent colonization, and to investigate potential different modes of pathogenesis by E. coli strains with different compositions of virulence genes.

Factors associated with parasite dominance in fishes from Brazil.

PubMed

Amarante, Cristina Fernandes do; Tassinari, Wagner de Souza; Luque, Jose Luis; Pereira, Maria Julia Salim

2016-06-14

The present study used regression models to evaluate the existence of factors that may influence the numerical parasite dominance with an epidemiological approximation. A database including 3,746 fish specimens and their respective parasites were used to evaluate the relationship between parasite dominance and biotic characteristics inherent to the studied hosts and the parasite taxa. Multivariate, classical, and mixed effects linear regression models were fitted. The calculations were performed using R software (95% CI). In the fitting of the classical multiple linear regression model, freshwater and planktivorous fish species and body length, as well as the species of the taxa Trematoda, Monogenea, and Hirudinea, were associated with parasite dominance. However, the fitting of the mixed effects model showed that the body length of the host and the species of the taxa Nematoda, Trematoda, Monogenea, Hirudinea, and Crustacea were significantly associated with parasite dominance. Studies that consider specific biological aspects of the hosts and parasites should expand the knowledge regarding factors that influence the numerical dominance of fish in Brazil. The use of a mixed model shows, once again, the importance of the appropriate use of a model correlated with the characteristics of the data to obtain consistent results.

Landscape and host plant effects on reproduction by a mobile, polyphagous, multivoltine arthropod herbivore

USDA-ARS?s Scientific Manuscript database

Landscape factors can significantly influence arthropod natural enemy and herbivore pest populations. The economically important brown stink bug, Euschistus servus, is a native mobile, polyphagous and multivoltine pest of many crops in southeastern USA and understanding the relative influence of loc...

Human susceptibility to legionnaires' disease.

PubMed

Berrington, William R; Hawn, Thomas R

2013-01-01

Legionella pneumophila is a facultative intracellular pathogen that is an important cause of pneumonia. Although host factors that may predispose to acquisition of Legionnaire's Disease (LD) include comorbid illnesses (e.g., diabetes, chronic lung disease), age, male sex, and smoking, many individuals have no identifiable risk factors. Some studies suggest that genetic factors may enhance susceptibility to LD. In this chapter we discuss current techniques and scientific methods to identify genetic susceptibility factors. These genetic studies provide insight into the human immune response to intracellular pathogens and may improve strategies for treatment and vaccine development.

Gut microbiota in autoimmunity: potential for clinical applications.

PubMed

Kim, Donghyun; Yoo, Seung-Ah; Kim, Wan-Uk

2016-11-01

Microbial habitation in the human body begins immediately after birth, and adults are colonized by microbes outnumbering human cells by a factor of ten. Especially, intestinal track is a living space for diverse microbial species that have coevolved symbiotically. A principal function of the gut microbiota is to protect the host from harmful bacteria and to provide benefits for the host through several mechanisms, including direct competition for limited nutrients, training of host immune systems to recognize specifically foreign materials and conversion of otherwise indigestible food into energy and absorbable nutrients. Therefore, gut dysbiosis, a bacterial imbalance state, is related with the pathogenesis of various host diseases including autoimmune diseases. In the current review, we highlight the importance of gut microbiota in the normal health and autoimmune diseases. We also discuss regulation of gut dysbiosis and future direction for potential clinical applications, including treatment and diagnostics of autoimmune diseases.

Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events

PubMed Central

Potrykus, Joanna; Stead, David; MacCallum, Donna M.; Urgast, Dagmar S.; Raab, Andrea; van Rooijen, Nico; Feldmann, Jörg; Brown, Alistair J. P.

2013-01-01

Nutritional immunity – the withholding of nutrients by the host – has long been recognised as an important factor that shapes bacterial-host interactions. However, the dynamics of nutrient availability within local host niches during fungal infection are poorly defined. We have combined laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS), MALDI imaging and immunohistochemistry with microtranscriptomics to examine iron homeostasis in the host and pathogen in the murine model of systemic candidiasis. Dramatic changes in the renal iron landscape occur during disease progression. The infection perturbs global iron homeostasis in the host leading to iron accumulation in the renal medulla. Paradoxically, this is accompanied by nutritional immunity in the renal cortex as iron exclusion zones emerge locally around fungal lesions. These exclusion zones correlate with immune infiltrates and haem oxygenase 1-expressing host cells. This local nutritional immunity decreases iron availability, leading to a switch in iron acquisition mechanisms within mature fungal lesions, as revealed by laser capture microdissection and qRT-PCR analyses. Therefore, a complex interplay of systemic and local events influences iron homeostasis and pathogen-host dynamics during disease progression. PMID:24146619

Regulation of the Host Antiviral State by Intercellular Communications

PubMed Central

Assil, Sonia; Webster, Brian; Dreux, Marlène

2015-01-01

Viruses usually induce a profound remodeling of host cells, including the usurpation of host machinery to support their replication and production of virions to invade new cells. Nonetheless, recognition of viruses by the host often triggers innate immune signaling, preventing viral spread and modulating the function of immune cells. It conventionally occurs through production of antiviral factors and cytokines by infected cells. Virtually all viruses have evolved mechanisms to blunt such responses. Importantly, it is becoming increasingly recognized that infected cells also transmit signals to regulate innate immunity in uninfected neighboring cells. These alternative pathways are notably mediated by vesicular secretion of various virus- and host-derived products (miRNAs, RNAs, and proteins) and non-infectious viral particles. In this review, we focus on these newly-described modes of cell-to-cell communications and their impact on neighboring cell functions. The reception of these signals can have anti- and pro-viral impacts, as well as more complex effects in the host such as oncogenesis and inflammation. Therefore, these “broadcasting” functions, which might be tuned by an arms race involving selective evolution driven by either the host or the virus, constitute novel and original regulations of viral infection, either highly localized or systemic. PMID:26295405

Legionella: virulence factors and host response.

PubMed

Misch, Elizabeth Ann

2016-06-01

Legionella pneumophila is a facultative intracellular pathogen and an important cause of community-acquired and nosocomial pneumonia. This review focuses on the latest literature examining Legionella's virulence strategies and the mammalian host response. Recent studies identify novel virulence strategies used by L. pneumophila and new aspects of the host immune response to this pathogen. Legionella prevents acidification of the phagosome by recruiting Rab1, a host protein. Legionella also blocks a conserved endoplasmic reticulum stress response. To access iron from host stores, L. pneumophila upregulates more regions allowing vacuolar colocalization N. In response to Legionella, the host cell may activate caspase-1, caspase-11 (mice) or caspase-4 (humans). Caspase-3 and apoptosis are activated by a secreted, bacterial effector. Infected cells send signals to their uninfected neighbors, allowing the elaboration of inflammatory cytokines in trans. Antibody subclasses provide robust protection against Legionella. L. pneumophila is a significant human pathogen that lives in amoebae in the environment but may opportunistically infect the alveolar macrophage. To maintain its intracellular lifestyle, Legionella extracts essential iron from the cell, blocks inflammatory responses and manipulates trafficking to avoid fusion with the lysosome. The mammalian host has counter strategies, which include the release of proinflammatory cytokines, the activation of caspases and antibody-mediated immunity.

Clever birds are lousy: co-variation between avian innovation and the taxonomic richness of their amblyceran lice.

PubMed

Vas, Zoltán; Lefebvre, Louis; Johnson, Kevin P; Reiczigel, Jeno; Rózsa, Lajos

2011-10-01

Lice (Insecta: Phthiraptera) are ectoparasites that reduce host life expectancy and sexual attractiveness. Their taxonomic richness varies considerably among their hosts. Previous studies have already explored some important factors shaping louse diversity. An unexplored potential correlate of louse taxonomic richness is host behavioural flexibility. In this comparative study, we examine the relationship between louse generic richness, innovative capabilities (as a proxy for behavioural flexibility), and brain size while controlling for host species diversity, phylogeny, body size and research effort. Using data for 108 avian families, we found a highly significant positive relationship between host innovative capabilities and the taxonomic richness of amblyceran lice, but a lack of a similar relationship in ischnoceran lice. Host brain size had only a marginal impact on amblyceran diversity and no correlation with ischnoceran diversity. This suggests that the effect in Amblycera is not mediated by metabolic limitations due to the energetic costs of brain size and maintenance, rather directly caused by the ecological differences between hosts with differing cognitive capabilities. We propose four alternative and mutually non-exclusive hypotheses that may explain this phenomenon. Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

PubMed Central

Krishnan, Manoj N.; Garcia-Blanco, Mariano A.

2014-01-01

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. PMID:24517970

Targeting host factors to treat West Nile and dengue viral infections.

PubMed

Krishnan, Manoj N; Garcia-Blanco, Mariano A

2014-02-10

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

Host-derived viral transporter protein for nitrogen uptake in infected marine phytoplankton

PubMed Central

Chambouvet, Aurélie; Milner, David S.; Attah, Victoria; Terrado, Ramón; Lovejoy, Connie; Moreau, Hervé; Derelle, Évelyne; Richards, Thomas A.

2017-01-01

Phytoplankton community structure is shaped by both bottom–up factors, such as nutrient availability, and top–down processes, such as predation. Here we show that marine viruses can blur these distinctions, being able to amend how host cells acquire nutrients from their environment while also predating and lysing their algal hosts. Viral genomes often encode genes derived from their host. These genes may allow the virus to manipulate host metabolism to improve viral fitness. We identify in the genome of a phytoplankton virus, which infects the small green alga Ostreococcus tauri, a host-derived ammonium transporter. This gene is transcribed during infection and when expressed in yeast mutants the viral protein is located to the plasma membrane and rescues growth when cultured with ammonium as the sole nitrogen source. We also show that viral infection alters the nature of nitrogen compound uptake of host cells, by both increasing substrate affinity and allowing the host to access diverse nitrogen sources. This is important because the availability of nitrogen often limits phytoplankton growth. Collectively, these data show that a virus can acquire genes encoding nutrient transporters from a host genome and that expression of the viral gene can alter the nutrient uptake behavior of host cells. These results have implications for understanding how viruses manipulate the physiology and ecology of phytoplankton, influence marine nutrient cycles, and act as vectors for horizontal gene transfer. PMID:28827361

Microbiome structure influences infection by the parasite Crithidia bombi in bumble bees.

PubMed

Mockler, Blair K; Kwong, Waldan K; Moran, Nancy A; Koch, Hauke

2018-01-26

Recent declines in bumble bee populations are of great concern, and have prompted critical evaluations of the role of pathogen introductions and host resistance in bee health. One factor that may influence host resilience when facing infection is the gut microbiota. Previous experiments with Bombus terrestris , a European bumble bee, showed that the gut microbiota can protect against Crithidia bombi , a widespread trypanosomatid parasite of bumble bees. However, the particular characteristics of the microbiome responsible for this protective effect have thus far eluded identification. Using wild and commercially-sourced Bombus impatiens , an important North American pollinator, we conducted cross-wise microbiota transplants to naïve hosts of both backgrounds, and challenged them with Crithidia As with B. terrestris , we find that microbiota-dependent protection against Crithidia operates in B. impatiens Lower Crithidia infection loads were experimentally associated with high microbiome diversity, large gut bacterial populations, and the presence of Apibacter , Lactobacillus Firm-5, and Gilliamella in the gut community. These results indicate that even subtle differences between gut community structures can have a significant impact on the microbiome's ability to defend against parasite infections. Importance Many wild bumble bee populations are under threat by human activity, including through introductions of pathogens via commercially-raised bees. Recently, it was found that the bumble bee gut microbiota can help defend against a common parasite, Crithidia bombi , but the particular factors contributing to this protection are unknown. Using both wild and commercially-raised bees, we conduct microbiota transplants to show that microbiome diversity, total gut bacterial load, and the presence of certain core members of the microbiota may all impact bee susceptibility to Crithidia infection. Bee origin (genetic background) was also a factor. Finally, by examining this phenomenon in a previously uninvestigated bee species, our study demonstrates that microbiome-mediated resistance to Crithidia is conserved across multiple bumble bee species. These findings highlight how intricate interactions between hosts, microbiomes, and parasites can have wide-ranging consequences for the health of ecologically important species. Copyright © 2018 American Society for Microbiology.

Evasion of interferon responses by Ebola and Marburg viruses.

PubMed

Basler, Christopher F; Amarasinghe, Gaya K

2009-09-01

The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-alpha/beta production and inhibit signaling downstream of the IFN-alpha/beta and the IFN-gamma receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-epsilon and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-alpha/beta demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-alpha proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which these deadly viruses counteract the IFN system. It will be of interest to determine how these differences influence pathogenesis.

Molecular Neuro-Pathomechanism of Neurocysticercosis: How Host Genetic Factors Influence Disease Susceptibility.

PubMed

Arora, Naina; Tripathi, Shweta; Sao, Reshma; Mondal, Prosenjit; Mishra, Amit; Prasad, Amit

2018-02-01

Neurocysticercosis (NCC) is one of the most neglected tropical diseases among widely endemic neurological diseases. It is caused by cysticerci of Taenia solium. The clinical symptom for the outcome of infection and progression of disease is pleomorphic and its neuro-pathomechanism is still illusive. Identification of host genetic factors and their association with disease susceptibility is one of the most important areas of research towards personalized medicine in the era of omics. Several genes and their allelic variations had been identified to be associated with various neurological disorders; however, the information for parasitic diseases affecting the central nervous system is very limited. Both Th1 and Th2 arms of the immune system are reported to be active at different stages of T. solium infection in the brain. Recently, several papers had been published, where the role of host genetic makeup with NCC had been explored. Increased frequency of HLA-A28, HLA-B63, HLA-B58, TLR 4 Asp299Gly, sICAM-1 gene K469E, GSTM1, and GSTT1 were found to be associated with increased risk of NCC occurrence, while HLA-DQW2 and HLA-A11 were shown to be providing protection from disease. In this review, we have summarized these findings and analyzed the influence of host genetic polymorphism on the susceptibility/resistance of host to NCC.

Relative Effects of Temperature, Light, and Humidity on Clinging Behavior of Metacercariae-Infected Ants.

PubMed

Botnevik, C F; Malagocka, J; Jensen, A B; Fredensborg, B L

2016-10-01

The lancet fluke, Dicrocoelium dendriticum, is perhaps the best-known example of parasite manipulation of host behavior, which is manifested by a radically changed behavior that leaves infected ants attached to vegetation at times when transmission to an herbivore host is optimal. Despite the publicity surrounding this parasite, curiously little is known about factors inducing and maintaining behavioral changes in its ant intermediate host. This study examined the importance of 3 environmental factors on the clinging behavior of red wood ants, Formica polyctena , infected with D. dendriticum . This behavior, hypothesized to involve cramping of the mandibular muscles in a state of tetany, was observed in naturally infected F. polyctena under controlled temperature, light, and humidity conditions. We found that low temperature significantly stimulated and maintained tetany in infected ants while light, humidity, ant size, and infection intensity had no influence on this behavior. Under none of the experimental conditions did uninfected ants attach to vegetation, demonstrating that tetany was induced by D. dendriticum . Temperature likely has a direct impact on the initiation of clinging behavior, but it may also serve as a simple but reliable indicator of the encounter rate between infected ants and ruminant definitive hosts. In addition, temperature-sensitive behavior manipulation may protect infected ants from exposure to temperatures in the upper thermal range of the host.

Recognition, survival and persistence of Staphylococcus aureus in the model host Tenebrio molitor.

PubMed

Dorling, Jack; Moraes, Caroline; Rolff, Jens

2015-02-01

The degree of specificity of any given immune response to a parasite is governed by the complexity and variation of interactions between host and pathogen derived molecules. Here, we assess the extent to which recognition and immuno-resistance of cell wall mutants of the pathogen Staphylococcus aureus may contribute to establishment and maintenance of persistent infection in the model insect host, Tenebrio molitor. The cell surface of S. aureus is decorated with various molecules, including glycopolymers such as wall teichoic acid (WTA). WTA is covalently bound to peptidoglycan (PGN) and its absence has been associated with increased recognition of PGN by host receptors (PGRPs). WTA is also further modified by other molecules such as D-alanine (D-alanylation). Both the level of WTA expression and its D-alanylation were found to be important in the mediation of the host-parasite interaction in this model system. Specifically, WTA itself was seen to influence immune recognition, while D-alanylation of WTA was found to increase immuno-resistance and was associated with prolonged persistence of S. aureus in T. molitor. These results implicate WTA and its D-alanylation as important factors in the establishment and maintenance of persistent infection, affecting different critical junctions in the immune response; through potential evasion of recognition by PGRPs and resistance to humoral immune effectors during prolonged exposure to the immune system. This highlights a mechanism by which specificity in this host-parasite interaction may arise. Copyright © 2014 Elsevier Ltd. All rights reserved.

Targeting Drug-Sensitive and -Resistant Strains of Mycobacterium tuberculosis by Inhibition of Src Family Kinases Lowers Disease Burden and Pathology.

PubMed

Chandra, Pallavi; Rajmani, R S; Verma, Garima; Bhavesh, Neel Sarovar; Kumar, Dhiraj

2016-01-01

In view of emerging drug resistance among bacterial pathogens, including Mycobacterium tuberculosis, the development of novel therapeutic strategies is increasingly being sought. A recent paradigm in antituberculosis (anti-TB) drug development is to target the host molecules that are crucial for intracellular survival of the pathogen. We previously showed the importance of Src tyrosine kinases in mycobacterial pathogenesis. Here, we report that inhibition of Src significantly reduced survival of H37Rv as well as multidrug-resistant (MDR) and extremely drug-resistant (XDR) strains of M. tuberculosis in THP-1 macrophages. Src inhibition was also effective in controlling M. tuberculosis infection in guinea pigs. In guinea pigs, reduced M. tuberculosis burden due to Src inhibition also led to a marked decline in the disease pathology. In agreement with the theoretical framework of host-directed approaches against the pathogen, Src inhibition was equally effective against an XDR strain in controlling infection in guinea pigs. We propose that Src inhibitors could be developed into effective host-directed anti-TB drugs, which could be indiscriminately used against both drug-sensitive and drug-resistant strains of M. tuberculosis. IMPORTANCE The existing treatment regimen for tuberculosis (TB) suffers from deficiencies like high doses of antibiotics, long treatment duration, and inability to kill persistent populations in an efficient manner. Together, these contribute to the emergence of drug-resistant tuberculosis. Recently, several host factors were identified which help intracellular survival of Mycobacterium tuberculosis within the macrophage. These factors serve as attractive targets for developing alternate therapeutic strategies against M. tuberculosis. This strategy promises to be effective against drug-resistant strains. The approach also has potential to considerably lower the risk of emergence of new drug-resistant strains. We explored tyrosine kinase Src as a host factor exploited by virulent M. tuberculosis for intracellular survival. We show that Src inhibition can effectively control tuberculosis in infected guinea pigs. Moreover, Src inhibition ameliorated TB-associated pathology in guinea pigs. Thus, Src inhibitors have strong potential to be developed as possible anti-TB drugs.

Staphylococcus aureus Responds to the Central Metabolite Pyruvate To Regulate Virulence.

PubMed

Harper, Lamia; Balasubramanian, Divya; Ohneck, Elizabeth A; Sause, William E; Chapman, Jessica; Mejia-Sosa, Bryan; Lhakhang, Tenzin; Heguy, Adriana; Tsirigos, Aristotelis; Ueberheide, Beatrix; Boyd, Jeffrey M; Lun, Desmond S; Torres, Victor J

2018-01-23

Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for S. aureus pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux of S. aureus and enhances its pathogenicity. We demonstrate that pyruvate induces the production of virulence factors such as the pore-forming leucocidins and that this induction results in increased virulence of community-acquired methicillin-resistant S. aureus (CA-MRSA) clone USA300. Specifically, we show that an efficient "pyruvate response" requires the activation of S. aureus master regulators AgrAC and SaeRS as well as the ArlRS two-component system. Altogether, our report further establishes a strong relationship between metabolism and virulence and identifies pyruvate as a novel regulatory signal for the coordination of the S. aureus virulon through intricate regulatory networks. IMPORTANCE Delineation of the influence of host-derived small molecules on the makeup of human pathogens is a growing field in understanding host-pathogen interactions. S. aureus is a prominent pathogen that colonizes up to one-third of the human population and can cause serious infections that result in mortality in ~15% of cases. Here, we show that pyruvate, a key nutrient and central metabolite, causes global changes to the metabolic flux of S. aureus and activates regulatory networks that allow significant increases in the production of leucocidins. These and other virulence factors are critical for S. aureus to infect diverse host niches, initiate infections, and effectively subvert host immune responses. Understanding how environmental signals, particularly ones that are essential to and prominent in the human host, affect virulence will allow us to better understand pathogenicity and consider more-targeted approaches to tackling the current S. aureus epidemic. Copyright © 2018 Harper et al.

Dietary Factors Modulate Helicobacter-Associated Gastric Cancer in Rodent Models

PubMed Central

Fox, James G.; Wang, Timothy C.

2014-01-01

Since its discovery in 1982, the global importance of H. pylori-induced disease, particularly in developing countries, remains high. The use of rodent models particularly mice, and the unanticipated usefulness of the gerbil to study H. pylori pathogenesis have been used extensively to study the interactions of the host, the pathogen and the environmental conditions influencing the outcome of persistent H. pylori infection. Dietary factors in humans are increasingly recognized as being important factors in modulating progression and severity of H. pylori-induced gastric cancer. Studies using rodent models to verify and help explain mechanisms whereby various dietary ingredients impact disease outcome should continue to be extremely productive. PMID:24301796

Review of risk factors for human echinococcosis prevalence on the Qinghai-Tibet Plateau, China: a prospective for control options

PubMed Central

2014-01-01

Objective Echinococcosis is a major parasitic zoonosis of public health importance in western China. In 2004, the Chinese Ministry of Health estimated that 380,000 people had the disease in the region. The Qinghai-Tibet Plateau is highly co-endemic with both alveolar echinococcosis (AE) and cystic echinococcosis (CE). In the past years, the Chinese government has been increasing the financial support to control the diseases in this region. Therefore, it is very important to identify the significant risk factors of the diseases by reviewing studies done in the region in the past decade to help policymakers design appropriate control strategies. Review Selection criteria for which literature to review were firstly defined. Medline, CNKI (China National Knowledge Infrastructure), and Google Scholar were systematically searched for literature published between January 2000 and July 2011. Significant risk factors found by single factor and/or multiple factors analysis were listed, counted, and summarized. Literature was examined to check the comparability of the data; age and sex specific prevalence with same data structures were merged and used for further analysis. A variety of assumed social, economical, behavioral, and ecological risk factors were studied on the Plateau. Those most at risk were Tibetan herdsmen, the old and female in particular. By analyzing merged comparable data, it was found that females had a significant higher prevalence, and a positive linearity relationship existed between echinococcosis prevalence and increasing age. In terms of behavioral risk factors, playing with dogs was mostly correlated with CE and/or AE prevalence. In terms of hygiene, employing ground water as the drinking water source was significantly correlated with CE and AE prevalence. For definitive hosts, dog related factors were most frequently identified with prevalence of CE or/and AE; fox was a potential risk factor for AE prevalence only. Overgrazing and deforestation were significant for AE prevalence only. Conclusion Tibetan herdsmen communities were at the highest risk of echinococcosis prevalence and should be the focus of echinococcosis control. Deworming both owned and stray dogs should be a major measure for controlling echinococcosis; treatment of wild definitive hosts should also be considered for AE endemic areas. Health education activities should be in concert with the local people’s education backgrounds and languages in order to be able to improve behaviors. Further researches are needed to clarify the importance of wild hosts for AE/CE prevalence, the extent and range of the impacts of ecologic changes (overgrazing and deforestation) on the AE prevalence, and risk factors in Tibet. PMID:24475907

Review of risk factors for human echinococcosis prevalence on the Qinghai-Tibet Plateau, China: a prospective for control options.

PubMed

Wang, Qian; Huang, Yan; Huang, Liang; Yu, Wenjie; He, Wei; Zhong, Bo; Li, Wei; Zeng, Xiangman; Vuitton, Dominique A; Giraudoux, Patrick; Craig, Philip S; Wu, Weiping

2014-01-29

Echinococcosis is a major parasitic zoonosis of public health importance in western China. In 2004, the Chinese Ministry of Health estimated that 380,000 people had the disease in the region. The Qinghai-Tibet Plateau is highly co-endemic with both alveolar echinococcosis (AE) and cystic echinococcosis (CE). In the past years, the Chinese government has been increasing the financial support to control the diseases in this region. Therefore, it is very important to identify the significant risk factors of the diseases by reviewing studies done in the region in the past decade to help policymakers design appropriate control strategies. Selection criteria for which literature to review were firstly defined. Medline, CNKI (China National Knowledge Infrastructure), and Google Scholar were systematically searched for literature published between January 2000 and July 2011. Significant risk factors found by single factor and/or multiple factors analysis were listed, counted, and summarized. Literature was examined to check the comparability of the data; age and sex specific prevalence with same data structures were merged and used for further analysis.A variety of assumed social, economical, behavioral, and ecological risk factors were studied on the Plateau. Those most at risk were Tibetan herdsmen, the old and female in particular. By analyzing merged comparable data, it was found that females had a significant higher prevalence, and a positive linearity relationship existed between echinococcosis prevalence and increasing age. In terms of behavioral risk factors, playing with dogs was mostly correlated with CE and/or AE prevalence. In terms of hygiene, employing ground water as the drinking water source was significantly correlated with CE and AE prevalence. For definitive hosts, dog related factors were most frequently identified with prevalence of CE or/and AE; fox was a potential risk factor for AE prevalence only. Overgrazing and deforestation were significant for AE prevalence only. Tibetan herdsmen communities were at the highest risk of echinococcosis prevalence and should be the focus of echinococcosis control. Deworming both owned and stray dogs should be a major measure for controlling echinococcosis; treatment of wild definitive hosts should also be considered for AE endemic areas. Health education activities should be in concert with the local people's education backgrounds and languages in order to be able to improve behaviors. Further researches are needed to clarify the importance of wild hosts for AE/CE prevalence, the extent and range of the impacts of ecologic changes (overgrazing and deforestation) on the AE prevalence, and risk factors in Tibet.

Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health.

PubMed

Ha, Connie W Y; Lam, Yan Y; Holmes, Andrew J

2014-11-28

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.

Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

PubMed Central

Ha, Connie WY; Lam, Yan Y; Holmes, Andrew J

2014-01-01

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

Parasite effects on isopod feeding rates can alter the host's functional role in a natural stream ecosystem.

PubMed

Hernandez, Alexander D; Sukhdeo, Michael V K

2008-05-01

Changes to host behaviour as a consequence of infection are common in many parasite-host associations, but their effects on the functional role hosts play within ecosystems are rarely quantified. This study reports that helminth parasites significantly decrease consumption of detritus by their isopod hosts in laboratory experiments. Natural host and parasite densities across eight contiguous seasons were used to estimate effects on the amount of stream detritus-energy processed. Extrapolations using mass-specific processing rates from laboratory results to field patterns suggest that the effects of the parasites occur year round but the greatest impact on the amount of detritus processed by isopods occurs in the autumn when the bulk of leaf detritus enters the stream, and when parasite prevalence in the isopod population is high. Parasites have a lesser impact on the amount of detritus processed in spring and summer when isopods are most abundant, when parasite prevalence is not high, and when fish predation on isopods is high. These results support the idea that parasites can affect the availability of resources critical to other species by altering behaviours related to the functional role hosts play in ecosystems, and suggest that seasonality may be an important factor to consider in the dynamics of these parasite-host interactions.

Reducing tick burdens on chicks by treating breeding female grouse with permethrin

USDA-ARS?s Scientific Manuscript database

Ticks are important arthropod vectors of diseases of human, livestock, and wildlife hosts. In the United Kingdom, the sheep tick (Ixodes ricinus) is increasingly recognized as a main limiting factor of red grouse (Lagopus lagopus) populations, a game bird of high economic value. We evaluated the e...

Random T-DNA mutagenesis identifies a Cu-Zn-superoxide dismutase gene as a virulence factor of Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

The Ascomycetous fungus Sclerotinia sclerotiorum is a devastating pathogen capable of infecting more than 400 plant species including many economically important crops. In order to gain a better mechanistic understanding of its non-specific host-pathogen interactions, random mutagenesis through Agro...

Region, landscape, and host plant effects on reproduction by a mobile, multivoltine arthropod herbivore

USDA-ARS?s Scientific Manuscript database

Community structure, species abundance, and biotic interactions of invertebrate species in farmlands are influenced by larger-scale processes at region and landscape levels. While previous work makes clear the importance of landscape factors for natural enemy populations, relatively less is known ab...

Induction of virulence factors in Giardia duodenalis independent of host attachment

PubMed Central

Emery, Samantha J.; Mirzaei, Mehdi; Vuong, Daniel; Pascovici, Dana; Chick, Joel M.; Lacey, Ernest; Haynes, Paul A.

2016-01-01

Giardia duodenalis is responsible for the majority of parasitic gastroenteritis in humans worldwide. Host-parasite interaction models in vitro provide insights into disease and virulence and help us to understand pathogenesis. Using HT-29 intestinal epithelial cells (IEC) as a model we have demonstrated that initial sensitisation by host secretions reduces proclivity for trophozoite attachment, while inducing virulence factors. Host soluble factors triggered up-regulation of membrane and secreted proteins, including Tenascins, Cathepsin-B precursor, cystatin, and numerous Variant-specific Surface Proteins (VSPs). By comparison, host-cell attached trophozoites up-regulated intracellular pathways for ubiquitination, reactive oxygen species (ROS) detoxification and production of pyridoxal phosphate (PLP). We reason that these results demonstrate early pathogenesis in Giardia involves two independent host-parasite interactions. Motile trophozoites respond to soluble secreted signals, which deter attachment and induce expression of virulence factors. Trophozoites attached to host cells, in contrast, respond by up-regulating intracellular pathways involved in clearance of ROS, thus anticipating the host defence response. PMID:26867958

Modeling Occupancy of Hosts by Mistletoe Seeds after Accounting for Imperfect Detectability

PubMed Central

Fadini, Rodrigo F.; Cintra, Renato

2015-01-01

The detection of an organism in a given site is widely used as a state variable in many metapopulation and epidemiological studies. However, failure to detect the species does not necessarily mean that it is absent. Assessing detectability is important for occupancy (presence—absence) surveys; and identifying the factors reducing detectability may help improve survey precision and efficiency. A method was used to estimate the occupancy status of host trees colonized by mistletoe seeds of Psittacanthus plagiophyllus as a function of host covariates: host size and presence of mistletoe infections on the same or on the nearest neighboring host (the cashew tree Anacardium occidentale). The technique also evaluated the effect of taking detectability into account for estimating host occupancy by mistletoe seeds. Individual host trees were surveyed for presence of mistletoe seeds with the aid of two or three observers to estimate detectability and occupancy. Detectability was, on average, 17% higher in focal-host trees with infected neighbors, while decreased about 23 to 50% from smallest to largest hosts. The presence of mistletoe plants in the sample tree had negligible effect on detectability. Failure to detect hosts as occupied decreased occupancy by 2.5% on average, with maximum of 10% for large and isolated hosts. The method presented in this study has potential for use with metapopulation studies of mistletoes, especially those focusing on the seed stage, but also as improvement of accuracy in occupancy models estimates often used for metapopulation dynamics of tree-dwelling plants in general. PMID:25973754

Influential Parameters for the Analysis of Intracellular Parasite Metabolomics.

PubMed

Carey, Maureen A; Covelli, Vincent; Brown, Audrey; Medlock, Gregory L; Haaren, Mareike; Cooper, Jessica G; Papin, Jason A; Guler, Jennifer L

2018-04-25

Metabolomics is increasingly popular for the study of pathogens. For the malaria parasite Plasmodium falciparum , both targeted and untargeted metabolomics have improved our understanding of pathogenesis, host-parasite interactions, and antimalarial drug treatment and resistance. However, purification and analysis procedures for performing metabolomics on intracellular pathogens have not been explored. Here, we purified in vitro -grown ring-stage intraerythrocytic P. falciparum parasites for untargeted metabolomics studies; the small size of this developmental stage amplifies the challenges associated with metabolomics studies as the ratio between host and parasite biomass is maximized. Following metabolite identification and data preprocessing, we explored multiple confounding factors that influence data interpretation, including host contamination and normalization approaches (including double-stranded DNA, total protein, and parasite numbers). We conclude that normalization parameters have large effects on differential abundance analysis and recommend the thoughtful selection of these parameters. However, normalization does not remove the contribution from the parasite's extracellular environment (culture media and host erythrocyte). In fact, we found that extraparasite material is as influential on the metabolome as treatment with a potent antimalarial drug with known metabolic effects (artemisinin). Because of this influence, we could not detect significant changes associated with drug treatment. Instead, we identified metabolites predictive of host and medium contamination that could be used to assess sample purification. Our analysis provides the first quantitative exploration of the effects of these factors on metabolomics data analysis; these findings provide a basis for development of improved experimental and analytical methods for future metabolomics studies of intracellular organisms. IMPORTANCE Molecular characterization of pathogens such as the malaria parasite can lead to improved biological understanding and novel treatment strategies. However, the distinctive biology of the Plasmodium parasite, including its repetitive genome and the requirement for growth within a host cell, hinders progress toward these goals. Untargeted metabolomics is a promising approach to learn about pathogen biology. By measuring many small molecules in the parasite at once, we gain a better understanding of important pathways that contribute to the parasite's response to perturbations such as drug treatment. Although increasingly popular, approaches for intracellular parasite metabolomics and subsequent analysis are not well explored. The findings presented in this report emphasize the critical need for improvements in these areas to limit misinterpretation due to host metabolites and to standardize biological interpretation. Such improvements will aid both basic biological investigations and clinical efforts to understand important pathogens. Copyright © 2018 Carey et al.

Unraveling the Host Plant Alternation of Cacopsylla pruni – Adults but Not Nymphs Can Survive on Conifers Due to Phloem/Xylem Composition

PubMed Central

Gallinger, Jannicke; Gross, Jürgen

2018-01-01

Plant sap feeding insects like psyllids are known to be vectors of phloem dwelling bacteria (‘Candidatus Phytoplasma’ and ‘Ca. Liberibacter’), plant pathogens which cause severe diseases and economically important crop damage. Some univoltine psyllid species have a particular life cycle, within one generation they alternate two times between different host plant species. The plum psyllid Cacopsylla pruni, the vector of European Stone Fruit Yellows (ESFY), one of the most serious pests in European fruit production, migrates to stone fruit orchards (Prunus spp.) for mating and oviposition in early spring. The young adults of the new generation leave the Prunus trees in summer and emigrate to their overwintering hosts like spruce and other conifers. Very little is known about the factors responsible for the regulation of migration, reasons for host alternation, and the behavior of psyllids during their phase of life on conifers. Because insect feeding behavior and host acceptance is driven by different biotic factors, such as olfactory and gustatory cues as well as mechanical barriers, we carried out electrical penetration graph (EPG) recordings and survival bioassays with C. pruni on different conifer species as potential overwintering hosts and analyzed the chemical composition of the respective plant saps. We are the first to show that migrating psyllids do feed on overwintering hosts and that nymphs are able to ingest phloem and xylem sap of coniferous trees, but cannot develop on conifer diet. Analyses of plant saps reveal qualitative differences in the chemical composition between coniferous trees and Prunus as well as within conifer species. These differences are discussed with regard to nutritional needs of psyllid nymphs for proper development, overwintering needs of adults and restriction of ‘Ca. P. prunorum’ to Prunus phloem. PMID:29706983

Environment-related and host-related factors affecting the occurrence of lice on rodents in Central Europe.

PubMed

Stanko, Michal; Fričová, Jana; Miklisová, Dana; Khokhlova, Irina S; Krasnov, Boris R

2015-06-01

We studied the effects of environment- (habitat, season) and host-related (sex, body mass) factors on the occurrence of four species of lice (Insecta:Phthiraptera:Anoplura) on six rodent species (Rodentia:Muridae). We asked how these factors influence the occurrence of lice on an individual host and whether different rodent-louse associations demonstrate consistent trends in these effects. We found significant effects of at least one environment-related and at least one host-related factor on the louse occurrence in five of six host-louse associations. The effect of habitat was significant in two associations with the occurrence of lice being more frequent in lowland than in mountain habitats. The effect of season was significant in five associations with a higher occurrence of infestation during the warm season in four associations and the cold season in one association. Host sex affected significantly the infestation by lice in three associations with a higher frequency of infestation in males. Host body mass affected the occurrence of lice in all five associations, being negative in wood mice and positive in voles. In conclusion, lice were influenced not only by the host- but also by environment-related factors. The effects of the latter could be mediated via life history parameters of a host.

Implications of spatial patterns of roosting and movements of American robins for West Nile virus transmission.

PubMed

Benson, Thomas J; Ward, Michael P; Lampman, Richard L; Raim, Arlo; Weatherhead, Patrick J

2012-10-01

The arrival of West Nile virus (WNV) in North America has led to interest in the interaction between birds, the amplification hosts of WNV, and Culex mosquitoes, the primary WNV vectors. American robins (Turdus migratorius) are particularly important amplification hosts of WNV, and because the vector Culex mosquitoes are primarily nocturnal and feed on roosting birds, robin communal roosting behavior may play an important role in the transmission ecology of WNV. Using data from 43 radio-tracked individuals, we determined spatial and temporal patterns of robin roosting behavior, and how these patterns related to the distribution of WNV-infected mosquitoes. Use of the communal roost and fidelity to foraging areas was highly variable both within and among individual robins, and differed markedly from patterns documented in a previous study of robin roosting. Although there were clear seasonal patterns to both robin roosting and WNV occurrence, there was no significant relationship between communal roosting by robins and temporal or spatial patterns of WNV-positive mosquitoes. Our results suggest that, although robins may be important as WNV hosts, communal roosts are not necessarily important for WNV amplification. Other factors, including the availability and distribution of high-quality mosquito habitat and favorable weather for mosquito reproduction, may influence the importance of robin roosts for local WNV amplification and transmission.

Aphid (Myzus persicae) feeding on the parasitic plant dodder (Cuscuta australis) activates defense responses in both the parasite and soybean host.

PubMed

Zhuang, Huifu; Li, Juan; Song, Juan; Hettenhausen, Christian; Schuman, Meredith C; Sun, Guiling; Zhang, Cuiping; Li, Jing; Song, Dunlun; Wu, Jianqiang

2018-06-01

Dodders (Cuscuta spp.) are shoot holoparasites, whose haustoria penetrate host tissues to enable fusion between the parasite and host vascular systems, allowing Cuscuta to extract water, nutrients and other molecules from hosts. Aphids are piercing-sucking herbivores that use specialized stylets to feed on phloem sap. Aphids are known to feed on Cuscuta, but how Cuscuta and its host plant respond to aphids attacking the parasite was unknown. Phytohormone quantification, transcriptomic analysis and bioassays were performed to determine the responses of Cuscuta australis and its soybean (Glycine max) hosts to the feeding of green peach aphid (GPA; Myzus persicae) on C. australis. Decreased salicylic acid levels and 172 differentially expressed genes (DEGs) were found in GPA-attacked C. australis, and the soybean hosts exhibited increased jasmonic acid contents and 1015 DEGs, including > 100 transcription factor genes. Importantly, GPA feeding on C. australis increased the resistance of the soybean host to subsequent feeding by the leafworm Spodoptera litura and soybean aphid Aphis glycines, resulting in 21% decreased leafworm mass and 41% reduced aphid survival rate. These data strongly suggest that GPA feeding on Cuscuta induces a systemic signal, which is translocated to hosts and activates defense against herbivores. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Host selection by the shiny cowbird

USGS Publications Warehouse

Wiley, J.W.

1988-01-01

Factors important in Shiny Cowbird (Molothrus bonariensis) host selection were examined within the mangrove community in Puerto Rico. Cowbirds did not parasitize birds in proportion to their abundance. The cowbird breeding season coincided with those of its major hosts, which were 'high-quality' foster species (i.e., species that fledge .gtoreq. 55% of cowbirds hatched: Yellow Warbler, Dendroica petechia; Yellow-shouldered Blackbird, Agelaius xanthomus; Black-whiskered Vireo, Vireo altiloquus; Black-cowled Oriole, Icterus dominicensis; Peurto Rican Flycatcher, Myiarchus antillarum; Troupial, Icterus icterus), and did not extend into other periods even though nests of 'low-quality: species (i.e., species that fledge < 55% of cowbird chicks that hatched: Bronze Mannikin, Lonchura cucullata; Greater Antillean Grackle, Quiscalus niger; Gray Kingbird, Tyrannus dominicensis; Northern Mockingbird, Mimus polyglottos; Red-legged Thrush, Turdus plumbeus) were available. Shiny Cowbird food habits and egg size were similar to those of their hosts, suggesting that cowbirds choose hosts partly on the basis of this combination. Cowbirds located host nests primarily by cryptically watching activities of birds in likely habitats. Other nest locating strategies were active searching of suitable habitat and 'flushing' of hosts by the cowbird's noisy approach. Cowbirds closely monitored nest status with frequent visits that peaked on the host's first day of egg laying. Hosts using covered nests (e.g., cavities, domed nests) were as vulnerable to cowbird parasitism as those building open nests.

Deconstructing the Bat Skin Microbiome: Influences of the Host and the Environment.

PubMed

Avena, Christine V; Parfrey, Laura Wegener; Leff, Jonathan W; Archer, Holly M; Frick, Winifred F; Langwig, Kate E; Kilpatrick, A Marm; Powers, Karen E; Foster, Jeffrey T; McKenzie, Valerie J

2016-01-01

Bats are geographically widespread and play an important role in many ecosystems, but relatively little is known about the ecology of their associated microbial communities and the role microbial taxa play in bat health, development, and evolution. Moreover, few vertebrate animal skin microbiomes have been comprehensively assessed, and thus characterizing the bat skin microbiome will yield valuable insight into the variability of vertebrate skin microbiomes as a whole. The recent emergence of the skin fungal disease white-nose syndrome highlights the potentially important role bat skin microbial communities could play in bat health. Understanding the determinant of bat skin microbial communities could provide insight into important factors allowing individuals to persist with disease. We collected skin swabs from a total of 11 bat species from the eastern United States ( n = 45) and Colorado ( n = 119), as well as environmental samples ( n = 38) from a subset of sites, and used 16S rRNA marker gene sequencing to observe bacterial communities. In addition, we conducted a literature survey to compare the skin microbiome across vertebrate groups, including the bats presented in this study. Host species, region, and site were all significant predictors of the variability across bat skin bacterial communities. Many bacterial taxa were found both on bats and in the environment. However, some bacterial taxa had consistently greater relative abundances on bat skin relative to their environments. Bats shared many of their abundant taxa with other vertebrates, but also hosted unique bacterial lineages such as the class Thermoleophilia (Actinobacteria). A strong effect of site on the bat skin microbiome indicates that the environment very strongly influences what bacteria are present on bat skin. Bat skin microbiomes are largely composed of site-specific microbiota, but there do appear to be important host-specific taxa. How this translates to differences in host-microbial interactions and bat health remains an important knowledge gap, but this work suggests that habitat variability is very important. We identify some bacterial groups that are more consistent on bats despite site differences, and these may be important ones to study in terms of their function as potential core microbiome members.

Deconstructing the Bat Skin Microbiome: Influences of the Host and the Environment

PubMed Central

Avena, Christine V.; Parfrey, Laura Wegener; Leff, Jonathan W.; Archer, Holly M.; Frick, Winifred F.; Langwig, Kate E.; Kilpatrick, A. Marm; Powers, Karen E.; Foster, Jeffrey T.; McKenzie, Valerie J.

2016-01-01

Bats are geographically widespread and play an important role in many ecosystems, but relatively little is known about the ecology of their associated microbial communities and the role microbial taxa play in bat health, development, and evolution. Moreover, few vertebrate animal skin microbiomes have been comprehensively assessed, and thus characterizing the bat skin microbiome will yield valuable insight into the variability of vertebrate skin microbiomes as a whole. The recent emergence of the skin fungal disease white-nose syndrome highlights the potentially important role bat skin microbial communities could play in bat health. Understanding the determinant of bat skin microbial communities could provide insight into important factors allowing individuals to persist with disease. We collected skin swabs from a total of 11 bat species from the eastern United States (n = 45) and Colorado (n = 119), as well as environmental samples (n = 38) from a subset of sites, and used 16S rRNA marker gene sequencing to observe bacterial communities. In addition, we conducted a literature survey to compare the skin microbiome across vertebrate groups, including the bats presented in this study. Host species, region, and site were all significant predictors of the variability across bat skin bacterial communities. Many bacterial taxa were found both on bats and in the environment. However, some bacterial taxa had consistently greater relative abundances on bat skin relative to their environments. Bats shared many of their abundant taxa with other vertebrates, but also hosted unique bacterial lineages such as the class Thermoleophilia (Actinobacteria). A strong effect of site on the bat skin microbiome indicates that the environment very strongly influences what bacteria are present on bat skin. Bat skin microbiomes are largely composed of site-specific microbiota, but there do appear to be important host-specific taxa. How this translates to differences in host-microbial interactions and bat health remains an important knowledge gap, but this work suggests that habitat variability is very important. We identify some bacterial groups that are more consistent on bats despite site differences, and these may be important ones to study in terms of their function as potential core microbiome members. PMID:27909426

Antimicrobial Peptides and Wound Healing: Biological and Therapeutic Considerations

PubMed Central

Mangoni, Maria Luisa; McDermott, Alison M.; Zasloff, Michael

2016-01-01

Repair of tissue wounds is a fundamental process to re-establish tissue integrity and regular function. Importantly, infection is a major factor that hinders wound healing. Multicellular organisms have evolved an arsenal of host-defence molecules, including antimicrobial peptides (AMPs), aimed at controlling microbial proliferation and at modulating the host's immune response to a variety of biological or physical insults. In this brief review we provide the evidence for a role of AMPs as endogenous mediators of wound healing and their promising therapeutic potential for treatment of non-life threatening skin and other epithelial injuries. PMID:26738772

Laboratory Maintenance of Helicobacter Species

PubMed Central

Blanchard, Thomas G.; Nedrud, John G.

2012-01-01

Helicobacter species are Gram-negative bacteria that colonize the gastric or intestinal mucosa of many mammalian and avian hosts and induce histologic inflammation. The association of H. pylori with gastritis, peptic ulcer disease, and gastric cancers makes it a significant human pathogen. Animal models for these diseases are being used to explore the pathogenesis of H. pylori infection and in vaccine development (UNIT 8B.1). Both bacterial and host factors contribute to Helicobacter pathogenesis, and therefore the microbiology is very important. This unit describes how to culture the most commonly used gastric Helicobacter species, H. pylori, H. mustelae, and H. felis. PMID:18770594

The Battle between Rotavirus and Its Host for Control of the Interferon Signaling Pathway

PubMed Central

Arnold, Michelle M.; Sen, Adrish; Greenberg, Harry B.; Patton, John T.

2013-01-01

Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to ∼450,000 deaths globally each year. In this review, we discuss the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses. PMID:23359266

Characterization of ApB73, a virulence factor important for colonization of Zea mays by the smut Ustilago maydis.

PubMed

Stirnberg, Alexandra; Djamei, Armin

2016-12-01

The biotrophic fungus Ustilago maydis, the causal agent of corn smut disease, uses numerous small secreted effector proteins to suppress plant defence responses and reshape the host metabolism. However, the role of specific effectors remains poorly understood. Here, we describe the identification of ApB73 (Apathogenic in B73), an as yet uncharacterized protein essential for the successful colonization of maize by U. maydis. We show that apB73 is transcriptionally induced during the biotrophic stages of the fungal life cycle. The deletion of the apB73 gene results in cultivar-specific loss of gall formation in the host. The ApB73 protein is conserved among closely related smut fungi. However, using virulence assays, we show that only the orthologue of the maize-infecting head smut Sporisorium reilianum can complement the mutant phenotype of U. maydis. Although microscopy shows that ApB73 is secreted into the biotrophic interface, it seems to remain associated with fungal cell wall components or the fungal plasma membrane. Taken together, the results show that ApB73 is a conserved and important virulence factor of U. maydis that localizes to the interface between the pathogen and its host Zea mays. © 2016 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

Birds Shed RNA-Viruses According to the Pareto Principle

PubMed Central

Jankowski, Mark D.; Williams, Christopher J.; Fair, Jeanne M.; Owen, Jennifer C.

2013-01-01

A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian) – pathogen (RNA-virus) studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality) was 0.687 (0.036 SEM), and that 22.0% (0.90 SEM) of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics. PMID:23991129

Sampling locality is more detectable than taxonomy or ecology in the gut microbiota of the brood-parasitic Brown-headed Cowbird (Molothrus ater).

PubMed

Hird, Sarah M; Carstens, Bryan C; Cardiff, Steven W; Dittmann, Donna L; Brumfield, Robb T

2014-01-01

Brown-headed Cowbirds (Molothrus ater) are the most widespread avian brood parasite in North America, laying their eggs in the nests of approximately 250 host species that raise the cowbird nestlings as their own. It is currently unknown how these heterospecific hosts influence the cowbird gut microbiota relative to other factors, such as the local environment and genetics. We test a Nature Hypothesis (positing the importance of cowbird genetics) and a Nurture Hypothesis (where the host parents are most influential to cowbird gut microbiota) using the V6 region of 16S rRNA as a microbial fingerprint of the gut from 32 cowbird samples and 16 potential hosts from nine species. We test additional hypotheses regarding the influence of the local environment and age of the birds. We found no evidence for the Nature Hypothesis and little support for the Nurture Hypothesis. Cowbird gut microbiota did not form a clade, but neither did members of the host species. Rather, the physical location, diet and age of the bird, whether cowbird or host, were the most significant categorical variables. Thus, passerine gut microbiota may be most strongly influenced by environmental factors. To put this variation in a broader context, we compared the bird data to a fecal microbiota dataset of 38 mammal species and 22 insect species. Insects were always the most variable; on some axes, we found more variation within cowbirds than across all mammals. Taken together, passerine gut microbiota may be more variable and environmentally determined than other taxonomic groups examined to date.

Sampling locality is more detectable than taxonomy or ecology in the gut microbiota of the brood-parasitic Brown-headed Cowbird (Molothrus ater)

PubMed Central

Carstens, Bryan C.; Cardiff, Steven W.; Dittmann, Donna L.; Brumfield, Robb T.

2014-01-01

Brown-headed Cowbirds (Molothrus ater) are the most widespread avian brood parasite in North America, laying their eggs in the nests of approximately 250 host species that raise the cowbird nestlings as their own. It is currently unknown how these heterospecific hosts influence the cowbird gut microbiota relative to other factors, such as the local environment and genetics. We test a Nature Hypothesis (positing the importance of cowbird genetics) and a Nurture Hypothesis (where the host parents are most influential to cowbird gut microbiota) using the V6 region of 16S rRNA as a microbial fingerprint of the gut from 32 cowbird samples and 16 potential hosts from nine species. We test additional hypotheses regarding the influence of the local environment and age of the birds. We found no evidence for the Nature Hypothesis and little support for the Nurture Hypothesis. Cowbird gut microbiota did not form a clade, but neither did members of the host species. Rather, the physical location, diet and age of the bird, whether cowbird or host, were the most significant categorical variables. Thus, passerine gut microbiota may be most strongly influenced by environmental factors. To put this variation in a broader context, we compared the bird data to a fecal microbiota dataset of 38 mammal species and 22 insect species. Insects were always the most variable; on some axes, we found more variation within cowbirds than across all mammals. Taken together, passerine gut microbiota may be more variable and environmentally determined than other taxonomic groups examined to date. PMID:24711971

The effect of dietary antioxidant supplementation in a vertebrate host on the infection dynamics and transmission of avian malaria to the vector.

PubMed

Delhaye, Jessica; Glaizot, Olivier; Christe, Philippe

2018-05-09

Host susceptibility to parasites is likely to be influenced by intrinsic factors, such as host oxidative status determined by the balance between pro-oxidant production and antioxidant defences. As a result, host oxidative status acts as an environmental factor for parasites and may constrain parasite development. We evaluated the role of host oxidative status on infection dynamics of an avian malarial parasite by providing canaries (Serinus canaria) with an antioxidant supplementation composed of vitamin E (a lipophilic antioxidant) and olive oil, a source of monounsaturated fatty acids. Another group received a standard, non-supplemented food. Half of the birds in each group where then infected with the haemosporidian parasite, Plasmodium relictum. We monitored the parasitaemia, haematocrit level, and red cell membrane resistance, as well as the transmission success of the parasite to its mosquito vector, Culex pipiens. During the acute phase, the negative effect of the infection was more severe in the supplemented group, as shown by a lower haematocrit level. Parasitaemia was lower in the supplemented group during the chronic phase only. Mosquitoes fed on supplemented hosts were more often infected than mosquitoes fed on the control group. These results suggest that dietary antioxidant supplementation conferred protection against Plasmodium in the long term, at the expense of a short-term negative effect. Malaria parasites may take advantage of antioxidants, as shown by the increased transmission rate in the supplemented group. Overall, our results suggest an important role of oxidative status in infection outcome and parasite transmission.

Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.

PubMed

Hauser, Kurt F; Knapp, Pamela E

2014-01-01

Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.

Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors

PubMed Central

Hauser, Kurt F.; Knapp, Pamela E.

2015-01-01

Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome (neuroAIDS) and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain “connectome”. Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. PMID:25175867

[Predictive factors of virological response in chronically HCV infected].

PubMed

Lapiński, Tadeusz Wojciech; Flisiak, Robert

2012-09-01

Research on new antivirals drugs applied in the treatment of chronically HCV infected indicate that even the most perfect therapeutic molecules do not guarantee 100% efficacy. Since the beginning of the history of HCV infection treatment clinicians looked for predictors of treatment efficacy. Numerous studies confirm the high probability of cure in patients who cleared HCVinfectional 4 and 12 weeks of therapy. However despite of viral factors, recent research demonstrated predictive role of some host dependent factors. The most important role seems to play genetic factors including polymorphism rs12979860, as well as chemokins including first of all CXCL10 (IP-10). Very interesting seems to be also results of studies on association between vitamine D concentration and treatment efficacy. However in the future the most important predictive factor remain probably early on-treatment viral response.

Oral Microbial Ecology and the Role of Salivary Immunoglobulin A

PubMed Central

Marcotte, Harold; Lavoie, Marc C.

1998-01-01

In the oral cavity, indigenous bacteria are often associated with two major oral diseases, caries and periodontal diseases. These diseases seem to appear following an inbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. To define the process involved in caries and periodontal diseases, it is necessary to understand the ecology of the oral cavity and to identify the factors responsible for the transition of the oral microbiota from a commensal to a pathogenic relationship with the host. The regulatory forces influencing the oral ecosystem can be divided into three major categories: host related, microbe related, and external factors. Among host factors, secretory immunoglobulin A (SIgA) constitutes the main specific immune defense mechanism in saliva and may play an important role in the homeostasis of the oral microbiota. Naturally occurring SIgA antibodies that are reactive against a variety of indigenous bacteria are detectable in saliva. These antibodies may control the oral microbiota by reducing the adherence of bacteria to the oral mucosa and teeth. It is thought that protection against bacterial etiologic agents of caries and periodontal diseases could be conferred by the induction of SIgA antibodies via the stimulation of the mucosal immune system. However, elucidation of the role of the SIgA immune system in controlling the oral indigenous microbiota is a prerequisite for the development of effective vaccines against these diseases. The role of SIgA antibodies in the acquisition and the regulation of the indigenous microbiota is still controversial. Our review discusses the importance of SIgA among the multiple factors that control the oral microbiota. It describes the oral ecosystems, the principal factors that may control the oral microbiota, a basic knowledge of the secretory immune system, the biological functions of SIgA, and, finally, experiments related to the role of SIgA in oral microbial ecology. PMID:9529888

Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation

PubMed Central

Genoula, Melanie; Marín Franco, José Luis; Dupont, Maeva; Kviatcovsky, Denise; Milillo, Ayelén; Schierloh, Pablo; Moraña, Eduardo Jose; Poggi, Susana; Palmero, Domingo; Mata-Espinosa, Dulce; González-Domínguez, Erika; León Contreras, Juan Carlos; Barrionuevo, Paula; Rearte, Bárbara; Córdoba Moreno, Marlina Olyissa; Fontanals, Adriana; Crotta Asis, Agostina; Gago, Gabriela; Cougoule, Céline; Neyrolles, Olivier; Maridonneau-Parini, Isabelle; Sánchez-Torres, Carmen; Hernández-Pando, Rogelio; Vérollet, Christel; Lugo-Villarino, Geanncarlo; Sasiain, María del Carmen; Balboa, Luciana

2018-01-01

The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10−/− mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence. PMID:29593722

Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.

PubMed

Genoula, Melanie; Marín Franco, José Luis; Dupont, Maeva; Kviatcovsky, Denise; Milillo, Ayelén; Schierloh, Pablo; Moraña, Eduardo Jose; Poggi, Susana; Palmero, Domingo; Mata-Espinosa, Dulce; González-Domínguez, Erika; León Contreras, Juan Carlos; Barrionuevo, Paula; Rearte, Bárbara; Córdoba Moreno, Marlina Olyissa; Fontanals, Adriana; Crotta Asis, Agostina; Gago, Gabriela; Cougoule, Céline; Neyrolles, Olivier; Maridonneau-Parini, Isabelle; Sánchez-Torres, Carmen; Hernández-Pando, Rogelio; Vérollet, Christel; Lugo-Villarino, Geanncarlo; Sasiain, María Del Carmen; Balboa, Luciana

2018-01-01

The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14 + cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10 -/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.

Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation.

PubMed

Kilsgård, Ola; Karlsson, Christofer; Malmström, Erik; Malmström, Johan

2016-11-01

Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could predict the virulence of a S. pyogenes strain in mice and which could be used to identify key aspects of this bacteria's pathogenesis. Copyright © 2016 Elsevier GmbH. All rights reserved.

Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes

PubMed Central

Wong, Hui Hui; Kumar, Pankaj; Tay, Felicia Pei Ling; Moreau, Dimitri

2015-01-01

ABSTRACT Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics. IMPORTANCE Coronaviruses are RNA viruses representing a real threat for public health, as evidenced by SARS and the emerging MERS. However, cellular factors required for their replication are poorly understood. Using genome-wide siRNA screening, we identified novel genes supporting infectious bronchitis virus (IBV) replication in human cells. The several host factors identified in this study may provide directions for future research on targeted therapeutics. PMID:26311884

Environmental variables and definitive host distribution: a habitat suitability modelling for endohelminth parasites in the marine realm

PubMed Central

Kuhn, Thomas; Cunze, Sarah; Kochmann, Judith; Klimpel, Sven

2016-01-01

Marine nematodes of the genus Anisakis are common parasites of a wide range of aquatic organisms. Public interest is primarily based on their importance as zoonotic agents of the human Anisakiasis, a severe infection of the gastro-intestinal tract as result of consuming live larvae in insufficiently cooked fish dishes. The diverse nature of external impacts unequally influencing larval and adult stages of marine endohelminth parasites requires the consideration of both abiotic and biotic factors. Whereas abiotic factors are generally more relevant for early life stages and might also be linked to intermediate hosts, definitive hosts are indispensable for a parasite’s reproduction. In order to better understand the uneven occurrence of parasites in fish species, we here use the maximum entropy approach (Maxent) to model the habitat suitability for nine Anisakis species accounting for abiotic parameters as well as biotic data (definitive hosts). The modelled habitat suitability reflects the observed distribution quite well for all Anisakis species, however, in some cases, habitat suitability exceeded the known geographical distribution, suggesting a wider distribution than presently recorded. We suggest that integrative modelling combining abiotic and biotic parameters is a valid approach for habitat suitability assessments of Anisakis, and potentially other marine parasite species. PMID:27507328

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

PubMed Central

Netea, Mihai G.; Mouton, Johan W.; Melchers, Willem J. G.; Verweij, Paul E.; de Hoog, G. Sybren

2014-01-01

SUMMARY Among the melanized fungi, the so-called “black yeasts” and their filamentous relatives are particularly significant as agents of severe phaeohyphomycosis, chromoblastomycosis, and mycetoma in humans and animals. The pathogenicity and virulence of these fungi may differ significantly between closely related species. The factors which probably are of significance for pathogenicity include the presence of melanin and carotene, formation of thick cell walls and meristematic growth, presence of yeast-like phases, thermo- and perhaps also osmotolerance, adhesion, hydrophobicity, assimilation of aromatic hydrocarbons, and production of siderophores. Host defense has been shown to rely mainly on the ingestion and elimination of fungal cells by cells of the innate immune system, especially neutrophils and macrophages. However, there is increasing evidence supporting a role of T-cell-mediated immune responses, with increased interleukin-10 (IL-10) and low levels of gamma interferon (IFN-γ) being deleterious during the infection. There are no standardized therapies for treatment. It is therefore important to obtain in vitro susceptibilities of individual patients' fungal isolates in order to provide useful information for selection of appropriate treatment protocols. This article discusses the pathogenesis and host defense factors for these fungi and their severity, chronicity, and subsequent impact on treatment and prevention of diseases in human or animal hosts. PMID:24982320

Physiological Function of Rac Prophage During Biofilm Formation and Regulation of Rac Excision in Escherichia coli K-12.

PubMed

Liu, Xiaoxiao; Li, Yangmei; Guo, Yunxue; Zeng, Zhenshun; Li, Baiyuan; Wood, Thomas K; Cai, Xingsheng; Wang, Xiaoxue

2015-11-04

Rac or rac-like prophage harbors many genes with important physiological functions, while it remains excision-proficient in several bacterial strains including Escherichia coli, Salmonella spp. and Shigella spp. Here, we found that rac excision is induced during biofilm formation, and the isogenic stain without rac is more motile and forms more biofilms in nutrient-rich medium at early stages in E. coli K-12. Additionally, the presence of rac genes increases cell lysis during biofilm development. In most E. coli strains, rac is integrated into the ttcA gene which encodes a tRNA-thioltransferase. Rac excision in E. coli K-12 leads to a functional change of TtcA, which results in reduced fitness in the presence of carbenicillin. Additionally, we demonstrate that YdaQ (renamed as XisR) is the excisionase of rac in E. coli K-12, and that rac excision is induced by the stationary sigma factor RpoS through inducing xisR expression. Taken together, our results reveal that upon rac integration, not only are new genes introduced into the host, but also there is a functional change in a host enzyme. Hence, rac excision is tightly regulated by host factors to control its stability in the host genome under different stress conditions.

Physiological Function of Rac Prophage During Biofilm Formation and Regulation of Rac Excision in Escherichia coli K-12

PubMed Central

Liu, Xiaoxiao; Li, Yangmei; Guo, Yunxue; Zeng, Zhenshun; Li, Baiyuan; Wood, Thomas K.; Cai, Xingsheng; Wang, Xiaoxue

2015-01-01

Rac or rac-like prophage harbors many genes with important physiological functions, while it remains excision-proficient in several bacterial strains including Escherichia coli, Salmonella spp. and Shigella spp. Here, we found that rac excision is induced during biofilm formation, and the isogenic stain without rac is more motile and forms more biofilms in nutrient-rich medium at early stages in E. coli K-12. Additionally, the presence of rac genes increases cell lysis during biofilm development. In most E. coli strains, rac is integrated into the ttcA gene which encodes a tRNA-thioltransferase. Rac excision in E. coli K-12 leads to a functional change of TtcA, which results in reduced fitness in the presence of carbenicillin. Additionally, we demonstrate that YdaQ (renamed as XisR) is the excisionase of rac in E. coli K-12, and that rac excision is induced by the stationary sigma factor RpoS through inducing xisR expression. Taken together, our results reveal that upon rac integration, not only are new genes introduced into the host, but also there is a functional change in a host enzyme. Hence, rac excision is tightly regulated by host factors to control its stability in the host genome under different stress conditions. PMID:26530864

Environmental variables and definitive host distribution: a habitat suitability modelling for endohelminth parasites in the marine realm

NASA Astrophysics Data System (ADS)

Kuhn, Thomas; Cunze, Sarah; Kochmann, Judith; Klimpel, Sven

2016-08-01

Marine nematodes of the genus Anisakis are common parasites of a wide range of aquatic organisms. Public interest is primarily based on their importance as zoonotic agents of the human Anisakiasis, a severe infection of the gastro-intestinal tract as result of consuming live larvae in insufficiently cooked fish dishes. The diverse nature of external impacts unequally influencing larval and adult stages of marine endohelminth parasites requires the consideration of both abiotic and biotic factors. Whereas abiotic factors are generally more relevant for early life stages and might also be linked to intermediate hosts, definitive hosts are indispensable for a parasite’s reproduction. In order to better understand the uneven occurrence of parasites in fish species, we here use the maximum entropy approach (Maxent) to model the habitat suitability for nine Anisakis species accounting for abiotic parameters as well as biotic data (definitive hosts). The modelled habitat suitability reflects the observed distribution quite well for all Anisakis species, however, in some cases, habitat suitability exceeded the known geographical distribution, suggesting a wider distribution than presently recorded. We suggest that integrative modelling combining abiotic and biotic parameters is a valid approach for habitat suitability assessments of Anisakis, and potentially other marine parasite species.

Helminths and the IBD hygiene hypothesis.

PubMed

Weinstock, Joel V; Elliott, David E

2009-01-01

Helminths are parasitic animals that have evolved over 100,000,000 years to live in the intestinal track or other locations of their hosts. Colonization of humans with these organisms was nearly universal until the early 20th century. More than 1,000,000,000 people in less developed countries carry helminths even today. Helminths must quell their host's immune system to successfully colonize. It is likely that helminths sense hostile changes in the local host environment and take action to control such responses. Inflammatory bowel disease (IBD) probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The "IBD hygiene hypothesis" states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. Helminths interact with both host innate and adoptive immunity to stimulate immune regulatory circuitry and to dampen effector pathways that drive aberrant inflammation. The first prototype worm therapies directed against immunological diseases are now under study in the United States and various countries around the world. Additional studies are in the advanced planning stage.

Explaining variance of avian malaria infection in the wild: the importance of host density, habitat, individual life-history and oxidative stress.

PubMed

Isaksson, Caroline; Sepil, Irem; Baramidze, Vladimer; Sheldon, Ben C

2013-04-08

Avian malaria (Plasmodium sp.) is globally widespread, but considerable variation exists in infection (presence/absence) patterns at small spatial scales. This variation can be driven by variation in ecology, demography, and phenotypic characters, in particular those that influence the host's resistance. Generation of reactive oxygen species (ROS) is one of the host's initial immune responses to combat parasitic invasion. However, long-term ROS exposure can harm the host and the redox response therefore needs to be adjusted according to infection stage and host phenotype. Here we use experimental and correlational approaches to assess the relative importance of host density, habitat composition, individual level variation and redox physiology for Plasmodium infection in a wild population of great tits, Parus major. We found that 36% of the great tit population was infected with Plasmodium (22% P. relictum and 15% P. circumflexum prevalence) and that patterns of infection were Plasmodium species-specific. First, the infection of P. circumflexum was significantly higher in areas with experimental increased host density, whereas variation in P. relictum infection was mainly attributed to age, sex and reproduction. Second, great tit antioxidant responses - total and oxidizied glutathione - showed age- , sex- and Plasmodium species-specific patterns between infected and uninfected individuals, but reactive oxygen metabolites (ROM) showed only a weak explanatory power for patterns of P. relictum infection. Instead ROM significantly increased with Plasmodium parasitaemia. These results identify some key factors that influence Plasmodium infection in wild birds, and provide a potential explanation for the underlying physiological basis of recently documented negative effects of chronic avian malaria on survival and reproductive success.

A Comparison of Multiple Methods for Estimating Parasitemia of Hemogregarine Hemoparasites (Apicomplexa: Adeleorina) and Its Application for Studying Infection in Natural Populations

PubMed Central

Maia, João P.; Harris, D. James; Carranza, Salvador; Gómez-Díaz, Elena

2014-01-01

Identifying factors influencing infection patterns among hosts is critical for our understanding of the evolution and impact of parasitism in natural populations. However, the correct estimation of infection parameters depends on the performance of detection and quantification methods. In this study, we designed a quantitative PCR (qPCR) assay targeting the 18 S rRNA gene to estimate prevalence and intensity of Hepatozoon infection and compared its performance with microscopy and PCR. Using qPCR, we also compared various protocols that differ in the biological source and the extraction methods. Our results show that the qPCR approach on DNA extracted from blood samples, regardless of the extraction protocol, provided the most sensitive estimates of Hepatozoon infection parameters; while allowed us to differentiate between mixed infections of Adeleorinid (Hepatozoon) and Eimeriorinid (Schellackia and Lankesterella), based on the analysis of melting curves. We also show that tissue and saline methods can be used as low-cost alternatives in parasitological studies. The next step was to test our qPCR assay in a biological context, and for this purpose we investigated infection patterns between two sympatric lacertid species, which are naturally infected with apicomplexan hemoparasites, such as the genera Schellackia (Eimeriorina) and Hepatozoon (Adeleorina). From a biological standpoint, we found a positive correlation between Hepatozoon intensity of infection and host body size within each host species, being significantly higher in males, and higher in the smaller sized host species. These variations can be associated with a number of host intrinsic factors, like hormonal and immunological traits, that require further investigation. Our findings are relevant as they pinpoint the importance of accounting for methodological issues to better estimate infection in parasitological studies, and illustrate how between-host factors can influence parasite distributions in sympatric natural populations. PMID:24743340

A comparison of multiple methods for estimating parasitemia of hemogregarine hemoparasites (apicomplexa: adeleorina) and its application for studying infection in natural populations.

PubMed

Maia, João P; Harris, D James; Carranza, Salvador; Gómez-Díaz, Elena

2014-01-01

Identifying factors influencing infection patterns among hosts is critical for our understanding of the evolution and impact of parasitism in natural populations. However, the correct estimation of infection parameters depends on the performance of detection and quantification methods. In this study, we designed a quantitative PCR (qPCR) assay targeting the 18 S rRNA gene to estimate prevalence and intensity of Hepatozoon infection and compared its performance with microscopy and PCR. Using qPCR, we also compared various protocols that differ in the biological source and the extraction methods. Our results show that the qPCR approach on DNA extracted from blood samples, regardless of the extraction protocol, provided the most sensitive estimates of Hepatozoon infection parameters; while allowed us to differentiate between mixed infections of Adeleorinid (Hepatozoon) and Eimeriorinid (Schellackia and Lankesterella), based on the analysis of melting curves. We also show that tissue and saline methods can be used as low-cost alternatives in parasitological studies. The next step was to test our qPCR assay in a biological context, and for this purpose we investigated infection patterns between two sympatric lacertid species, which are naturally infected with apicomplexan hemoparasites, such as the genera Schellackia (Eimeriorina) and Hepatozoon (Adeleorina). From a biological standpoint, we found a positive correlation between Hepatozoon intensity of infection and host body size within each host species, being significantly higher in males, and higher in the smaller sized host species. These variations can be associated with a number of host intrinsic factors, like hormonal and immunological traits, that require further investigation. Our findings are relevant as they pinpoint the importance of accounting for methodological issues to better estimate infection in parasitological studies, and illustrate how between-host factors can influence parasite distributions in sympatric natural populations.

Invasion biology in non-free-living species: interactions between abiotic (climatic) and biotic (host availability) factors in geographical space in crayfish commensals (Ostracoda, Entocytheridae)

PubMed Central

Mestre, Alexandre; Aguilar-Alberola, Josep A; Baldry, David; Balkis, Husamettin; Ellis, Adam; Gil-Delgado, Jose A; Grabow, Karsten; Klobučar, Göran; Kouba, Antonín; Maguire, Ivana; Martens, Andreas; Mülayim, Ayşegül; Rueda, Juan; Scharf, Burkhard; Soes, Menno; S Monrós, Juan; Mesquita-Joanes, Francesc

2013-01-01

In invasion processes, both abiotic and biotic factors are considered essential, but the latter are usually disregarded when modeling the potential spread of exotic species. In the framework of set theory, interactions between biotic (B), abiotic (A), and movement-related (M) factors in the geographical space can be hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to estimate A and B areas. The main aim of our survey was to evaluate the interactions between abiotic (climatic) and biotic (host availability) factors in geographical space for exotic symbionts (i.e., non-free-living species), using ENM techniques combined with a BAM framework and using exotic Entocytheridae (Ostracoda) found in Europe as model organisms. We carried out an extensive survey to evaluate the distribution of entocytherids hosted by crayfish in Europe by checking 94 European localities and 12 crayfish species. Both exotic entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis, were widely distributed in W Europe living on the exotic crayfish species Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids were observed in the remaining crayfish species. The suitable area for A. sinuosa was mainly restricted by its own limitations to minimum temperatures in W and N Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere occidentalis was mostly restricted by host availability in circum-Mediterranean regions due to limitations of P. leniusculus to higher precipitation seasonality and maximum temperatures. The combination of ENMs with set theory allows studying the invasive biology of symbionts and provides clues about biogeographic barriers due to abiotic or biotic factors limiting the expansion of the symbiont in different regions of the invasive range. The relative importance of abiotic and biotic factors on geographical space can then be assessed and applied in conservation plans. This approach can also be implemented in other systems where the target species is closely interacting with other taxa. PMID:24455152

Acute radiation syndrome (ARS) - treatment of the reduced host defense.

PubMed

Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

2012-01-01

The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. Review of the current literature. The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage's important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250-400 μg GM-CSF/m(2) or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14-21 days. The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction.

Invasion biology in non-free-living species: interactions between abiotic (climatic) and biotic (host availability) factors in geographical space in crayfish commensals (Ostracoda, Entocytheridae).

PubMed

Mestre, Alexandre; Aguilar-Alberola, Josep A; Baldry, David; Balkis, Husamettin; Ellis, Adam; Gil-Delgado, Jose A; Grabow, Karsten; Klobučar, Göran; Kouba, Antonín; Maguire, Ivana; Martens, Andreas; Mülayim, Ayşegül; Rueda, Juan; Scharf, Burkhard; Soes, Menno; S Monrós, Juan; Mesquita-Joanes, Francesc

2013-12-01

In invasion processes, both abiotic and biotic factors are considered essential, but the latter are usually disregarded when modeling the potential spread of exotic species. In the framework of set theory, interactions between biotic (B), abiotic (A), and movement-related (M) factors in the geographical space can be hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to estimate A and B areas. The main aim of our survey was to evaluate the interactions between abiotic (climatic) and biotic (host availability) factors in geographical space for exotic symbionts (i.e., non-free-living species), using ENM techniques combined with a BAM framework and using exotic Entocytheridae (Ostracoda) found in Europe as model organisms. We carried out an extensive survey to evaluate the distribution of entocytherids hosted by crayfish in Europe by checking 94 European localities and 12 crayfish species. Both exotic entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis, were widely distributed in W Europe living on the exotic crayfish species Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids were observed in the remaining crayfish species. The suitable area for A. sinuosa was mainly restricted by its own limitations to minimum temperatures in W and N Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere occidentalis was mostly restricted by host availability in circum-Mediterranean regions due to limitations of P. leniusculus to higher precipitation seasonality and maximum temperatures. The combination of ENMs with set theory allows studying the invasive biology of symbionts and provides clues about biogeographic barriers due to abiotic or biotic factors limiting the expansion of the symbiont in different regions of the invasive range. The relative importance of abiotic and biotic factors on geographical space can then be assessed and applied in conservation plans. This approach can also be implemented in other systems where the target species is closely interacting with other taxa.

The obese gut microbiome across the epidemiologic transition.

PubMed

Dugas, Lara R; Fuller, Miles; Gilbert, Jack; Layden, Brian T

2016-01-01

The obesity epidemic has emerged over the past few decades and is thought to be a result of both genetic and environmental factors. A newly identified factor, the gut microbiota, which is a bacterial ecosystem residing within the gastrointestinal tract of humans, has now been implicated in the obesity epidemic. Importantly, this bacterial community is impacted by external environmental factors through a variety of undefined mechanisms. We focus this review on how the external environment may impact the gut microbiota by considering, the host's geographic location 'human geography', and behavioral factors (diet and physical activity). Moreover, we explore the relationship between the gut microbiota and obesity with these external factors. And finally, we highlight here how an epidemiologic model can be utilized to elucidate causal relationships between the gut microbiota and external environment independently and collectively, and how this will help further define this important new factor in the obesity epidemic.

Exploring Relationships between Host Genome and Microbiome: New Insights from Genome-Wide Association Studies

PubMed Central

Abdul-Aziz, Muslihudeen A.; Cooper, Alan; Weyrich, Laura S.

2016-01-01

As our understanding of the human microbiome expands, impacts on health and disease continue to be revealed. Alterations in the microbiome can result in dysbiosis, which has now been linked to subsequent autoimmune and metabolic diseases, highlighting the need to identify factors that shape the microbiome. Research has identified that the composition and functions of the human microbiome can be influenced by diet, age, sex, and environment. More recently, studies have explored how human genetic variation may also influence the microbiome. Here, we review several recent analytical advances in this new research area, including those that use genome-wide association studies to examine host genome–microbiome interactions, while controlling for the influence of other factors. We find that current research is limited by small sample sizes, lack of cohort replication, and insufficient confirmatory mechanistic studies. In addition, we discuss the importance of understanding long-term interactions between the host genome and microbiome, as well as the potential impacts of disrupting this relationship, and explore new research avenues that may provide information about the co-evolutionary history of humans and their microorganisms. PMID:27785127

A Proteomic Study of Clavibacter Michiganensis Subsp. Michiganensis Culture Supernatants

PubMed Central

Hiery, Eva; Poetsch, Ansgar; Moosbauer, Tanja; Amin, Bushra; Hofmann, Jörg; Burkovski, Andreas

2015-01-01

Clavibacter michiganensis, subsp. michiganensis is a Gram-positive plant pathogen infecting tomato (Solanum lycopersicum). Despite a considerable economic importance due to significant losses of infected plants and fruits, knowledge about virulence factors of C. michiganensis subsp. michiganensis and host-pathogen interactions on a molecular level are rather limited. In the study presented here, the proteome of culture supernatants from C. michiganensis subsp. michiganensis NCPPB382 was analyzed. In total, 1872 proteins were identified in M9 and 1766 proteins in xylem mimicking medium. Filtration of supernatants before protein precipitation reduced these to 1276 proteins in M9 and 976 proteins in the xylem mimicking medium culture filtrate. The results obtained indicate that C. michiganensis subsp. michiganensis reacts to a sucrose- and glucose-depleted medium similar to the xylem sap by utilizing amino acids and host cell polymers as well as their degradation products, mainly peptides, amino acids and various C5 and C6 sugars. Interestingly, the bacterium expresses the previously described virulence factors Pat-1 and CelA not exclusively after host cell contact in planta but already in M9 minimal and xylem mimicking medium. PMID:28248277

Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

PubMed

Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

2018-02-15

Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this concept needs expansion as the functions are more diverse. We showed that capsid protein VI regulates the antiviral response by modulation of the transcription factor Daxx during infection. Moreover, core protein VII interacts with SPOC1 restriction factor, which is beneficial for efficient viral gene expression. Here, we were able to show that core protein V also represents a novel substrate of the host SUMOylation machinery and contains several conserved SCMs; mutation of these consensus motifs reduced SUMOylation of the protein. Unexpectedly, we observed that introducing these mutations into HAdV promotes adenoviral replication. In conclusion, we offer novel insights into adenovirus core proteins and provide evidence that SUMOylation of HAdV factors regulates replication efficiency. Copyright © 2018 American Society for Microbiology.

Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of large DNA viruses infecting invertebrates.

PubMed

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts.

Candida albicans and Pseudomonas aeruginosa Interaction, with Focus on the Role of Eicosanoids

PubMed Central

Fourie, Ruan; Ells, Ruan; Swart, Chantel W.; Sebolai, Olihile M.; Albertyn, Jacobus; Pohl, Carolina H.

2016-01-01

Candida albicans is commonly found in mixed infections with Pseudomonas aeruginosa, especially in the lungs of cystic fibrosis (CF) patients. Both of these opportunistic pathogens are able to form resistant biofilms and frequently infect immunocompromised individuals. The interaction between these two pathogens, which includes physical interaction as well as secreted factors, is mainly antagonistic. In addition, research suggests considerable interaction with their host, especially with immunomodulatory lipid mediators, termed eicosanoids. Candida albicans and Pseudomonas aeruginosa are both able to utilize arachidonic acid (AA), liberated from the host cells during infection, to form eicosanoids. The production of these eicosanoids, such as Prostaglandin E2, by the host and the pathogens may affect the dynamics of polymicrobial infection and the outcome of infections. It is of considerable importance to elucidate the role of host-produced, as well as pathogen-produced eicosanoids in polymicrobial infection. This review will focus on in vitro as well as in vivo interaction between C. albicans and P. aeruginosa, paying special attention to the role of eicosanoids in the cross-talk between host and the pathogens. PMID:26955357

Ponderosa pine resin defenses and growth: Metrics matter

Treesearch

Sharon Hood; Anna Sala

2015-01-01

Bark beetles (Coleoptera: Curculionidae, Scolytinae) cause widespread tree mortality in coniferous forests worldwide. Constitutive and induced host defenses are important factors in an individual tree’s ability to survive an attack and in bottom-up regulation of bark beetle population dynamics, yet quantifying defense levels is often difficult. For example, in...

Predation and bark beetle dynamics

Treesearch

John D. Reeve

1997-01-01

Bark beetle populations may undergo dramatic fluctuations and are often important pests in coniferous forests.Their dynamics are thought to be primarily driven by factors affecting the resistance of the host tree to attack, i.e., bottom-up forces, while natural enemies are usually assigned a minor role in these systems.I present behavioral experiments that suggest that...

Genetic insights into Graminella nigrifrons competence for Maize fine streak virus infection and transmission

USDA-ARS?s Scientific Manuscript database

Insects are critical for the spread of most plant virus diseases, with >75% of plant viruses depending on an insects for transmission to new, uninfected hosts. However, little is known about the molecular and cellular factors in the insect that are important for virus transmission. The black-faced l...

A petunia ethylene-responsive element binding factor, PhERF2, plays an important role in antiviral RNA silencing

USDA-ARS?s Scientific Manuscript database

Virus-induced gene silencing (VIGS) is a useful technique for functional characterization of plant genes. However, the silencing efficiency of the VIGS system is variable largely depending on compatibility between the host and the virus. Antiviral RNA silencing is involved in plant antiviral defense...

Understanding the Symbolic Capital of Intercultural Interactions: A Case Study of International Students in Australia

ERIC Educational Resources Information Center

Pham, Lien; Tran, Ly

2015-01-01

Intercultural interaction plays an important role in contributing to international students' learning and wellbeing in the host country. While research on international students' intercultural interactions reveals multifaceted aspects of personal and social factors, there is a tendency to consider language barrier and cultural differences as…

Not so Splendid for the Gut Microbiota.

PubMed

Chassaing, Benoit; Gewirtz, Andrew T

2018-04-23

A critically important new study by leading inflammatory bowel disease (IBD) researcher Fabio Cominelli and colleagues reveals that, in mice, the artificial sweetener SPLENDA deleteriously impacts the intestinal microbiota in a manner that promotes Crohn's-type disease in genetically susceptible hosts. These results suggest that consumption of this product may be a risk factor for IBD.

Special feature: alien pests threatening biodiversity of forest ecosystems. Editorial.

Treesearch

Naoto Kamata; Kurt W. Gottschalk

2007-01-01

Throughout the world, biological invasions have become one of the most important factors threatening biodiversity. Many species are introduced into "a new world" accidentally or intentionally. Most fail to become established, but some become established, colonize, and start to increase and expand their ranges. Some invasive pathogens damage and kill host...

Die Virus-induzierten Lebererkrankungen des Menschen

NASA Astrophysics Data System (ADS)

Eisenburg, J.

1982-12-01

Although many viral agents may be associated with inflammatory hepatic changes, the vast majority of clinically important viral hepatitis is caused by hepatitis A, hepatitis B and the non A, non B agents. Infection of the liver of man by these hepatotropic agents is still a major public health problem in all parts of the world and constitutes a major hazard of the transfusion of blood and plasma derivatives. The magnitude of this hepatitis problem is not only documented by the about 200 million carriers of the hepatitis-B virus throughout the world, many of them asymptomatic, but also by the fact, that hepatitis B and non A, non B may progress to chronic liver disease, including cirrhosis and probably primary liver cancer. Potentially important pathogenetic determinants include viral factors such as subtype, dosage and mode of transmission and host factors such as age, sex, preexisting liver disease, coexisting non-liver disease (diabetes etc.), genetics and immune response to viral or autoantigens. As the virus itself seems not directly cytopathic, the diversity of lesions has been attributed to variation in the capacity of the host's response.

The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility.

PubMed

Escalante, Nichole K; Lemire, Paul; Cruz Tleugabulova, Mayra; Prescott, David; Mortha, Arthur; Streutker, Catherine J; Girardin, Stephen E; Philpott, Dana J; Mallevaey, Thierry

2016-12-12

The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1 -/- mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research. © 2016 Escalante et al.

STAT2-dependent immune responses ensure host survival despite the presence of a potent viral antagonist.

PubMed

Le-Trilling, Vu Thuy Khanh; Wohlgemuth, Kerstin; Rückborn, Meike U; Jagnjic, Andreja; Maaßen, Fabienne; Timmer, Lejla; Katschinski, Benjamin; Trilling, Mirko

2018-05-09

Pathogen encounter induces interferons which signal via Janus kinases and STAT transcription factors to establish an antiviral state. However, host and pathogens are situated in a continuous arms race which shapes host evolution towards optimized immune responses and the pathogens towards enhanced immune evasive properties.Mouse cytomegalovirus (MCMV) counteracts interferon responses by pM27-mediated degradation of STAT2 which directly affects the signaling of type I as well as type III interferons. Using MCMV mutants lacking M27 and mice lacking STAT2, we studied the opposing relationship between antiviral activities and viral antagonism in a natural host-pathogen pair in vitro and in vivo In contrast to wt-MCMV, ΔM27-MCMV was efficiently cleared from all organs within a few days in BALB/c, C57BL/6, and 129 mice, highlighting the general importance of STAT2 antagonism for MCMV replication. Despite this effective and relevant STAT2 antagonism, wt and STAT2-deficient mice exhibited fundamentally different susceptibilities to MCMV infections. MCMV replication was increased in all assessed organs (e.g. liver, spleen, lungs, and salivary glands) of STAT2-deficient mice, resulting in mortality during the first week after infection.Taken together, our study reveals the importance of cytomegaloviral interferon antagonism for viral replication as well as a pivotal role of the remaining STAT2 activity for host survival. This mutual influence establishes a stable evolutionary stand-off situation with fatal consequences when the equilibrium is disturbed. IMPORTANCE The host limits viral replication by interferons which signal via STAT proteins. Several viruses evolved antagonists targeting STATs to antagonize IFNs (e.g. cytomegaloviruses, Zika virus, Dengue virus, and several paramyxoviruses). We analyzed infections of mouse CMV expressing or lacking the STAT2 antagonist pM27 in STAT2-deficient and control mice to evaluate their importance for host and virus in vitro and in vivo The inability to counteract STAT2 directly translates into exaggerated IFN susceptibility in vitro and pronounced attenuation in vivo Thus, the antiviral activity mediated by IFNs via STAT2-dependent signaling drove the development of a potent MCMV-encoded STAT2 antagonist which became indispensable for efficient virus replication and spread to organs required for dissemination. Despite this clear impact of viral STAT2 antagonism, the host critically required the remaining STAT2 activity to prevent overt disease and mortality upon MCMV infection. Our findings highlight a remarkably delicate balance between host and virus. Copyright © 2018 Le-Trilling et al.

Mixed infections and the competitive fitness of faster-acting genetically modified viruses

PubMed Central

Zwart, Mark P; Van Der Werf, Wopke; Van Oers, Monique M; Hemerik, Lia; Van Lent, Jan M V; De Visser, J Arjan G M; Vlak, Just M; Cory, Jenny S

2009-01-01

Faster-acting recombinant baculoviruses have shown potential for improved suppression of insect pests, but their ecological impact on target and nontarget hosts and naturally occurring pathogens needs to be assessed. Previous studies have focused on the fitness of recombinants at the between-hosts level. However, the population structure of the transmission stages will also be decided by within-host selection. Here we have experimentally quantified the within-host competitive fitness of a fast-acting recombinant Autographa californica multicapsid nucleopolyhedrovirus missing the endogenous egt gene (vEGTDEL), by means of direct competition in single- and serial-passage experiments with its parental virus. Quantitative real-time PCR was employed to determine the ratio of these two viruses in passaged mixtures. We found that vEGTDEL had reduced within-host fitness: per passage the ratio of wild type to vEGTDEL was on average enhanced by a factor of 1.53 (single passage) and 1.68 (serial passage). There is also frequency-dependence: the higher the frequency of vEGTDEL, the stronger the selection against it is. Additionally, the virus ratio is a predictor of time to host death and virus yield. Our results show that egt is important to within-host fitness and allow for a more complete assessment of the ecological impact of recombinant baculovirus release. PMID:25567862

The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent.

PubMed

Hoffmann, Markus; González Hernández, Mariana; Berger, Elisabeth; Marzi, Andrea; Pöhlmann, Stefan

2016-01-01

Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.

The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent

PubMed Central

Hoffmann, Markus; González Hernández, Mariana; Berger, Elisabeth; Marzi, Andrea; Pöhlmann, Stefan

2016-01-01

Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species. PMID:26901159

Zoonotic potential of emerging paramyxoviruses: knowns and unknowns

PubMed Central

Thibault, Patricia A; Watkinson, Ruth E; Moreira-Soto, Andres; Drexler, Jan Felix; Lee, Benhur

2017-01-01

The risk of spillover of enzootic paramyxoviruses, and the susceptibility of recipient human and domestic animal populations, are defined by a broad collection of ecological and molecular factors that interact in ways that are not yet fully understood. Nipah and Hendra viruses were the first highly-lethal zoonotic paramyxoviruses discovered in modern times, but other paramyxoviruses from multiple genera are present in bats and other reservoirs that have unknown potential to spill over into humans. We outline our current understanding of paramyxovirus reservoir hosts and the ecological factors that may drive spillover, and we explore the molecular barriers to spillover that emergent paramyxoviruses may encounter. By outlining what is known about enzootic paramyxovirus receptor usage, mechanisms of innate immune evasion, and other host-specific interactions, we highlight the breadth of unexplored avenues that may be important in understanding paramyxovirus emergence. PMID:28433050

Porcine reproductive and respiratory syndrome virus infection induces both eIF2α-phosphorylation-dependent and -independent host translation shutoff.

PubMed

Li, Yang; Fang, Liurong; Zhou, Yanrong; Tao, Ran; Wang, Dang; Xiao, Shaobo

2018-06-13

Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has caused tremendous economic losses in the global swine industry since it was discovered in the late 1980s. Inducing host translation shutoff is a strategy used by many viruses to optimize their replication and spread. Here, we demonstrate that PRRSV infection causes host translation suppression, which is strongly dependent on viral replication. By screening PRRSV-encoded nonstructural proteins (nsps), we found that nsp2 participates in the induction of host translation shutoff and that its transmembrane (TM) domain is required for this process. Nsp2-induced translation suppression is independent of protein degradation pathways and the phosphorylation of eukaryotic initiation factor 2α (eIF2α). However, the overexpression of nsp2 or its TM domain significantly attenuated the mammalian target of rapamycin (mTOR) signaling pathway, an alternative pathway for modulating host gene expression. PRRSV infection also attenuated the mTOR signaling pathway, and PRRSV-induced host translation shutoff could be partly reversed when the attenuated mTOR phosphorylation was reactivated by an activator of the mTOR pathway. PRRSV infection still negatively regulated the host translation when the effects of eIF2α phosphorylation were completely reversed. Taken together, our results demonstrate that PRRSV infection induces host translation shutoff and that nsp2 is associated with this process. Both eIF2α phosphorylation and the attenuation of the mTOR signaling pathway contribute to PRRSV-induced host translation arrest. IMPORTANCE Viruses are obligate parasites, and the production of progeny viruses relies strictly on the host translation machinery. Therefore, the efficient modulation of host mRNA translation benefits viral replication, spread, and evolution. In this study, we provide evidence that porcine reproductive and respiratory syndrome virus (PRRSV) infection induces host translation shutoff and that the viral nonstructural protein nsp2 is associated with this process. Many viruses induce host translation shutoff by phosphorylating eukaryotic initiation factor 2α (eIF2α). However, PRRSV nsp2 does not induce eIF2α phosphorylation but attenuates the mTOR signaling pathway, another pathway regulating the host cell translational machinery. We also found that PRRSV-induced host translation shutoff was partly reversed by dephosphorylating eIF2α or reactivating the mTOR pathway, indicating that PRRSV infection induces both eIF2α-phosphorylation-dependent and -independent host translation shutoff. Copyright © 2018 American Society for Microbiology.

Environmental and ecological factors that shape the gut bacterial communities of fish: a meta-analysis

PubMed Central

Sullam, Karen E.; Essinger, Steven D.; Lozupone, Catherine A.; O’Connor, Michael P.; Rosen, Gail L.; Knight, Rob; Kilham, Susan S.; Russell, Jacob A.

2013-01-01

Symbiotic bacteria often help their hosts acquire nutrients from their diet, showing trends of co-evolution and independent acquisition by hosts from the same trophic levels. While these trends hint at important roles for biotic factors, the effects of the abiotic environment on symbiotic community composition remain comparably understudied. In this investigation, we examined the influence of abiotic and biotic factors on the gut bacterial communities of fish from different taxa, trophic levels and habitats. Phylogenetic and statistical analyses of 25 16S rRNA libraries revealed that salinity, trophic level and possibly host phylogeny shape the composition of fish gut bacteria. When analysed alongside bacterial communities from other environments, fish gut communities typically clustered with gut communities from mammals and insects. Similar consideration of individual phylotypes (vs. communities) revealed evolutionary ties between fish gut microbes and symbionts of animals, as many of the bacteria from the guts of herbivorous fish were closely related to those from mammals. Our results indicate that fish harbour more specialized gut communities than previously recognized. They also highlight a trend of convergent acquisition of similar bacterial communities by fish and mammals, raising the possibility that fish were the first to evolve symbioses resembling those found among extant gut fermenting mammals. PMID:22486918

Human Gastric Mucins Differently Regulate Helicobacter pylori Proliferation, Gene Expression and Interactions with Host Cells

PubMed Central

Skoog, Emma C.; Sjöling, Åsa; Navabi, Nazanin; Holgersson, Jan; Lundin, Samuel B.; Lindén, Sara K.

2012-01-01

Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host. PMID:22563496

Three-way interaction among plants, bacteria, and coleopteran insects.

PubMed

Wielkopolan, Beata; Obrępalska-Stęplowska, Aleksandra

2016-08-01

Coleoptera, the largest and the most diverse Insecta order, is characterized by multiple adaptations to plant feeding. Insect-associated microorganisms can be important mediators and modulators of interactions between insects and plants. Interactions between plants and insects are highly complex and involve multiple factors. There are various defense mechanisms initiated by plants upon attack by herbivorous insects, including the development of morphological structures and the synthesis of toxic secondary metabolites and volatiles. In turn, herbivores have adapted to feeding on plants and further sophisticated adaptations to overcome plant responses may continue to evolve. Herbivorous insects may detoxify toxic phytocompounds, sequester poisonous plant factors, and alter their own overall gene expression pattern. Moreover, insects are associated with microbes, which not only considerably affect insects, but can also modify plant defense responses to the benefit of their host. Plants are also frequently associated with endophytes, which may act as bioinsecticides. Therefore, it is very important to consider the factors influencing the interaction between plants and insects. Herbivorous insects cause considerable damage to global crop production. Coleoptera is the largest and the most diverse order in the class Insecta. In this review, various aspects of the interactions among insects, microbes, and plants are described with a focus on coleopteran species, their bacterial symbionts, and their plant hosts to demonstrate that many factors contribute to the success of coleopteran herbivory.

Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

PubMed

Amato, Katherine R

2016-01-01

The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. © 2016 Wiley Periodicals, Inc.

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

PubMed Central

Terasaki, Kaori; Ramirez, Sydney I.; Makino, Shinji

2016-01-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence. PMID:27711108

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence.

PubMed

Terasaki, Kaori; Ramirez, Sydney I; Makino, Shinji

2016-10-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.

Genome-Scale Analysis of Mycoplasma agalactiae Loci Involved in Interaction with Host Cells

PubMed Central

Skapski, Agnès; Hygonenq, Marie-Claude; Sagné, Eveline; Guiral, Sébastien; Citti, Christine; Baranowski, Eric

2011-01-01

Mycoplasma agalactiae is an important pathogen of small ruminants, in which it causes contagious agalactia. It belongs to a large group of “minimal bacteria” with a small genome and reduced metabolic capacities that are dependent on their host for nutrients. Mycoplasma survival thus relies on intimate contact with host cells, but little is known about the factors involved in these interactions or in the more general infectious process. To address this issue, an assay based on goat epithelial and fibroblastic cells was used to screen a M. agalactiae knockout mutant library. Mutants with reduced growth capacities in cell culture were selected and 62 genomic loci were identified as contributing to this phenotype. As expected for minimal bacteria, “transport and metabolism” was the functional category most commonly implicated in this phenotype, but 50% of the selected mutants were disrupted in coding sequences (CDSs) with unknown functions, with surface lipoproteins being most commonly represented in this category. Since mycoplasmas lack a cell wall, lipoproteins are likely to be important in interactions with the host. A few intergenic regions were also identified that may act as regulatory sequences under co-culture conditions. Interestingly, some mutants mapped to gene clusters that are highly conserved across mycoplasma species but located in different positions. One of these clusters was found in a transcriptionally active region of the M. agalactiae chromosome, downstream of a cryptic promoter. A possible scenario for the evolution of these loci is discussed. Finally, several CDSs identified here are conserved in other important pathogenic mycoplasmas, and some were involved in horizontal gene transfer with phylogenetically distant species. These results provide a basis for further deciphering functions mediating mycoplasma-host interactions. PMID:21966487

Environmental Variation Generates Environmental Opportunist Pathogen Outbreaks.

PubMed

Anttila, Jani; Kaitala, Veijo; Laakso, Jouni; Ruokolainen, Lasse

2015-01-01

Many socio-economically important pathogens persist and grow in the outside host environment and opportunistically invade host individuals. The environmental growth and opportunistic nature of these pathogens has received only little attention in epidemiology. Environmental reservoirs are, however, an important source of novel diseases. Thus, attempts to control these diseases require different approaches than in traditional epidemiology focusing on obligatory parasites. Conditions in the outside-host environment are prone to fluctuate over time. This variation is a potentially important driver of epidemiological dynamics and affect the evolution of novel diseases. Using a modelling approach combining the traditional SIRS models to environmental opportunist pathogens and environmental variability, we show that epidemiological dynamics of opportunist diseases are profoundly driven by the quality of environmental variability, such as the long-term predictability and magnitude of fluctuations. When comparing periodic and stochastic environmental factors, for a given variance, stochastic variation is more likely to cause outbreaks than periodic variation. This is due to the extreme values being further away from the mean. Moreover, the effects of variability depend on the underlying biology of the epidemiological system, and which part of the system is being affected. Variation in host susceptibility leads to more severe pathogen outbreaks than variation in pathogen growth rate in the environment. Positive correlation in variation on both targets can cancel the effect of variation altogether. Moreover, the severity of outbreaks is significantly reduced by increase in the duration of immunity. Uncovering these issues helps in understanding and controlling diseases caused by environmental pathogens.

A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.

PubMed

Yu, Qilin; Dong, Yijie; Xu, Ning; Qian, Kefan; Chen, Yulu; Zhang, Biao; Xing, Laijun; Li, Mingchun

2014-11-01

Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

PubMed Central

Gjini, Erida; Brito, Patricia H.

2016-01-01

Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes. PMID:27078624

Within-host evolution versus immigration as a determinant of Escherichia coli diversity in the human gastrointestinal tract.

PubMed

Dixit, Ojas V A; O'Brien, Claire L; Pavli, Paul; Gordon, David M

2018-03-01

When a human host harbors two or more strains of Escherichia coli, the second strain is more likely to be a member of the same phylogroup rather than a different phylogroup. This outcome may be the consequence of a within host evolution event or an independent immigration/establishment event. To determine the relative importance of these two events in determining E. coli diversity in a host, a collection of multiple E. coli isolates recovered from each of 67 patients undergoing colonoscopies was used. Whole genome sequence data were available for one example of every REP-fingerprint type identified in a patient. Sequence type (ST) and single-nucleotide polymorphism (SNP) analyses revealed that 83% of strains observed in the host population were a consequence of immigration/establishment events. Restricting the analysis to hosts harboring two or more strains belonging to the same phylogroup revealed that in about half of these cases, the presence of a second strain belonging to the same phylogroup was the consequence of an independent immigration/establishment event. Thus, the results of this study show that despite hosts being exposed to a diversity of E. coli via their food, factors related to the host also determine what E. coli strains succeed in establishing. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Quantification of Hepatitis C Virus Cell-to-Cell Spread Using a Stochastic Modeling Approach

PubMed Central

Martin, Danyelle N.; Perelson, Alan S.; Dahari, Harel

2015-01-01

ABSTRACT It has been proposed that viral cell-to-cell transmission plays a role in establishing and maintaining chronic infections. Thus, understanding the mechanisms and kinetics of cell-to-cell spread is fundamental to elucidating the dynamics of infection and may provide insight into factors that determine chronicity. Because hepatitis C virus (HCV) spreads from cell to cell and has a chronicity rate of up to 80% in exposed individuals, we examined the dynamics of HCV cell-to-cell spread in vitro and quantified the effect of inhibiting individual host factors. Using a multidisciplinary approach, we performed HCV spread assays and assessed the appropriateness of different stochastic models for describing HCV focus expansion. To evaluate the effect of blocking specific host cell factors on HCV cell-to-cell transmission, assays were performed in the presence of blocking antibodies and/or small-molecule inhibitors targeting different cellular HCV entry factors. In all experiments, HCV-positive cells were identified by immunohistochemical staining and the number of HCV-positive cells per focus was assessed to determine focus size. We found that HCV focus expansion can best be explained by mathematical models assuming focus size-dependent growth. Consistent with previous reports suggesting that some factors impact HCV cell-to-cell spread to different extents, modeling results estimate a hierarchy of efficacies for blocking HCV cell-to-cell spread when targeting different host factors (e.g., CLDN1 > NPC1L1 > TfR1). This approach can be adapted to describe focus expansion dynamics under a variety of experimental conditions as a means to quantify cell-to-cell transmission and assess the impact of cellular factors, viral factors, and antivirals. IMPORTANCE The ability of viruses to efficiently spread by direct cell-to-cell transmission is thought to play an important role in the establishment and maintenance of viral persistence. As such, elucidating the dynamics of cell-to-cell spread and quantifying the effect of blocking the factors involved has important implications for the design of potent antiviral strategies and controlling viral escape. Mathematical modeling has been widely used to understand HCV infection dynamics and treatment response; however, these models typically assume only cell-free virus infection mechanisms. Here, we used stochastic models describing focus expansion as a means to understand and quantify the dynamics of HCV cell-to-cell spread in vitro and determined the degree to which cell-to-cell spread is reduced when individual HCV entry factors are blocked. The results demonstrate the ability of this approach to recapitulate and quantify cell-to-cell transmission, as well as the impact of specific factors and potential antivirals. PMID:25833046

A method to quantify infection and colonization of holm oak (Quercus ilex) roots by Phytophthora cinnamomi

PubMed Central

2012-01-01

Phytophthora cinnamomi Rands. is an important root rot pathogen widely distributed in the north hemisphere, with a large host range. Among others diseases, it is known to be a principal factor in the decline of holm oak and cork oak, the most important tree species in the “dehesa” ecosystem of south-western Spain. Previously, the focus of studies on P. cinnamomi and holm oak have been on molecular tools for identification, functional responses of the host, together with other physiological and morphological host variables. However, a microscopic index to describe the degree of infection and colonization in the plant tissues has not yet been developed. A colonization or infection index would be a useful tool for studies that examine differences between individuals subjected to different treatments or to individuals belonging to different breeding accessions, together with their specific responses to the pathogen. This work presents a methodology based on the capture and digital treatment of microscopic images, using simple and accessible software, together with a range of variables that quantify the infection and colonization process. PMID:22974221

Indication for Co-evolution of Lactobacillus johnsonii with its hosts

PubMed Central

2012-01-01

Background The intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts. Results A wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice. Conclusions Our typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria. PMID:22827843

Indication for Co-evolution of Lactobacillus johnsonii with its hosts.

PubMed

Buhnik-Rosenblau, Keren; Matsko-Efimov, Vera; Jung, Minju; Shin, Heuynkil; Danin-Poleg, Yael; Kashi, Yechezkel

2012-07-25

The intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts. A wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice. Our typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria.

The CXCL12/CXCR4 Signaling Pathway: A New Susceptibility Factor in Human Papillomavirus Pathogenesis

PubMed Central

Meuris, Floriane; Carthagena, Laetitia; Cutolo, Pasquale; Xue, Yuezhen; Thierry, Françoise; Doorbar, John; Bachelerie, Françoise

2016-01-01

The productive human papillomavirus (HPV) life cycle is tightly linked to the differentiation and cycling of keratinocytes. Deregulation of these processes and stimulation of cell proliferation by the action of viral oncoproteins and host cell factors underlies HPV-mediated carcinogenesis. Severe HPV infections characterize the wart, hypogammaglobulinemia, infection, and myelokathexis (WHIM) immunodeficiency syndrome, which is caused by gain-of-function mutations in the CXCR4 receptor for the CXCL12 chemokine, one of which is CXCR41013. We investigated whether CXCR41013 interferes in the HPV18 life cycle in epithelial organotypic cultures. Expression of CXCR41013 promoted stabilization of HPV oncoproteins, thus disturbing cell cycle progression and proliferation at the expense of the ordered expression of the viral genes required for virus production. Conversely, blocking CXCR41013 function restored virus production and limited HPV-induced carcinogenesis. Thus, CXCR4 and its potential activation by genetic alterations in the course of the carcinogenic process can be considered as an important host factor for HPV carcinogenesis. PMID:27918748

Interactions Between the Intestinal Microbiome and Liver Diseases

PubMed Central

Schnabl, Bernd; Brenner, David A.

2014-01-01

The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

Impact of Host Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive Systematic Review and Meta-analysis.

PubMed

Cacciamani, Giovanni; Gill, Tania S; Medina, Luis; Ashrafi, Akbar; Winter, Matthew; Sotelo, Renè; Artibani, Walter; Gill, Inderbir

2018-05-03

Host factors (tumor size/complexity, patient comorbidities) impact outcomes of robotic partial nephrectomy (RPN). We report a comprehensive systematic review and meta-analysis to critically evaluate impact of host factors on operative, peri-operative, functional, oncological and survival outcomes of RPN. All full-text English-language publications on RPN comparing host factors were evaluated. We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement and Agency for Healthcare Research and Quality (AHRQ) guidelines to evaluate Pubmed®, Scopus® and Web of Science® (01/01/2000-31/06/2017). Weighted mean difference (WMD) and odds ratio (OR) compared continuous and dichotomous variables, respectively. Sensitivity analyses were performed as needed. To condense the sheer volume of analyses, data are presented using novel summary forest plots. PROSPERO registration number CRD42017062712. Our meta-analysis evaluated 41 papers including 10,506 patients. Tumor factors: Compared to patients with complex tumors, those with non-complex tumors had lesser OR-time (WMD: -44.95; p=0.003), EBL (WMD: -160; p< 0.003), warm ischemia time (WIT) (WMD:-8.56 ; p≤ 0.00001) and post-operative complications (OR:0.42; p=0.01). Tumors > 4 cm were associated with higher OR-time (WMD: 30.11; p≤ 0.00001), EBL (WMD: 39.26, 95% CI 28.77, 49.74; p≤ 0.00001), WIT (WMD: 5.17; p≤ 0.00001), transfusions (OR: 3.15; p=0.003), postoperative complications (OR:1.88; p=0.004) and LOS (WMD:0.56; p=0.0004). Hilar tumors reported greater EBL (WMD:51.34; p=0.03), WIT (WMD: 8.17; p≤ 0.00001) and conversion to OPN (OR: 14.14; p=0.006). Tumor location, anterior versus posterior, did not impact RPN outcomes. Patient factors: Older patients (> 70 years) trended non-significantly towards greater %eGFR decrease and overall mortality. Abnormal BMI cohort reported greater OR-time (WMD:13.47; p<0.001), EBL(WMD:45.44; p<0.0001) and postoperative complications (OR:1.48; p=0.03). CKD cohort had lesser reduction in post-operative % eGFR (WMD:7.16; 95% CI 2.74, 11.59; p=0.002) and increased postoperative complications (OR: 2.05; 95% CI 1.47, 2.85). RPN outcomes are impacted by host factors, including tumor and patient characteristics. Awareness of this increased risk, and its mitigation with expert patient selection, is important for excellent RPN outcomes. Our meta-analysis provides comprehensive, objective, summary data of 10,506 patients, detailing discreet outcomes for discreet host factors, to better inform urologists and patients considering RPN surgery. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

PubMed

Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

2013-01-15

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Yersinia pestis targets neutrophils via complement receptor 3

PubMed Central

Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

2015-01-01

Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

Importance of phoresy in the transmission of Acarina.

PubMed

Macchioni, F

2007-06-01

Dispersal capacity plays a central role in the radiation of animals, facilitating the exploitation of habitats variously distributed in space or in time or both. Many living species are unable to leave a host, crawl around, and find a new host, so they must rely on external factors to be transmitted. Biotical factors may be important in passive transport and the process, by means of which an animal is passively transported by a selected carrier of different species, is known as "phoresy". Phoresy is a phenomenon in which one animal (the phoretic) seeks out and attaches to an animal of another species, with which it does not share any phase of the life cycle, for dispersal, during which time the phoretic animal becomes quiescent, stopping feeding and development. Activity starts again beginning with detachment, induced by stimuli originating from its carrier or the microhabitat. The adaptive traits of phoresy may be categorized as follow: host surface, quiescence, recognition of signals to abandon the carrier and, if needed, synchronization with the host life cycle. Phoresy is exploited by many Arthropods. In Acarina, there are basically four main types of phoresy. First, there is a type in which adult females are the only forms becoming phoretic and attachment is by means of chelicerae, palpal hooks and ambulacral claws, which grasp a seta or a fold of the integument of carrier-host. The second type is represented by mites, in which deutonymphs are phoretic; there is generally no cheliceral or sucker attachment in this group, mites instead hanging on by their ambulacral claws. The third type is similar to the second in that deutonymphs are phoretic; however, in this case, attachment to the host is by means of an anal pedicel formed by a substance, extruded through the anus, which hardens upon coming in contact with air and literally glues the mite to its host. In the fourth type there is a very highly modified deutonymph stage, called hypope, which only occurs at certain times, presumably when environmental conditions are no longer appropriate for the mite. Hypope is simplified morphologically, may have many sucker-like discs or claspers for efficient attachment, and is much more resistant to desiccation than are other stages of the life cycle.

Host genetic determinants of HIV pathogenesis: an immunologic perspective.

PubMed

Hunt, Peter W; Carrington, Mary

2008-05-01

The purpose of this review is to highlight recent advances in our understanding of host genetic determinants of HIV pathogenesis and to provide a theoretical framework for interpreting these studies in the context of our evolving understanding of HIV immunopathogenesis. The first genome-wide association analysis of host determinants of HIV pathogenesis and other recent studies evaluating the interaction between killer cell immunoglobulin-like receptors and human leukocyte antigen alleles have implicated both adaptive and innate immune responses in the control of HIV replication. Furthermore, genetic variation associated with the expression of CCR5 and its ligand have been strongly associated with both decreased susceptibility to HIV infection and delayed clinical progression, independent of their effects on viral replication, suggesting a potential role for CCR5 inhibitors as immune-based therapies in HIV disease. Host factors associated with the control of HIV replication may help identify important targets for vaccine design, while those associated with delayed clinical progression provide targets for future immune-based therapies against HIV infection.

Dual functions of Rift Valley fever virus NSs protein: inhibition of host mRNA transcription and post-transcriptional downregulation of protein kinase PKR.

PubMed

Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

2009-09-01

Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis, or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-beta mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase (PKR), to prevent phosphorylation of eIF2alpha and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts.

Environment and host as large-scale controls of ectomycorrhizal fungi.

PubMed

van der Linde, Sietse; Suz, Laura M; Orme, C David L; Cox, Filipa; Andreae, Henning; Asi, Endla; Atkinson, Bonnie; Benham, Sue; Carroll, Christopher; Cools, Nathalie; De Vos, Bruno; Dietrich, Hans-Peter; Eichhorn, Johannes; Gehrmann, Joachim; Grebenc, Tine; Gweon, Hyun S; Hansen, Karin; Jacob, Frank; Kristöfel, Ferdinand; Lech, Paweł; Manninger, Miklós; Martin, Jan; Meesenburg, Henning; Merilä, Päivi; Nicolas, Manuel; Pavlenda, Pavel; Rautio, Pasi; Schaub, Marcus; Schröck, Hans-Werner; Seidling, Walter; Šrámek, Vít; Thimonier, Anne; Thomsen, Iben Margrete; Titeux, Hugues; Vanguelova, Elena; Verstraeten, Arne; Vesterdal, Lars; Waldner, Peter; Wijk, Sture; Zhang, Yuxin; Žlindra, Daniel; Bidartondo, Martin I

2018-06-06

Explaining the large-scale diversity of soil organisms that drive biogeochemical processes-and their responses to environmental change-is critical. However, identifying consistent drivers of belowground diversity and abundance for some soil organisms at large spatial scales remains problematic. Here we investigate a major guild, the ectomycorrhizal fungi, across European forests at a spatial scale and resolution that is-to our knowledge-unprecedented, to explore key biotic and abiotic predictors of ectomycorrhizal diversity and to identify dominant responses and thresholds for change across complex environmental gradients. We show the effect of 38 host, environment, climate and geographical variables on ectomycorrhizal diversity, and define thresholds of community change for key variables. We quantify host specificity and reveal plasticity in functional traits involved in soil foraging across gradients. We conclude that environmental and host factors explain most of the variation in ectomycorrhizal diversity, that the environmental thresholds used as major ecosystem assessment tools need adjustment and that the importance of belowground specificity and plasticity has previously been underappreciated.

Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes

PubMed Central

HAMADA, Shigeyuki; KAWABATA, Shigetada; NAKAGAWA, Ichiro

2015-01-01

Group A streptococcus (GAS) or Streptococcus pyogenes causes various diseases ranging from self-limiting sore throat to deadly invasive diseases. The genome size of GAS is 1.85–1.9 Mb, and genomic rearrangement has been demonstrated. GAS possesses various surface-associated substances such as hyaluronic capsule, M proteins, and fibronectin/laminin/immunoglobulin-binding proteins. These are related to the virulence and play multifaceted and mutually reflected roles in the pathogenesis of GAS infections. Invasion of GAS into epithelial cells and deeper tissues provokes immune and non-immune defense or inflammatory responses including the recruitment of neutrophils, macrophages, and dendritic cells in hosts. GAS frequently evades host defense mechanisms by using its virulence factors. Extracellular products of GAS may perturb cellular and subcellular functions and degrade tissues enzymatically, which leads to the aggravation of local and/or systemic disorders in the host. In this review, we summarize some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these. PMID:26666305

Dual Functions of Rift Valley Fever Virus NSs Protein: Inhibition of Host mRNA Transcription and Post-transcriptional Downregulation of Protein Kinase PKR

PubMed Central

Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C. J.; Makino, Shinji

2011-01-01

Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-β mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase, PKR, to prevent phosphorylation of eIF2α and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts. PMID:19751406

Utilization of human DC-SIGN and L-SIGN for entry and infection of host cells by the New World arenavirus, Junín virus

PubMed Central

Belouzard, Sandrine; Cordo, Sandra M.; Candurra, Nélida A.; Whittaker, Gary R.

2014-01-01

The target cell tropism of enveloped viruses is regulated by interactions between viral proteins and cellular receptors determining susceptibility at a host cell, tissue or species level. However, a number of additional cell-surface moieties can also bind viral envelope glycoproteins and could act as capture receptors, serving as attachment factors to concentrate virus particles on the cell surface, or to disseminate the virus infection to target organs or susceptible cells within the host. Here, we used Junín virus (JUNV) or JUNV glycoprotein complex (GPC)-pseudotyped particles to study their ability to be internalized by the human C-type lectins hDC- or hL-SIGN. Our results provide evidence that hDC- and hL-SIGN can mediate the entry of Junín virus into cells, and may play an important role in virus infection and dissemination in the host. PMID:24183720

Effects of antibiotic resistance (AR) and microbiota shifts on Campylobacter jejuni-mediated diseases.

PubMed

Brooks, Phillip T; Mansfield, Linda S

2017-12-01

Campylobacter jejuni is an important zoonotic pathogen recently designated a serious antimicrobial resistant (AR) threat. While most patients with C. jejuni experience hemorrhagic colitis, serious autoimmune conditions can follow including inflammatory bowel disease (IBD) and the acute neuropathy Guillain Barré Syndrome (GBS). This review examines inter-relationships among factors mediating C. jejuni diarrheal versus autoimmune disease especially AR C. jejuni and microbiome shifts. Because both susceptible and AR C. jejuni are acquired from animals or their products, we consider their role in harboring strains. Inter-relationships among factors mediating C. jejuni colonization, diarrheal and autoimmune disease include C. jejuni virulence factors and AR, the enteric microbiome, and host responses. Because AR C. jejuni have been suggested to affect the severity of disease, length of infections and propensity to develop GBS, it is important to understand how these interactions occur when strains are under selection by antimicrobials. More work is needed to elucidate host-pathogen interactions of AR C. jejuni compared with susceptible strains and how AR C. jejuni are maintained and evolve in animal reservoirs and the extent of transmission to humans. These knowledge gaps impair the development of effective strategies to prevent the emergence of AR C. jejuni in reservoir species and human populations.

Dengue Virus Subverts Host Innate Immunity by Targeting Adaptor Protein MAVS

PubMed Central

He, Zhenjian; Zhu, Xun; Wen, Weitao; Yuan, Jie; Hu, Yiwen; Chen, Jiahui; An, Shu; Dong, Xinhuai; Lin, Cuiji; Yu, Jianchen; Wu, Jueheng; Yang, Yi; Cai, Junchao; Li, Jun

2016-01-01

ABSTRACT Dengue virus (DENV) is the most common mosquito-borne virus infecting humans and is currently a serious global health challenge. To establish infection in its host cells, DENV must subvert the production and/or antiviral effects of interferon (IFN). The aim of this study was to understand the mechanisms by which DENV suppresses IFN production. We determined that DENV NS4A interacts with mitochondrial antiviral signaling protein (MAVS), which was previously found to activate NF-κB and IFN regulatory factor 3 (IRF3), thus inducing type I IFN in the mitochondrion-associated endoplasmic reticulum membranes (MAMs). We further demonstrated that NS4A is associated with the N-terminal CARD-like (CL) domain and the C-terminal transmembrane (TM) domain of MAVS. This association prevented the binding of MAVS to RIG-I, resulting in the repression of RIG-I-induced IRF3 activation and, consequently, the abrogation of IFN production. Collectively, our findings illustrate a new molecular mechanism by which DENV evades the host immune system and suggest new targets for anti-DENV strategies. IMPORTANCE Type I interferon (IFN) constitutes the first line of host defense against invading viruses. To successfully establish infection, dengue virus (DENV) must counteract either the production or the function of IFN. The mechanism by which DENV suppresses IFN production is poorly understood and characterized. In this study, we demonstrate that the DENV NS4A protein plays an important role in suppressing interferon production through binding MAVS and disrupting the RIG-I–MAVS interaction in mitochondrion-associated endoplasmic reticulum membranes (MAMs). Our study reveals that MAVS is a novel host target of NS4A and provides a molecular mechanism for DENV evasion of the host innate immune response. These findings have important implications for understanding the pathogenesis of DENV and may provide new insights into using NS4A as a therapeutic and/or prevention target. PMID:27252539

Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus.

PubMed

Child, Stephanie J; Hickson, Sarah E; Bayer, Avraham; Malouli, Daniel; Früh, Klaus; Geballe, Adam P

2018-03-15

While cytomegalovirus (CMV) infections are often limited in host range by lengthy coevolution with a single host species, a few CMVs are known to deviate from this rule. For example, rhesus macaque CMV (RhCMV), a model for human CMV (HCMV) pathogenesis and vaccine development, can replicate in human cells, as well as in rhesus cells. Both HCMV and RhCMV encode species-specific antagonists of the broadly acting host cell restriction factor protein kinase R (PKR). Although the RhCMV antagonist of PKR, rTRS1, has very limited activity against human PKR, here, we show it is essential for RhCMV replication in human cells because it prevents human PKR from phosphorylating the translation initiation factor eIF2α, thereby allowing continued translation and viral replication. Although rTRS1 is necessary for RhCMV replication, it is not sufficient to rescue replication of HCMV lacking its own PKR antagonists in human fibroblasts. However, overexpression of rTRS1 in human fibroblasts enabled HCMV expressing rTRS1 to replicate, indicating that elevated levels or early expression of a weak antagonist can counteract a resistant restriction factor like human PKR. Exploring potential mechanisms that might allow RhCMV to replicate in human cells revealed that RhCMV makes no less double-stranded RNA than HCMV. Rather, in human cells, RhCMV expresses rTRS1 at levels 2 to 3 times higher than those of the HCMV-encoded PKR antagonists during HCMV infection. These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells. IMPORTANCE Rhesus macaque cytomegalovirus (RhCMV) offers a valuable model for studying congenital human cytomegalovirus (HCMV) pathogenesis and vaccine development. Therefore, it is critical to understand variations in how each virus infects and affects its host species to be able to apply insights gained from the RhCMV model to HCMV. While HCMV is capable only of infecting cells from humans and very closely related species, RhCMV displays a wider host range, including human as well as rhesus cells. RhCMV expresses an antagonist of a broadly acting antiviral factor present in all mammalian cells, and its ability to counter both the rhesus and human versions of this host factor is a key component of RhCMV's ability to cross species barriers. Here, we examine the molecular mechanisms that allow this RhCMV antagonist to function against a human restriction factor. Copyright © 2018 American Society for Microbiology.

Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health.

PubMed

Wasielewski, Helen; Alcock, Joe; Aktipis, Athena

2016-05-01

Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Phytophthora capsici-tomato interaction features dramatic shifts in gene expression associated with a hemi-biotrophic lifestyle.

PubMed

Jupe, Julietta; Stam, Remco; Howden, Andrew J M; Morris, Jenny A; Zhang, Runxuan; Hedley, Pete E; Huitema, Edgar

2013-06-25

Plant-microbe interactions feature complex signal interplay between pathogens and their hosts. Phytophthora species comprise a destructive group of fungus-like plant pathogens, collectively affecting a wide range of plants important to agriculture and natural ecosystems. Despite the availability of genome sequences of both hosts and microbes, little is known about the signal interplay between them during infection. In particular, accurate descriptions of coordinate relationships between host and microbe transcriptional programs are lacking. Here, we explore the molecular interaction between the hemi-biotrophic broad host range pathogen Phytophthora capsici and tomato. Infection assays and use of a composite microarray allowed us to unveil distinct changes in both P. capsici and tomato transcriptomes, associated with biotrophy and the subsequent switch to necrotrophy. These included two distinct transcriptional changes associated with early infection and the biotrophy to necrotrophy transition that may contribute to infection and completion of the P. capsici lifecycle Our results suggest dynamic but highly regulated transcriptional programming in both host and pathogen that underpin P. capsici disease and hemi-biotrophy. Dynamic expression changes of both effector-coding genes and host factors involved in immunity, suggests modulation of host immune signaling by both host and pathogen. With new unprecedented detail on transcriptional reprogramming, we can now explore the coordinate relationships that drive host-microbe interactions and the basic processes that underpin pathogen lifestyles. Deliberate alteration of lifestyle-associated transcriptional changes may allow prevention or perhaps disruption of hemi-biotrophic disease cycles and limit damage caused by epidemics.

Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.

PubMed

Martínez, Inés; Perdicaro, Diahann J; Brown, Andrew W; Hammons, Susan; Carden, Trevor J; Carr, Timothy P; Eskridge, Kent M; Walter, Jens

2013-01-01

The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.

Influence of the Host Contact Sequence on the Outcome of Competition among Aspergillus flavus Isolates during Host Tissue Invasion▿

PubMed Central

Mehl, H. L.; Cotty, P. J.

2011-01-01

Biological control of aflatoxin contamination by Aspergillus flavus is achieved through competitive exclusion of aflatoxin producers by atoxigenic strains. Factors dictating the extent to which competitive displacement occurs during host infection are unknown. The role of initial host contact in competition between pairs of A. flavus isolates coinfecting maize kernels was examined. Isolate success during tissue invasion and reproduction was assessed by quantification of isolate-specific single nucleotide polymorphisms using pyrosequencing. Isolates were inoculated either simultaneously or 1 h apart. Increased success during competition was conferred to the first isolate to contact the host independent of that isolate's innate competitive ability. The first-isolate advantage decreased with the conidial concentration, suggesting capture of limited resources on kernel surfaces contributes to competitive exclusion. Attempts to modify access to putative attachment sites by either coating kernels with dead conidia or washing kernels with solvents did not influence the success of the first isolate, suggesting competition for limited attachment sites on kernel surfaces does not mediate first-isolate advantage. The current study is the first to demonstrate an immediate competitive advantage conferred to A. flavus isolates upon host contact and prior to either germ tube emergence or host colonization. This suggests the timing of host contact is as important to competition during disease cycles as innate competitive ability. Early dispersal to susceptible crop components may allow maintenance within A. flavus populations of genetic types with low competitive ability during host tissue invasion. PMID:21216896

Are parasite richness and abundance linked to prey species richness and individual feeding preferences in fish hosts?

PubMed

Cirtwill, Alyssa R; Stouffer, Daniel B; Poulin, Robert; Lagrue, Clément

2016-01-01

Variations in levels of parasitism among individuals in a population of hosts underpin the importance of parasites as an evolutionary or ecological force. Factors influencing parasite richness (number of parasite species) and load (abundance and biomass) at the individual host level ultimately form the basis of parasite infection patterns. In fish, diet range (number of prey taxa consumed) and prey selectivity (proportion of a particular prey taxon in the diet) have been shown to influence parasite infection levels. However, fish diet is most often characterized at the species or fish population level, thus ignoring variation among conspecific individuals and its potential effects on infection patterns among individuals. Here, we examined parasite infections and stomach contents of New Zealand freshwater fish at the individual level. We tested for potential links between the richness, abundance and biomass of helminth parasites and the diet range and prey selectivity of individual fish hosts. There was no obvious link between individual fish host diet and helminth infection levels. Our results were consistent across multiple fish host and parasite species and contrast with those of earlier studies in which fish diet and parasite infection were linked, hinting at a true disconnect between host diet and measures of parasite infections in our study systems. This absence of relationship between host diet and infection levels may be due to the relatively low richness of freshwater helminth parasites in New Zealand and high host-parasite specificity.

Chlamydia trachomatis can protect host cells against apoptosis in the absence of cellular Inhibitor of Apoptosis Proteins and Mcl-1.

PubMed

Ying, Songmin; Christian, Jan G; Paschen, Stefan A; Häcker, Georg

2008-01-01

Infection with Chlamydia protects mammalian host cells against apoptosis. Hypotheses have been proposed to explain this molecularly, including the up-regulation of host anti-apoptotic proteins such as cellular Inhibitor of Apoptosis Protein (IAP) 2 and the Bcl-2 protein Mcl-1. To test for the importance of these proteins, we used mouse embryonic fibroblasts from gene-targeted mice that were deficient in cIAP1, cIAP2, cIAP1/cIAP2, XIAP, or Mcl-1. Infection with Chlamydia trachomatis protected all cells equally well against apoptosis, which was induced either with tumour necrosis factor/cycloheximide (IAP-knock-out cells) or staurosporine (Mcl-1-knock-out). Therefore, these cellular anti-apoptotic proteins are not essential for apoptosis-protection by C. trachomatis.

Linkages of Weather and Climate With Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), Enzootic Transmission of Borrelia burgdorferi, and Lyme Disease in North America.

PubMed

Eisen, Rebecca J; Eisen, Lars; Ogden, Nicholas H; Beard, Charles B

2016-03-01

Lyme disease has increased both in incidence and geographic extent in the United States and Canada over the past two decades. One of the underlying causes is changes during the same time period in the distribution and abundance of the primary vectors: Ixodes scapularis Say and Ixodes pacificus Cooley and Kohls in eastern and western North America, respectively. Aside from short periods of time when they are feeding on hosts, these ticks exist in the environment where temperature and relative humidity directly affect their development, survival, and host-seeking behavior. Other important factors that strongly influence tick abundance as well as the proportion of ticks infected with the Lyme disease spirochete, Borrelia burgdorferi, include the abundance of hosts for the ticks and the capacity of tick hosts to serve as B. burgdorferi reservoirs. Here, we explore the linkages between climate variation and: 1) duration of the seasonal period and the timing of peak activity; 2) geographic tick distributions and local abundance; 3) enzootic B. burgdorferi transmission cycles; and 4) Lyme disease cases. We conclude that meteorological variables are most influential in determining host-seeking phenology and development, but, while remaining important cofactors, additional variables become critical when exploring geographic distribution and local abundance of ticks, enzootic transmission of B. burgdorferi, and Lyme disease case occurrence. Finally, we review climate change-driven projections for future impact on vector ticks and Lyme disease and discuss knowledge gaps and research needs.

Environmental and individual determinants of parasite richness across seasons in a free-ranging population of Mandrills (Mandrillus sphinx).

PubMed

Poirotte, Clémence; Basset, Didier; Willaume, Eric; Makaba, Fred; Kappeler, Peter M; Charpentier, Marie J E

2016-03-01

Parasites are ubiquitous and evolve fast. Therefore, they represent major selective forces acting on their hosts by influencing many aspects of their biology. Humans are no exception, as they share many parasites with animals and some of the most important outbreaks come from primates. While it appears important to understand the factors involved in parasite dynamics, we still lack a clear understanding of the determinants underlying parasitism. In this 2-year study, we identified several factors that influence parasite patterns in a wild population of free-ranging mandrills (Mandrillus sphinx). We explored the potential impact of seasonal factors-rainfall and temperature-and host characteristics, including sex, age, rank, and reproductive status, on parasite richness. We analyzed 12 parasite taxa found in 870 fecal samples collected from 63 individuals. Because nematodes and protozoa have different life-cycles, we analyzed these two types of parasites separately. Contrary to other studies where humid conditions seem favorable to parasite development, we report here that rainfall and high temperatures were associated with lower nematode richness and were not associated with lower protozoa richness. In contrast, female reproductive status seemed to reflect the seasonal patterns found for protozoa richness, as early gestating females harbored more protozoa than other females. Sex and dominance rank had no impact on overall parasite richness. However, age was associated with a specific decrease in nematode richness. Our study emphasizes the need to consider the ecological context, such as climatic conditions and habitat type, as well as the biology of both parasite and host when analyzing determinants of parasite richness. © 2015 Wiley Periodicals, Inc.

Candida glabrata: an emerging oral opportunistic pathogen.

PubMed

Li, L; Redding, S; Dongari-Bagtzoglou, A

2007-03-01

Following the widespread use of immunosuppressive therapy and broad-spectrum antimycotic prophylaxis, C. glabrata has emerged as an important opportunistic pathogen in the oral mucosa. In the past, studies on the virulence factors and host-pathogen interactions of this organism were scarce, but continued to rise in recent years. Denture-wearing, immunosuppression, antibiotic therapy, and aging are risk factors for oral colonization or infection with C. glabrata. Compared with C. albicans, C. glabrata exhibits lower oral keratinocyte-adherence capacity, but higher denture-surface-adherence ability. The role of extracellular hydrolase production in the virulence of this organism does not appear to be as important as it is in C. albicans pathogenesis. Although traditionally thought of as a non-transforming yeast organism, both phenotypic switching and pseudohyphal formation have recently been identified in C. glabrata, but their role in pathogenesis is not known. With the exception of granulocyte monocyte colony-stimulating factor, C. glabrata triggers a lower proinflammatory cytokine response in oral epithelial cells than does C. albicans, in a strain-dependent manner. C. glabrata is less susceptible to killing by human beta-defensins than is C. albicans and exhibits various degrees of resistance to the antifungal activity of salivary histatins and mucins. In addition, C. glabrata possesses both innate and acquired resistance against antifungal drugs, due to its ability to modify ergosterol biosynthesis, mitochondrial function, or antifungal efflux. This resistance allows for its relative overgrowth over other susceptible species and may contribute to the recent emergence of C. glabrata infections in chronically immunocompromised populations. Further investigations on the virulence and host-pathogen interactions of C. glabrata are needed to better define the pathogenesis of oral C. glabrata infection in susceptible hosts.

Seroprevalence and risk factors associated with exposure of water buffalo (Bubalus bubalis) to Neospora caninum in northeast Thailand.

PubMed

Kengradomkij, Chanya; Inpankaew, Tawin; Kamyingkird, Ketsarin; Wongpanit, Kannika; Wongnakphet, Sirichai; Mitchell, Thomas J; Xuan, Xuenan; Igarashi, Ikuo; Jittapalapong, Sathaporn; Stich, Roger W

2015-01-15

Water buffalo are important draft animals for agriculture in resource-restricted areas worldwide. Water buffalo were shown to be experimentally susceptible to infection with Neospora caninum, potentially affected by neosporosis, and naturally exposed to the parasite in Asia. Although enzootic to Thailand, the distribution of N. caninum among Thai water buffalo is unclear. The objectives of this study were to determine the seroprevalence of N. caninum among water buffalo of northeast Thailand and to identify risk factors associated with their exposure to N. caninum. Sera from 628 water buffalo from 288 farms were tested with an indirect fluorescent antibody test (IFAT). A total of 57 samples from 48 herds contained antibodies to N. caninum, indicating overall seroprevalence of 9.1% and 16.7% among individual animals and herds, respectively. The overall seroprevalence was highest in provinces located in the Khorat Basin in the southern part of the region tested. Host age was also associated with seroprevalence, with the greatest seroprevalence (16.1%) among buffalo over 10 years of age, followed by 5-10 years of age (13.4%), 3-5 years (9.2%), and less than 3 years (1.2%). These results collectively suggested that horizontal transmission from canine definitive hosts was an important route of water buffalo exposure to N. caninum. These results also verified the importance of risk factor analysis for effective bovine neosporosis control strategies at the local level. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of Habitat Conditions and Plant Traits on Leaf Damage in the Carduoideae Subfamily

PubMed Central

Münzbergová, Zuzana; Skuhrovec, Jiří

2013-01-01

Plant traits are the key factors that determine herbivore foraging selection. The traits serving as defense traits against herbivores represent a wide range of traits, such as chemical, physiological, morphological and life-history traits. While many studies considered plant defense traits at the within-species scale, much less is known from comparisons of a wide range of closely related species. The aim of this study was to identify factors responsible for the intensity of leaf damage in the Carduoideae subfamily of Asteraceae, which hosts many invasive species and thus is potential candidate plant species that could be controlled by biological control. Specifically, we wanted to see the relative importance of habitat characteristics, plant size and plants traits in determining the degree of folivory. The study identified several defense traits able to explain differences in herbivory between species after accounting for differences in the habitats in which the species occur and the plant size. Specifically, the most important traits were traits related to the quality of the leaf tissue expressed as the content of phosphorus, water and specific leaf area, which suggests that the leaf quality had a more important effect on the degree of herbivory than the presence of specific defense mechanisms such as spines and hair. Leaf quality is thus a candidate factor that drives herbivore choice when selecting which plant to feed on and should be considered when assessing the danger that a herbivore will switch hosts when introduced to a new range. PMID:23717643

Kaposi's Sarcoma-Associated Herpesvirus G-Protein-Coupled Receptor Prevents AU-Rich-Element-Mediated mRNA Decay

PubMed Central

Corcoran, Jennifer A.; Khaperskyy, Denys A.; Johnston, Benjamin P.; King, Christine A.; Cyr, David P.; Olsthoorn, Alisha V.

2012-01-01

During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, host gene expression is severely restricted by a process of global mRNA degradation known as host shutoff, which rededicates translational machinery to the expression of viral proteins. A subset of host mRNAs is spared from shutoff, and a number of these contain cis-acting AU-rich elements (AREs) in their 3′ untranslated regions. AREs are found in labile mRNAs encoding cytokines, growth factors, and proto-oncogenes. Activation of the p38/MK2 signal transduction pathway reverses constitutive decay of ARE-mRNAs, resulting in increased protein production. The viral G-protein-coupled receptor (vGPCR) is thought to play an important role in promoting the secretion of angiogenic molecules from KSHV-infected cells during lytic replication, but to date it has not been clear how vGPCR circumvents host shutoff. Here, we demonstrate that vGPCR activates the p38/MK2 pathway and stabilizes ARE-mRNAs, augmenting the levels of their protein products. Using MK2-deficient cells, we demonstrate that MK2 is essential for maximal vGPCR-mediated ARE-mRNA stabilization. ARE-mRNAs are normally delivered to cytoplasmic ribonucleoprotein granules known as processing bodies (PBs) for translational silencing and decay. We demonstrate that PB formation is prevented during KSHV lytic replication or in response to vGPCR-mediated activation of RhoA subfamily GTPases. Together, these data show for the first time that vGPCR impacts gene expression at the posttranscriptional level, coordinating an attack on the host mRNA degradation machinery. By suppressing ARE-mRNA turnover, vGPCR may facilitate escape of certain target mRNAs from host shutoff and allow secretion of angiogenic factors from lytically infected cells. PMID:22696654

Host species shapes the co-occurrence patterns rather than diversity of stomach bacterial communities in pikas.

PubMed

Li, Huan; Li, Tongtong; Tu, Bo; Kou, Yongping; Li, Xiangzhen

2017-07-01

The mammalian stomach acts as an important barrier against ingested pathogens into the entire gastrointestinal tract, thereby playing a key role in host health. However, little is known regarding to the stomach microbial compositions in wild mammals and the factors that may influence the community compositions. Using high-throughput sequencing of the 16S rRNA gene, we characterized the stomach bacterial community compositions, diversity, and interactions in two common pika (Ochotona sp.) species in China, including Plateau pikas (Ochotona curzoniae) and Daurian pikas (Ochotona daurica) living in the Qinghai-Tibet Plateau and the Inner Mongolia Grassland, respectively. The bacterial communities can be divided into two distinct phylogenetic clusters. The most dominant bacteria in cluster I were unclassified bacteria. Cluster II was more diverse, predominantly consisting of Bacteroidetes, followed by unclassified bacteria, Firmicutes and Proteobacteria. Three dominant genera (Prevotella, Oscillospira, and Ruminococcus) in pika stomachs were significantly enriched in cluster II. In addition, seasons, host species, and sampling sites as well as body weight and sex had no significant impacts on the composition and diversity of pika stomach communities. Interestingly, Plateau pikas harbored a more complex bacterial network than Daurian pikas, and these two pika species showed different co-occurrence patterns. These results suggested that the pika stomach harbors a diverse but relatively stable and unique bacterial community, which is independent on host (host species, body weight, and sex) and measured environmental factors (sampling sites and seasons). Interestingly, host species shapes the microbial interactions rather than diversity of stomach bacterial communities in pikas, reflecting specific niche adaptation of stomach bacterial communities through species interactions.

In four shallow and mesophotic tropical reef sponges from Guam the microbial community largely depends on host identity

PubMed Central

Steinert, Georg; Taylor, Michael W.; Deines, Peter; Simister, Rachel L.; de Voogd, Nicole J.; Hoggard, Michael

2016-01-01

Sponges (phylum Porifera) are important members of almost all aquatic ecosystems, and are renowned for hosting often dense and diverse microbial communities. While the specificity of the sponge microbiota seems to be closely related to host phylogeny, the environmental factors that could shape differences within local sponge-specific communities remain less understood. On tropical coral reefs, sponge habitats can span from shallow areas to deeper, mesophotic sites. These habitats differ in terms of environmental factors such as light, temperature, and food availability, as well as anthropogenic impact. In order to study the host specificity and potential influence of varying habitats on the sponge microbiota within a local area, four tropical reef sponges, Rhabdastrella globostellata, Callyspongia sp., Rhaphoxya sp., and Acanthella cavernosa, were collected from exposed shallow reef slopes and a deep reef drop-off. Based on 16S rRNA gene pyrosequencing profiles, beta diversity analyses revealed that each sponge species possessed a specific microbiota that was significantly different to those of the other species and exhibited attributes that are characteristic of high- and/or low-microbial-abundance sponges. These findings emphasize the influence of host identity on the associated microbiota. Dominant sponge- and seawater-associated bacterial phyla were Chloroflexi, Cyanobacteria, and Proteobacteria. Comparison of individual sponge taxa and seawater samples between shallow and deep reef sites revealed no significant variation in alpha diversity estimates, while differences in microbial beta diversity (variation in community composition) were significant for Callyspongia sp. sponges and seawater samples. Overall, the sponge-associated microbiota is significantly shaped by host identity across all samples, while the effect of habitat differentiation seems to be less predominant in tropical reef sponges. PMID:27114882

Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host Immune Function and Reduces Nosema ceranae Infections

PubMed Central

Li, Wenfeng; Evans, Jay D.; Huang, Qiang; Rodríguez-García, Cristina; Liu, Jie; Hamilton, Michele; Grozinger, Christina M.; Webster, Thomas C.; Su, Songkun

2016-01-01

ABSTRACT Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd), which is a negative regulator of host immune function. Our studies found that nkd mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown of nkd transcripts in Nosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host nkd gene can activate honey bee immune responses, suppress the reproduction of N. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration. IMPORTANCE Given the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors. Here, we demonstrate that knocking down the honey bee immune repressor-encoding nkd gene can suppress the reproduction of N. ceranae and improve the overall health of honey bees, which highlights the potential role of host-derived and RNAi-based therapeutics in controlling the infections in honey bees. The information obtained from this study will have positive implications for honey bee disease management practices. PMID:27613683

Workshop focuses on study of climate's effects on health

NASA Astrophysics Data System (ADS)

Diaz, Henry F.; Epstein, Paul R.; Aron, Joan L.; Confalonieri, Ulisses E. C.

Changes in temperature, precipitation, humidity, and storm patterns influence upsurges of waterborne diseases such as hepatitis, shigella dysentery, typhoid, and cholera as well as vector-borne pathogens such as malaria, dengue, yellow fever, encephalitis, schistosomiasis, plague, and hantavirus. Cycles of flooding and drought directly affect factors such as the multiplication rates of disease vectors, the biting rate of vectors, and the amount of host-vector interaction. Indirectly, climate influences parameters important to vector spread or survival such as agricultural practices, the disruption of ecosystems, or changes in social systems and practices, which in turn change the relationship between the parasite, the vector, its predators, and the host.

Perspectives of host faculty and trainees on international visiting faculty to paediatric academic departments in East Africa

PubMed Central

Russ, Christiana M; Ganapathi, Lakshmi; Marangu, Diana; Silverman, Melanie; Kija, Edward; Bakeera-Kitaka, Sabrina; Laving, Ahmed

2016-01-01

Background Investments in faculty exchanges to build physician workforce capacity are increasing. Little attention has been paid to the expectations of host institution faculty and trainees. This prospective qualitative research study explored faculty and resident perspectives about guest faculty in paediatric departments in East Africa, asking (1) What are the benefits and challenges of hosting guest faculty, (2) What factors influence the effectiveness of faculty visits and (3) How do host institutions prepare for faculty visits? Methods We recruited 36 faculty members and residents from among four paediatric departments in East Africa to participate in semistructured interviews which were audio recorded and transcribed. Data were qualitatively analysed using principles of open coding and thematic analysis. We achieved saturation of themes. Results Benefits of faculty visits varied based on the size and needs of host institutions. Emergent themes included the importance of guest faculty time commitment, and mutual preparation to ensure that visit goals and scheduling met host needs. We documented conflicts that developed around guest emotional responses and ethical approaches to clinical resource limitations, which some hosts tried to prepare for and mitigate. Imbalance in resources led to power differentials; some hosts sought partnerships to re-establish control over the process of having guests. Conclusions We identified that guest faculty can assist paediatric institutions in building capacity; however, effective visits require: (1) mutually agreed on goals with appropriate scheduling, visit length and commitment to ensure that the visits meet the host's needs, (2) careful selection and preparation of guest faculty to meet the host's goals, (3) emotional preparation by prospective guests along with host orientation to clinical work in the host's setting and (4) attention to funding sources for the visit and mitigation of resulting power differentials. PMID:28588960

Role of Helicobacter pylori in gastric cancer: Updates

PubMed Central

Khatoon, Jahanarah; Rai, Ravi Prakash; Prasad, Kashi Nath

2016-01-01

Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC. PMID:26909129

Ecology of the interaction between Ixodes loricatus (Acari: Ixodidae) and Akodon azarae (Rodentia: Criceridae).

PubMed

Colombo, Valeria C; Nava, Santiago; Antoniazzi, Leandro R; Monje, Lucas D; Racca, Andrea L; Guglielmone, Alberto A; Beldomenico, Pablo M

2015-10-01

The present study explores associations of different factors (i.e. host parameters, presence of other ectoparasites and [mainly biotic] environmental factors) with burdens of Ixodes loricatus immature stages in one of its main hosts in Argentina, the rodent Akodon azarae. For 2 years, rodents were trapped and sampled monthly at 16 points located in four different sites in the Parana River Delta region. Data were analysed with generalized linear mixed models with a negative binomial response (counts of larvae or nymphs). The independent variables assessed were (a) environmental: trapping year, presence of cattle, type of vegetation, rodent abundance; (b) host parameters: body length, sex, body condition, blood cell counts, natural antibody titers and (c) co-infestation with other ectoparasites. Two-way interaction terms deemed a priori as relevant were also included in the analysis. Most of the associations investigated were found significant, but in general, the direction and magnitude of the associations were context-dependent. An exception was the presence of cattle, which was consistently negatively associated with both larvae and nymphs independently of all other variables considered and had the strongest effect on tick burdens. Mites, fleas and Amblyomma triste were also significantly associated (mostly positively) with larval and nymph burdens, and in many cases, they influenced associations with environmental or host factors. Our findings strongly support that raising cattle may have a substantial impact on the dynamics of I. loricatus and that interactions within the ectoparasite community may be an important-but generally ignored-driver of tick dynamics.

Phylogeographical patterns among Mediterranean sepiolid squids and their Vibrio symbionts: environment drives specificity among sympatric species.

PubMed

Zamborsky, D J; Nishiguchi, M K

2011-01-01

Bobtail squid from the genera Sepiola and Rondeletiola (Cephalopoda: Sepiolidae) form mutualistic associations with luminous Gram-negative bacteria (Gammaproteobacteria: Vibrionaceae) from the genera Vibrio and Photobacterium. Symbiotic bacteria proliferate inside a bilobed light organ until they are actively expelled by the host into the surrounding environment on a diel basis. This event results in a dynamic symbiont population with the potential to establish the symbiosis with newly hatched sterile (axenic) juvenile sepiolids. In this study, we examined the genetic diversity found in populations of sympatric sepiolid squid species and their symbionts by the use of nested clade analysis with multiple gene analyses. Variation found in the distribution of different species of symbiotic bacteria suggests a strong influence of abiotic factors in the local environment, affecting bacterial distribution among sympatric populations of hosts. These abiotic factors include temperature differences incurred by a shallow thermocline, as well as a lack of strong coastal water movement accompanied by seasonal temperature changes in overlapping niches. Host populations are stable and do not appear to have a significant role in the formation of symbiont populations relative to their distribution across the Mediterranean Sea. Additionally, all squid species examined (Sepiola affinis, S. robusta, S. ligulata, S. intermedia, and Rondeletiola minor) are genetically distinct from one another regardless of location and demonstrate very little intraspecific variation within species. These findings suggest that physical boundaries and distance in relation to population size, and not host specificity, are important factors in limiting or defining gene flow within sympatric marine squids and their associated bacterial symbionts in the Mediterranean Sea.

Natural history of chronic hepatitis B virus infection from infancy to adult life - the mechanism of inflammation triggering and long-term impacts.

PubMed

Wu, Jia-Feng; Chang, Mei-Hwei

2015-10-20

Chronic hepatitis B virus (HBV) infection in endemic areas usually starts since infancy and early childhood and persists lifelong. The clinical course varies among different chronic infected subjects. Majority of chronic HBV infected children present with immune-tolerant status initially, experience the immune clearance phase with various degree of liver injury during or beyond puberty, and then enter the inactive phase after hepatitis B e antigen (HBeAg) seroconversion. Part of them may have HBV DNA titers elevation with hepatitis flare after HBeAg seroconversion, the so call HBeAg-negative hepatitis flare. Liver cirrhosis, and even hepatocellular carcinoma may develop afterward.The complex course of chronic HBV infection is associated with the age/route of viral acquisition, host factors such as immune and endocrine factors, viral factors, and host-viral interactions. The adrenarche and puberty onset modulate the start of immune clearance and the severity of liver inflammation in chronic HBV infected children. The genotype and phenotype of human cytokines, innate immunity, and human leukocyte antigens are also associated with the onset of immune clearance of HBV and severity of inflammation. Immune escape HBV mutant strains, emerged during the immune clearance phase under host immune surveillance, may cause different impacts on viral biosynthesis, host immune responses, and clinical course.Early events in childhood during chronic HBV infection may serve as important predictors for the later outcome in adulthood. Understanding the mechanisms triggering liver inflammation and their long-term impacts may enhance the development of better and earlier therapeutic strategies for patients with chronic HBV infection.

Taxonomic distinctness and richness of helminth parasite assemblages of freshwater fishes in Mexican hydrological basins.

PubMed

Quiroz-Martínez, Benjamín; Salgado-Maldonado, Guillermo

2013-01-01

In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra--host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern--nearctic and southern--neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance--decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis.

Taxonomic Distinctness and Richness of Helminth Parasite Assemblages of Freshwater Fishes in Mexican Hydrological Basins

PubMed Central

Quiroz-Martínez, Benjamín; Salgado-Maldonado, Guillermo

2013-01-01

In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra - host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern - nearctic and southern - neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance - decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis. PMID:24086342

The bacteriome-mycobiome interaction and antifungal host defense.

PubMed

Oever, Jaap Ten; Netea, Mihai G

2014-11-01

Large communities of microorganisms, collectively termed the microbiome, inhabit our body surfaces. With the advent of next-generation sequencing, the diversity and abundance of these communities are being unravelled. Besides an imporant role in metabolic processes, the microbiome is essential for proper functioning of our immune system, including the defense against fungi. Despite the progress of the past years, studies aimed at characterizing our fungal colonizers (the mycobiome) are limited; nevertheless fungi are important players of the microbiome, either as a cofactor in disease or as potential pathogens. In this review, we describe the role of the bacterial microbiome in antifungal host defense. On the one hand, bacteria provide colonization resistance to fungi, inhibit Candida virulence by preventing yeast-hyphal transition and contribute to epithelial integrity, all factors are important for the pathogenesis of invasive fungal disease. On the other hand, several bacterial species modulate mucosal (antifungal) immune responses. Murine studies demonstrate important effects of the microbiome on the antifungal responses of T-helper 17 cells, regulatory T cells and innate lymphoid cells. Inferred from these studies, perturbation of the healthy microbiome should be avoided and microbiome manipulation and interventions based on bacteria-derived pathways involved in immunomodulation are attractive options for modulating antifungal host defense. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gut microbiome and the risk factors in central nervous system autoimmunity.

PubMed

Ochoa-Repáraz, Javier; Kasper, Lloyd H

2014-11-17

Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

A North American isolate of Fusarium graminearum: toxicity and biosynthesis of a new type A trichothecene

USDA-ARS?s Scientific Manuscript database

Fusarium graminearum is one of the economically most important plant pathogens causing diseases such as Fusarium Head Blight (FHB) of small grain cereals and ear rot of maize. The mycotoxin deoxynivalenol (DON) produced by F. graminearum is a virulence factor in wheat and probably also on other host...

Host cell interactions of outer membrane vesicle-associated virulence factors of Enterohemorrhagic Escherichia coli O157: intracellular delivery, trafficking and mechanisms of cell injury

USDA-ARS?s Scientific Manuscript database

Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, confocal laser...

Morphology, diet, and temperature dependent host-free survival of the boll weevil, Anthonomus grandis (Coleoptera: Curculionidae)

USDA-ARS?s Scientific Manuscript database

The boll weevil, Anthonomus grandis grandis Boheman, is an important pest of cotton (Gossypium spp.) in South America, Mexico, and southernmost Texas in the United States. A key factor in the persistence of the boll weevil is its ability to survive the non-cotton season. Mechanisms facilitating this...

KF-finder: identification of key factors from host-microbial networks in cervical cancer.

PubMed

Hu, Jialu; Gao, Yiqun; Zheng, Yan; Shang, Xuequn

2018-04-24

The human body is colonized by a vast number of microbes. Microbiota can benefit many normal life processes, but can also cause many diseases by interfering the regular metabolism and immune system. Recent studies have demonstrated that the microbial community is closely associated with various types of cell carcinoma. The search for key factors, which also refer to cancer causing agents, can provide an important clue in understanding the regulatory mechanism of microbiota in uterine cervix cancer. In this paper, we investigated microbiota composition and gene expression data for 58 squamous and adenosquamous cell carcinoma. A host-microbial covariance network was constructed based on the 16s rRNA and gene expression data of the samples, which consists of 259 abundant microbes and 738 differentially expressed genes (DEGs). To search for risk factors from host-microbial networks, the method of bi-partite betweenness centrality (BpBC) was used to measure the risk of a given node to a certain biological process in hosts. A web-based tool KF-finder was developed, which can efficiently query and visualize the knowledge of microbiota and differentially expressed genes (DEGs) in the network. Our results suggest that prevotellaceade, tissierellaceae and fusobacteriaceae are the most abundant microbes in cervical carcinoma, and the microbial community in cervical cancer is less diverse than that of any other boy sites in health. A set of key risk factors anaerococcus, hydrogenophilaceae, eubacterium, PSMB10, KCNIP1 and KRT13 have been identified, which are thought to be involved in the regulation of viral response, cell cycle and epithelial cell differentiation in cervical cancer. It can be concluded that permanent changes of microbiota composition could be a major force for chromosomal instability, which subsequently enables the effect of key risk factors in cancer. All our results described in this paper can be freely accessed from our website at http://www.nwpu-bioinformatics.com/KF-finder/ .

Host-choice reduces, but does not eliminate, the negative effects of a multi-species diet for an herbivorous beetle.

PubMed

Wetzel, William C; Thaler, Jennifer S

2018-02-01

A consequence of plant diversity is that it can allow or force herbivores to consume multiple plant species, which studies indicate can have major effects on herbivore fitness. An underappreciated but potentially important factor modulating the consequences of multi-species diets is the extent to which herbivores can choose their diets versus being forced to consume specific host-plant sequences. We examined how host-selection behavior alters the effects of multi-species diets using the Colorado potato beetle (Leptinotarsa decemlineata) and diets of potato plants (Solanum tuberosum), tomato plants (S. lycopersicum), or both. When we gave beetles simultaneous access to both plants, allowing them to choose their diets, their final mass was within 0.1% of the average mass across both monocultures and 43.6% lower than mass on potato, the superior host in monoculture. This result indicates these beetles do not benefit from a mixed diet, and that the presence of tomato, an inferior but suitable host, makes it difficult to use potato. In contrast, when we forced beetles to switch between host species, their final mass was 37.8% less than the average of beetles fed constant diets of either host species and within 3.5% of the mass on tomato even though they also fed on potato. This indicates preventing host-selection behavior magnified the negative effects of this multi-species diet. Our results imply that ecological contexts that constrain host-selection or force host-switches, such as communities with competition or predation, will lead plant species diversity to reduce the performance of insect herbivores.

Common themes in microbial pathogenicity revisited.

PubMed Central

Finlay, B B; Falkow, S

1997-01-01

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics. PMID:9184008

Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

PubMed Central

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas

2014-01-01

ABSTRACT The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity. PMID:24403578

Policing of gut microbiota by the adaptive immune system.

PubMed

Dollé, Laurent; Tran, Hao Q; Etienne-Mesmin, Lucie; Chassaing, Benoit

2016-02-12

The intestinal microbiota is a large and diverse microbial community that inhabits the intestine, containing about 100 trillion bacteria of 500-1000 distinct species that, collectively, provide benefits to the host. The human gut microbiota composition is determined by a myriad of factors, among them genetic and environmental, including diet and medication. The microbiota contributes to nutrient absorption and maturation of the immune system. As reciprocity, the host immune system plays a central role in shaping the composition and localization of the intestinal microbiota. Secretory immunoglobulins A (sIgAs), component of the adaptive immune system, are important player in the protection of epithelium, and are known to have an important impact on the regulation of microbiota composition. A recent study published in Immunity by Fransen and colleagues aimed to mechanistically decipher the interrelationship between sIgA and microbiota diversity/composition. This commentary will discuss these important new findings, as well as how future therapies can ultimately benefit from such discovery.

Regulation of host-pathogen interactions via the post-transcriptional Csr/Rsm system.

PubMed

Kusmierek, Maria; Dersch, Petra

2018-02-01

A successful colonization of specific hosts requires a rapid and efficient adaptation of the virulence-relevant gene expression program by bacterial pathogens. An important element in this endeavor is the Csr/Rsm system. This multi-component, post-transcriptional control system forms a central hub within complex regulatory networks and coordinately adjusts virulence properties with metabolic and physiological attributes of the pathogen. A key function is elicited by the RNA-binding protein CsrA/RsmA. CsrA/RsmA interacts with numerous target mRNAs, many of which encode crucial virulence factors, and alters their translation, stability or elongation of transcription. Recent studies highlighted that important colonization factors, toxins, and bacterial secretion systems are under CsrA/RsmA control. CsrA/RsmA deficiency impairs host colonization and attenuates virulence, making this post-transcriptional regulator a suitable drug target. The CsrA/RsmA protein can be inactivated through sequestration by non-coding RNAs, or via binding to specific highly abundant mRNAs and interacting proteins. The wide range of interaction partners and RNA targets, as well as the overarching, interlinked genetic control circuits illustrate the complexity of this regulatory system in the different pathogens. Future work addressing spatio-temporal changes of Csr/Rsm-mediated control during the course of an infection will help us to understand how bacteria reprogram their expression profile to cope with continuous changes experienced in colonized niches. Copyright © 2017 Elsevier Ltd. All rights reserved.

The immunological contribution of NF-κB within the tumor microenvironment: A potential protective role of zinc as an anti-tumor agent

PubMed Central

Bao, Bin; Thakur, Archana; Li, Yiwei; Ahmad, Aamir; Azmi, Asfar S.; Banerjee, Sanjeev; Kong, Dejuan; Ali, Shadan; Lum, Lawrence G.; Sarkar, Fazlul H.

2013-01-01

Over decades, cancer treatment has been mainly focused on targeting cancer cells and not much attention to host tumor microenvironment. Recent advances suggest that the tumor microenvironment requires in-depth investigation for understanding the interactions between tumor cell biology and immunobiology in order to optimize therapeutic approaches. Tumor microenvironment consists of cancer cells and tumor associated reactive fibroblasts, infiltrating non-cancer cells, secreted soluble factors or molecules, and non-cellular support materials. Tumor associated host immune cells such as Th1, Th2, Th17, regulatory cells, dendritic cells, macrophages, and myeloid-derived suppressor cells are major components of the tumor microenvironment. Accumulating evidence suggests that these tumor associated immune cells may play important roles in cancer development and progression. However, the exact functions of these cells in the tumor microenvironment are poorly understood. In the tumor microenvironment, NF-κB plays an important role in cancer development and progression because this is a major transcription factor which regulates immune functions within the tumor microenvironment. In this review, we will focus our discussion on the immunological contribution of NF-κB in tumor associated host immune cells within the tumor microenvironment. We will also discuss the potential protective role of zinc, a well-known immune response mediator, in the regulation of these immune cells and cancer cells in the tumor microenvironment especially because zinc could be useful for conditioning the tumor microenvironment toward innovative cancer therapy. PMID:22155217

PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features

PubMed Central

Espinosa, J. C.; Nonno, R.; Di Bari, M.; Aguilar-Calvo, P.; Pirisinu, L.; Fernández-Borges, N.; Vanni, I.; Vaccari, G.; Marín-Moreno, A.; Frassanito, P.; Lorenzo, P.; Agrimi, U.

2016-01-01

ABSTRACT Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features. IMPORTANCE The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model. PMID:27654300

Viral Interference and Persistence in Mosquito-Borne Flaviviruses.

PubMed

Salas-Benito, Juan Santiago; De Nova-Ocampo, Mónica

2015-01-01

Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

The bacterial skin microbiome in psoriatic arthritis, an unexplored link in pathogenesis: challenges and opportunities offered by recent technological advances.

PubMed

Castelino, Madhura; Eyre, Stephen; Upton, Mathew; Ho, Pauline; Barton, Anne

2014-05-01

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both the skin and gastrointestinal tract as sources of microbial triggers for PsA. In parallel with genetic studies, characterization of the host microbiota may benefit our understanding of the microbial contribution to disease pathogenesis-knowledge that may eventually inform the development of novel therapeutics.

Age-Dependent Enterocyte Invasion and Microcolony Formation by Salmonella

PubMed Central

Zhang, Kaiyi; Dupont, Aline; Torow, Natalia; Gohde, Fredrik; Leschner, Sara; Lienenklaus, Stefan; Weiss, Siegfried; Brinkmann, Melanie M.; Kühnel, Mark; Hensel, Michael; Fulde, Marcus; Hornef, Mathias W.

2014-01-01

The coordinated action of a variety of virulence factors allows Salmonella enterica to invade epithelial cells and penetrate the mucosal barrier. The influence of the age-dependent maturation of the mucosal barrier for microbial pathogenesis has not been investigated. Here, we analyzed Salmonella infection of neonate mice after oral administration. In contrast to the situation in adult animals, we observed spontaneous colonization, massive invasion of enteroabsorptive cells, intraepithelial proliferation and the formation of large intraepithelial microcolonies. Mucosal translocation was dependent on enterocyte invasion in neonates in the absence of microfold (M) cells. It further resulted in potent innate immune stimulation in the absence of pronounced neutrophil-dominated pathology. Our results identify factors of age-dependent host susceptibility and provide important insight in the early steps of Salmonella infection in vivo. We also present a new small animal model amenable to genetic manipulation of the host for the analysis of the Salmonella enterocyte interaction in vivo. PMID:25210785

Immunity in a variable world

PubMed Central

Lazzaro, Brian P.; Little, Tom J.

2008-01-01

Immune function is likely to be a critical determinant of an organism's fitness, yet most natural animal and plant populations exhibit tremendous genetic variation for immune traits. Accumulating evidence suggests that environmental heterogeneity may retard the long-term efficiency of natural selection and even maintain polymorphism, provided alternative host genotypes are favoured under different environmental conditions. ‘Environment’ in this context refers to abiotic factors such as ambient temperature or availability of nutrient resources, genetic diversity of pathogens or competing physiological demands on the host. These factors are generally controlled in laboratory experiments measuring immune performance, but variation in them is likely to be very important in the evolution of resistance to infection. Here, we review some of the literature emphasizing the complexity of natural selection on immunity. Our aim is to describe how environmental and genetic heterogeneities, often excluded from experimentation as ‘noise’, may determine the evolutionary potential of populations or the potential for interacting species to coevolve. PMID:18926975

Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility

PubMed Central

Sehgal, Anuj; Rios, Daniel

2016-01-01

Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer’s patches is essential for the efficient spread of disease to the brain. To replicate within Peyer’s patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer’s patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer’s patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases. PMID:27973593

Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility.

PubMed

Donaldson, David S; Sehgal, Anuj; Rios, Daniel; Williams, Ifor R; Mabbott, Neil A

2016-12-01

Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases.

A broad assessment of factors determining Culicoides imicola abundance: modelling the present and forecasting its future in climate change scenarios.

PubMed

Acevedo, Pelayo; Ruiz-Fons, Francisco; Estrada, Rosa; Márquez, Ana Luz; Miranda, Miguel Angel; Gortázar, Christian; Lucientes, Javier

2010-12-06

Bluetongue (BT) is still present in Europe and the introduction of new serotypes from endemic areas in the African continent is a possible threat. Culicoides imicola remains one of the most relevant BT vectors in Spain and research on the environmental determinants driving its life cycle is key to preventing and controlling BT. Our aim was to improve our understanding of the biotic and abiotic determinants of C. imicola by modelling its present abundance, studying the spatial pattern of predicted abundance in relation to BT outbreaks, and investigating how the predicted current distribution and abundance patterns might change under future (2011-2040) scenarios of climate change according to the Intergovernmental Panel on Climate Change. C. imicola abundance data from the bluetongue national surveillance programme were modelled with spatial, topoclimatic, host and soil factors. The influence of these factors was further assessed by variation partitioning procedures. The predicted abundance of C. imicola was also projected to a future period. Variation partitioning demonstrated that the pure effect of host and topoclimate factors explained a high percentage (>80%) of the variation. The pure effect of soil followed in importance in explaining the abundance of C. imicola. A close link was confirmed between C. imicola abundance and BT outbreaks. To the best of our knowledge, this study is the first to consider wild and domestic hosts in predictive modelling for an arthropod vector. The main findings regarding the near future show that there is no evidence to suggest that there will be an important increase in the distribution range of C. imicola; this contrasts with an expected increase in abundance in the areas where it is already present in mainland Spain. What may be expected regarding the future scenario for orbiviruses in mainland Spain, is that higher predicted C. imicola abundance may significantly change the rate of transmission of orbiviruses.

E1B-55K mediated regulation of RNF4 STUbL promotes HAdV gene expression.

PubMed

Müncheberg, Sarah; Hay, Ron T; Ip, Wing H; Meyer, Tina; Weiß, Christina; Brenke, Jara; Masser, Sawinee; Hadian, Kamyar; Dobner, Thomas; Schreiner, Sabrina

2018-04-25

HAdV E1B-55K is a multifunctional regulator of productive viral replication and oncogenic transformation in non-permissive mammalian cells. These functions depend on E1B-55K's posttranslational modification with the SUMO protein and its binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to form an E3 Ubiquitin ligase complex that targets antiviral host substrates for proteasomal degradation. Recently, we reported that the PML-NB-associated factor Daxx represses efficient HAdV productive infection and is proteasomally degraded via a SUMO-E1B-55K-dependent, E4orf6-independent pathway, the details of which remained to be established.RNF4, a cellular SUMO-targeted Ubiquitin ligase (STUbL), induces ubiquitinylation of specific SUMOylated proteins and plays an essential role during DNA repair. Here, we show that E1B-55K recruits RNF4 to the insoluble nuclear matrix fraction of the infected cell to support RNF4/Daxx association, promoting Daxx PTM, and thus inhibiting this antiviral factor. Removing RNF4 from infected cells using RNAi resulted in blocking the proper establishment of viral replication centers and significantly diminished viral gene expression. These results provide a model for how HAdV antagonize the antiviral host responses by exploiting the functional capacity of cellular STUbLs. Thus, RNF4 and its STUbL function represent a positive factor during lytic infection and a novel candidate for future therapeutic antiviral intervention strategies. IMPORTANCE Daxx is a PML-NB-associated transcription factor, which was recently shown to repress efficient HAdV productive infection. To counteract this antiviral measurement during infection, Daxx is degraded via a novel pathway including viral E1B-55K and host proteasomes. This virus-mediated degradation is independent of the classical HAdV E3 Ubiquitin ligase complex, which is essential during viral infection to target other host antiviral substrates. To maintain productive viral life cycle, HAdV E1B-55K early viral protein inhibits the chromatin-remodeling factor Daxx in a SUMO-dependent manner. In addition viral E1B-55K protein recruits the STUbL RNF4 and sequesters it into the insoluble fraction of the infected cell. E1B-55K promotes complex formation between RNF4 and E1B-55K targeted Daxx protein, supporting Daxx posttranslational modification prior to functional inhibition. Hence, RNF4 represents a novel host factor, which is beneficial for HAdV gene expression by supporting Daxx counteraction. In this regard, RNF4 and other STUbL proteins might represent novel targets for therapeutic intervention. Copyright © 2018 American Society for Microbiology.

Factors affecting the ecology of tick-borne encephalitis in Slovenia.

PubMed

Knap, N; Avšič-Županc, T

2015-07-01

Recognition of factors that influence the formation of tick-borne encephalitis (TBE) foci is important for assessing the risk of humans acquiring the viral infection and for establishing what can be done (within reasonable boundaries) to minimize that risk. In Slovenia, the dynamics of the TBE vector, i.e. Ixodes ricinus, was studied over a 4-year period and the prevalence of infection in ticks was established. Two groups of tick hosts were investigated: deer and small mammals. Red deer have been confirmed as having a direct influence on the incidence of TBE and rodents have been recognized as important sentinels for TBE infections, although their role in the enzootic cycle of the virus still remains to be elucidated. Last, forest and agricultural areas, which are influenced by human activity, are suitable habitats for ticks, and important for TBEV transmission and establishment. Human behaviour is also therefore an important factor and should always be considered in studies of TBE ecology.

Host-regulated Hepatitis B Virus Capsid Assembly in a Mammalian Cell-free System.

PubMed

Liu, Kuancheng; Hu, Jianming

2018-04-20

The hepatitis B virus (HBV) is an important global human pathogen and represents a major cause of hepatitis, liver cirrhosis and liver cancer. The HBV capsid is composed of multiple copies of a single viral protein, the capsid or core protein (HBc), plays multiple roles in the viral life cycle, and has emerged recently as a major target for developing antiviral therapies against HBV infection. Although several systems have been developed to study HBV capsid assembly, including heterologous overexpression systems like bacteria and insect cells, in vitro assembly using purified protein, and mammalian cell culture systems, the requirement for non-physiological concentrations of HBc and salts and the difficulty in manipulating host regulators of assembly presents major limitations for detailed studies on capsid assembly under physiologically relevant conditions. We have recently developed a mammalian cell-free system based on the rabbit reticulocyte lysate (RRL), in which HBc is expressed at physiological concentrations and assembles into capsids under near-physiological conditions. This system has already revealed HBc assembly requirements that are not anticipated based on previous assembly systems. Furthermore, capsid assembly in this system is regulated by endogenous host factors that can be readily manipulated. Here we present a detailed protocol for this cell-free capsid assembly system, including an illustration on how to manipulate host factors that regulate assembly.

Soilborne fungi have host affinity and host-specific effects on seed germination and survival in a lowland tropical forest.

PubMed

Sarmiento, Carolina; Zalamea, Paul-Camilo; Dalling, James W; Davis, Adam S; Stump, Simon M; U'Ren, Jana M; Arnold, A Elizabeth

2017-10-24

The Janzen-Connell (JC) hypothesis provides a conceptual framework for explaining the maintenance of tree diversity in tropical forests. Its central tenet-that recruits experience high mortality near conspecifics and at high densities-assumes a degree of host specialization in interactions between plants and natural enemies. Studies confirming JC effects have focused primarily on spatial distributions of seedlings and saplings, leaving major knowledge gaps regarding the fate of seeds in soil and the specificity of the soilborne fungi that are their most important antagonists. Here we use a common garden experiment in a lowland tropical forest in Panama to show that communities of seed-infecting fungi are structured predominantly by plant species, with only minor influences of factors such as local soil type, forest characteristics, or time in soil (1-12 months). Inoculation experiments confirmed that fungi affected seed viability and germination in a host-specific manner and that effects on seed viability preceded seedling emergence. Seeds are critical components of reproduction for tropical trees, and the factors influencing their persistence, survival, and germination shape the populations of seedlings and saplings on which current perspectives regarding forest dynamics are based. Together these findings bring seed dynamics to light in the context of the JC hypothesis, implicating them directly in the processes that have emerged as critical for diversity maintenance in species-rich tropical forests.

Soilborne fungi have host affinity and host-specific effects on seed germination and survival in a lowland tropical forest

PubMed Central

Dalling, James W.; Stump, Simon M.; U’Ren, Jana M.; Arnold, A. Elizabeth

2017-01-01

The Janzen–Connell (JC) hypothesis provides a conceptual framework for explaining the maintenance of tree diversity in tropical forests. Its central tenet—that recruits experience high mortality near conspecifics and at high densities—assumes a degree of host specialization in interactions between plants and natural enemies. Studies confirming JC effects have focused primarily on spatial distributions of seedlings and saplings, leaving major knowledge gaps regarding the fate of seeds in soil and the specificity of the soilborne fungi that are their most important antagonists. Here we use a common garden experiment in a lowland tropical forest in Panama to show that communities of seed-infecting fungi are structured predominantly by plant species, with only minor influences of factors such as local soil type, forest characteristics, or time in soil (1–12 months). Inoculation experiments confirmed that fungi affected seed viability and germination in a host-specific manner and that effects on seed viability preceded seedling emergence. Seeds are critical components of reproduction for tropical trees, and the factors influencing their persistence, survival, and germination shape the populations of seedlings and saplings on which current perspectives regarding forest dynamics are based. Together these findings bring seed dynamics to light in the context of the JC hypothesis, implicating them directly in the processes that have emerged as critical for diversity maintenance in species-rich tropical forests. PMID:28973927

Non-parent of Origin Expression of Numerous Effector Genes Indicates a Role of Gene Regulation in Host Adaption of the Hybrid Triticale Powdery Mildew Pathogen.

PubMed

Praz, Coraline R; Menardo, Fabrizio; Robinson, Mark D; Müller, Marion C; Wicker, Thomas; Bourras, Salim; Keller, Beat

2018-01-01

Powdery mildew is an important disease of cereals. It is caused by one species, Blumeria graminis , which is divided into formae speciales each of which is highly specialized to one host. Recently, a new form capable of growing on triticale ( B.g. triticale ) has emerged through hybridization between wheat and rye mildews ( B.g. tritici and B.g. secalis , respectively). In this work, we used RNA sequencing to study the molecular basis of host adaptation in B.g. triticale . We analyzed gene expression in three B.g. tritici isolates, two B.g. secalis isolates and two B.g. triticale isolates and identified a core set of putative effector genes that are highly expressed in all formae speciales . We also found that the genes differentially expressed between isolates of the same form as well as between different formae speciales were enriched in putative effectors. Their coding genes belong to several families including some which contain known members of mildew avirulence ( Avr ) and suppressor ( Svr ) genes. Based on these findings we propose that effectors play an important role in host adaptation that is mechanistically based on Avr-Resistance gene-Svr interactions. We also found that gene expression in the B.g. triticale hybrid is mostly conserved with the parent-of-origin, but some genes inherited from B.g. tritici showed a B.g. secalis -like expression. Finally, we identified 11 unambiguous cases of putative effector genes with hybrid-specific, non-parent of origin gene expression, and we propose that they are possible determinants of host specialization in triticale mildew. These data suggest that altered expression of multiple effector genes, in particular Avr and Svr related factors, might play a role in mildew host adaptation based on hybridization.

Exposure to the leaf litter microbiome of healthy adults protects seedlings from pathogen damage.

PubMed

Christian, Natalie; Herre, Edward Allen; Mejia, Luis C; Clay, Keith

2017-07-12

It is increasingly recognized that microbiota affect host health and physiology. However, it is unclear what factors shape microbiome community assembly in nature, and how microbiome assembly can be manipulated to improve host health. All plant leaves host foliar endophytic fungi, which make up a diverse, environmentally acquired fungal microbiota. Here, we experimentally manipulated assembly of the cacao tree ( Theobroma cacao ) fungal microbiome in nature and tested the effect of assembly outcome on host health. Using next-generation sequencing, as well as culture-based methods coupled with Sanger sequencing, we found that manipulating leaf litter exposure and location within the forest canopy significantly altered microbiome composition in cacao. Exposing cacao seedlings to leaf litter from healthy conspecific adults enriched the seedling microbiome with Colletotrichum tropicale , a fungal endophyte known to enhance pathogen resistance of cacao seedlings by upregulating host defensive pathways. As a result, seedlings exposed to healthy conspecific litter experienced reduced pathogen damage. Our results link processes that affect the assembly and composition of microbiome communities to their functional consequences for host success, and have broad implications for understanding plant-microbe interactions. Deliberate manipulation of the plant-fungal microbiome also has potentially important applications for cacao production and other agricultural systems in general. © 2017 The Author(s).

Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies.

PubMed

Al-Bader, Nadia; Sheppard, Donald C

2016-11-16

Invasive aspergillosis is a life-threatening infection caused by the opportunistic filamentous fungus Aspergillus fumigatus. Patients undergoing haematopoietic stem cell transplant (HSCT) for the treatment of hematological malignancy are at particularly high risk of developing this fatal infection. The susceptibility of HSCT patients to infection with A. fumigatus is a consequence of a complex interplay of both fungal and host factors. Here we review our understanding of the host-pathogen interactions underlying the susceptibility of the immunocompromised host to infection with A. fumigatus with a focus on the experimental validation of fungal and host factors relevant to HSCT patients. These include fungal factors such as secondary metabolites, cell wall constituents, and metabolic adaptations that facilitate immune evasion and survival within the host microenvironment, as well as the innate and adaptive immune responses involved in host defense against A. fumigatus.

Local adaptation of plant viruses: lessons from experimental evolution.

PubMed

Elena, Santiago F

2017-04-01

For multihost pathogens, adaptation to multiple hosts has important implications for both applied and basic research. At the applied level, it is one of the main factors determining the probability and severity of emerging disease outbreaks. At the basic level, it is thought to be a key mechanism for the maintenance of genetic diversity both in host and pathogen species. In recent years, a number of evolution experiments have assessed the fate of plant virus populations replicating within and adapting to one single or to multiple hosts species. A first group of these experiments tackled the existence of trade-offs in fitness and virulence for viruses evolving either within a single hosts species or alternating between two different host species. A second set of experiments explored the role of genetic variability in susceptibility and resistance to infection among individuals from the same host species in the extent of virus local adaptation and of virulence. In general, when a single host species or genotype is available, these experiments show that local adaptation takes place, often but not always associated with a fitness trade-off. However, alternating between different host species or infecting resistant host genotypes may select for generalist viruses that experience no fitness cost. Therefore, the expected cost of generalism, arising from antagonistic pleiotropy and other genetic mechanisms generating fitness trade-offs between hosts, could not be generalized and strongly depend on the characteristics of each particular pathosystem. At the genomic level, these studies show pervasive convergent molecular evolution, suggesting that the number of accessible molecular pathways leading to adaptation to novel hosts is limited. © 2016 John Wiley & Sons Ltd.

Influenza A virus-induced degradation of eukaryotic translation initiation factor 4B contributes to viral replication by suppressing IFITM3 protein expression.

PubMed

Wang, Song; Chi, Xiaojuan; Wei, Haitao; Chen, Yuhai; Chen, Zhilong; Huang, Shile; Chen, Ji-Long

2014-08-01

Although alteration in host cellular translation machinery occurs in virus-infected cells, the role of such alteration and the precise pathogenic processes are not well understood. Influenza A virus (IAV) infection shuts off host cell gene expression at transcriptional and translational levels. Here, we found that the protein level of eukaryotic translation initiation factor 4B (eIF4B), an integral component of the translation initiation apparatus, was dramatically reduced in A549 cells as well as in the lung, spleen, and thymus of mice infected with IAV. The decrease in eIF4B level was attributed to lysosomal degradation of eIF4B, which was induced by viral NS1 protein. Silencing eIF4B expression in A549 cells significantly promoted IAV replication, and conversely, overexpression of eIF4B markedly inhibited the viral replication. Importantly, we observed that eIF4B knockdown transgenic mice were more susceptible to IAV infection, exhibiting faster weight loss, shorter survival time, and more-severe organ damage. Furthermore, we demonstrated that eIF4B regulated the expression of interferon-induced transmembrane protein 3 (IFITM3), a critical protein involved in immune defense against a variety of RNA viruses, including influenza virus. Taken together, our findings reveal that eIF4B plays an important role in host defense against IAV infection at least by regulating the expression of IFITM3, which restricts viral entry and thereby blocks early stages of viral production. These data also indicate that influenza virus has evolved a strategy to overcome host innate immunity by downregulating eIF4B protein. Influenza A virus (IAV) infection stimulates the host innate immune system, in part, by inducing interferons (IFNs). Secreted IFNs activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, leading to elevated transcription of a large group of IFN-stimulated genes that have antiviral function. To circumvent the host innate immune response, influenza virus has evolved multiple strategies for suppressing the production of IFNs. Here, we show that IAV infection induces lysosomal degradation of eIF4B protein; and eIF4B inhibits IAV replication by upregulating expression of interferon-induced transmembrane protein 3 (IFITM3), a key protein that protects the host from virus infection. Our finding illustrates a critical role of eIF4B in the host innate immune response and provides novel insights into the complex mechanisms by which influenza virus interacts with its host. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The Porphyromonas gingivalis/Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer's Disease, Diabetes and Cardiovascular Diseases

PubMed Central

Carter, Chris J.; France, James; Crean, StJohn; Singhrao, Sim K.

2017-01-01

Periodontal disease is of established etiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis. Following breakdown of the host's protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer's disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. This study analyzed the relationship between the P. gingivalis/host interactome and the genes identified in genome-wide association studies (GWAS) for the aforementioned conditions using data from GWASdb (P < 1E-03) and, in some cases, from the NCBI/EBI GWAS database (P < 1E-05). Gene expression data from periodontitis or P. gingivalis microarray was compared to microarray datasets from the AD hippocampus and/or from carotid artery plaques. The results demonstrated that the host genes of the P. gingivalis interactome were significantly enriched in genes deposited in GWASdb genes related to cognitive disorders, AD and dementia, and its co-morbid conditions T2DM, obesity, and CVD. The P. gingivalis/host interactome was also enriched in GWAS genes from the more stringent NCBI-EBI database for AD, atherosclerosis and T2DM. The misregulated genes in periodontitis tissue or P. gingivalis infected macrophages also matched those in the AD hippocampus or atherosclerotic plaques. Together, these data suggest important gene/environment interactions between P. gingivalis and susceptibility genes or gene expression changes in conditions where periodontal disease is a contributory factor. PMID:29311898

The Porphyromonas gingivalis/Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer's Disease, Diabetes and Cardiovascular Diseases.

PubMed

Carter, Chris J; France, James; Crean, StJohn; Singhrao, Sim K

2017-01-01

Periodontal disease is of established etiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis . Following breakdown of the host's protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer's disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. This study analyzed the relationship between the P. gingivalis /host interactome and the genes identified in genome-wide association studies (GWAS) for the aforementioned conditions using data from GWASdb ( P < 1E-03) and, in some cases, from the NCBI/EBI GWAS database ( P < 1E-05). Gene expression data from periodontitis or P. gingivalis microarray was compared to microarray datasets from the AD hippocampus and/or from carotid artery plaques. The results demonstrated that the host genes of the P. gingivalis interactome were significantly enriched in genes deposited in GWASdb genes related to cognitive disorders, AD and dementia, and its co-morbid conditions T2DM, obesity, and CVD. The P. gingivalis /host interactome was also enriched in GWAS genes from the more stringent NCBI-EBI database for AD, atherosclerosis and T2DM. The misregulated genes in periodontitis tissue or P. gingivalis infected macrophages also matched those in the AD hippocampus or atherosclerotic plaques. Together, these data suggest important gene/environment interactions between P. gingivalis and susceptibility genes or gene expression changes in conditions where periodontal disease is a contributory factor.

OncomiR Addiction Is Generated by a miR-155 Feedback Loop in Theileria-Transformed Leukocytes

PubMed Central

Medjkane, Souhila; Perichon, Martine; Yin, Qinyan; Flemington, Erik; Weitzman, Matthew D.; Weitzman, Jonathan B.

2013-01-01

The intracellular parasite Theileria is the only eukaryote known to transform its mammalian host cells. We investigated the host mechanisms involved in parasite-induced transformation phenotypes. Tumour progression is a multistep process, yet ‘oncogene addiction’ implies that cancer cell growth and survival can be impaired by inactivating a single gene, offering a rationale for targeted molecular therapies. Furthermore, feedback loops often act as key regulatory hubs in tumorigenesis. We searched for microRNAs involved in addiction to regulatory loops in leukocytes infected with Theileria parasites. We show that Theileria transformation involves induction of the host bovine oncomiR miR-155, via the c-Jun transcription factor and AP-1 activity. We identified a novel miR-155 target, DET1, an evolutionarily-conserved factor involved in c-Jun ubiquitination. We show that miR-155 expression led to repression of DET1 protein, causing stabilization of c-Jun and driving the promoter activity of the BIC transcript containing miR-155. This positive feedback loop is critical to maintain the growth and survival of Theileria-infected leukocytes; transformation is reversed by inhibiting AP-1 activity or miR-155 expression. This is the first demonstration that Theileria parasites induce the expression of host non-coding RNAs and highlights the importance of a novel feedback loop in maintaining the proliferative phenotypes induced upon parasite infection. Hence, parasite infection drives epigenetic rewiring of the regulatory circuitry of host leukocytes, placing miR-155 at the crossroads between infection, regulatory circuits and transformation. PMID:23637592

Questions about the behaviour of bacterial pathogens in vivo.

PubMed Central

Smith, H

2000-01-01

Bacterial pathogens cause disease in man and animals. They have unique biological properties, which enable them to colonize mucous surfaces, penetrate them, grow in the environment of the host, inhibit or avoid host defences and damage the host. The bacterial products responsible for these five biological requirements are the determinants of pathogenicity (virulence determinants). Current knowledge comes from studies in vitro, but now interest is increasing in how bacteria behave and produce virulence determinants within the infected host. There are three aspects to elucidate: bacterial activities, the host factors that affect them and the metabolic interactions between the two. The first is relatively easy to accomplish and, recently, new methods for doing this have been devised. The second is not easy because of the complexity of the environment in vivo and its ever-changing face. Nevertheless, some information can be gained from the literature and by new methodology. The third aspect is very difficult to study effectively unless some events in vivo can be simulated in vitro. The objectives of the Discussion Meeting were to describe the new methods and to show how they, and conventional studies, are revealing the activities of bacterial pathogens in vivo. This paper sets the scene by raising some questions and suggesting, with examples, how they might be answered. Bacterial growth in vivo is the primary requirement for pathogenicity. Without growth, determinants of the other four requirements are not formed. Results from the new methods are underlining this point. The important questions are as follows. What is the pattern of a developing infection and the growth rates and population sizes of the bacteria at different stages? What nutrients are present in vivo and how do they change as infection progresses and relate to growth rates and population sizes? How are these nutrients metabolized and by what bacterial mechanisms? Which bacterial processes handle nutrient deficiencies and antagonistic conditions that may arise? Conventional and new methods can answer the first question and part of the second; examples are described. The difficulties of trying to answer the last two are discussed. Turning to production in vivo of determinants of mucosal colonization, penetration, interference with host defence and damage to the host, here are the crucial questions. Are putative determinants, which have been recognized by studies in vitro, produced in vivo and are they relevant to virulence? Can hitherto unknown virulence determinants be recognized by examining bacteria grown in vivo? Does the complement of virulence determinants change as infection proceeds? Are regulatory processes recognized in vitro, such as ToxR/ToxS, PhoP/PhoQ, quorum sensing and type III secretion, operative in vivo? What environmental factors affect virulence determinant production in vivo and by what metabolic processes? Examples indicate that the answers to the first four questions are 'yes' in most but not all cases. Attempts to answer the last, and most difficult, question are also described. Finally, sialylation of the lipopolysaccharide of gonococci in vivo by host-derived cytidine 5'-mono-phospho-N-acetyl neuraminic acid, and the effect of host lactate are described. This investigation revealed a new bacterial component important in pathogenicity, the host factors responsible for its production and the metabolism involved. PMID:10874729

Habitat and Host Indicate Lineage Identity in Colletotrichum gloeosporioides s.l. from Wild and Agricultural Landscapes in North America

PubMed Central

Doyle, Vinson P.; Oudemans, Peter V.; Rehner, Stephen A.; Litt, Amy

2013-01-01

Understanding the factors that drive the evolution of pathogenic fungi is central to revealing the mechanisms of virulence and host preference, as well as developing effective disease control measures. Prerequisite to these pursuits is the accurate delimitation of species boundaries. Colletotrichum gloeosporioides s.l. is a species complex of plant pathogens and endophytic fungi for which reliable species recognition has only recently become possible through a multi-locus phylogenetic approach. By adopting an intensive regional sampling strategy encompassing multiple hosts within and beyond agricultural zones associated with cranberry (Vaccinium macrocarpon Aiton), we have integrated North America strains of Colletotrichum gloeosporioides s.l. from these habitats into a broader phylogenetic framework. We delimit species on the basis of genealogical concordance phylogenetic species recognition (GCPSR) and quantitatively assess the monophyly of delimited species at each of four nuclear loci and in the combined data set with the genealogical sorting index (gsi). Our analysis resolved two principal lineages within the species complex. Strains isolated from cranberry and sympatric host plants are distributed across both of these lineages and belong to seven distinct species or terminal clades. Strains isolated from V. macrocarpon in commercial cranberry beds belong to four species, three of which are described here as new. Another species, C. rhexiae Ellis & Everh., is epitypified. Intensive regional sampling has revealed a combination of factors, including the host species from which a strain has been isolated, the host organ of origin, and the habitat of the host species, as useful indicators of species identity in the sampled regions. We have identified three broadly distributed temperate species, C. fructivorum, C. rhexiae, and C. nupharicola, that could be useful for understanding the microevolutionary forces that may lead to species divergence in this important complex of endophytes and plant pathogens. PMID:23671594

Phylogenetic and geographic patterns of bartonella host shifts among bat species

PubMed Central

McKee, Clifton D.; Hayman, David T. S.; Kosoy, Michael Y.; Webb, Colleen T.

2016-01-01

The influence of factors contributing to parasite diversity in individual hosts and communities are increasingly studied, but there has been less focus on the dominant processes leading to parasite diversification. Using bartonella infections in bats as a model system, we explored the influence of three processes that can contribute to bartonella diversification and lineage formation: (1) spatial correlation in the invasion and transmission of bartonella among bats (phylogeography); (2) divergent adaptation of bartonellae to bat hosts and arthropod vectors; and (3) evolutionary codivergence between bats and bartonellae. Using a combination of global fit techniques and ancestral state reconstruction, we found that codivergence appears to be the dominant process leading to diversification of bartonella in bats, with lineages of bartonellae corresponding to separate bat suborders, superfamilies, and families. Furthermore, we estimated the rates at which bartonellae shift bat hosts across taxonomic scales (suborders, superfamilies, and families) and found that transition rates decrease with increasing taxonomic distance, providing support for a mechanism that can contribute to the observed evolutionary congruence between bats and their associated bartonellae. While bartonella diversification is associated with host sympatry, the influence of this factor is minor compared to the influence of codivergence and there is a clear indication that some bartonella lineages span multiple regions, particularly between Africa and Southeast Asia. Divergent adaptation of bartonellae to bat hosts and arthropod vectors is apparent and can dilute the overall pattern of codivergence, however its importance in the formation of Bartonella lineages in bats is small relative to codivergence. We argue that exploring all three of these processes yields a more complete understanding of bat-bartonella relationships and the evolution of the genus Bartonella, generally. Application of these methods to other infectious bacteria and viruses could uncover common processes that lead to parasite diversification and the formation of host-parasite relationships. PMID:27473781

Variability in the intensity of nematode larvae from gastrointestinal tissues of a natural herbivore.

PubMed

van Kuren, Andrew T; Boag, Brian; Hruban, Emilie; Cattadori, Isabella M

2013-04-01

The migration of infective nematode larvae into the tissues of their hosts has been proposed as a mechanism of reducing larval mortality and increase parasite lifetime reproductive success. Given that individual hosts differ in the level of exposure, strength of immune response and physiological conditions we may expect the number of larvae in tissue to vary both between and within hosts. We used 2 gastrointestinal nematode species common in the European rabbit (Oryctolagus cuniculus) and examined how the number of larvae in the tissue changed with the immune response, parasite intensity-dependent constraints in the lumen and seasonal weather factors, in rabbits of different age, sex and breeding status. For both nematode species, larvae from the gastrointestinal tissue exhibited strong seasonal and host age-related patterns with fewer larvae recovered in summer compared to winter and more in adults than in juveniles. The number of larvae of the 2 nematodes was positively associated with intensity of parasite infection in the lumen and antibody responses while it was negatively related with air temperature and rainfall. Host sex, reproductive status and co-infection with the second parasite species contributed to increase variability between hosts. We concluded that heterogeneities in host conditions are a significant cause of variability of larval abundance in the gastrointestinal tissues. These findings can have important consequences for the dynamics of nematode infections and how parasite's life-history strategies adjust to host changes.

Differential Recognition and Hydrolysis of Host Carbohydrate Antigens by Streptococcus pneumoniae Family 98 Glycoside Hydrolases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, M.; Whitworth, G; El Warry, N

2009-01-01

The presence of a fucose utilization operon in the Streptococcus pneumoniae genome and its established importance in virulence indicates a reliance of this bacterium on the harvesting of host fucose-containing glycans. The identities of these glycans, however, and how they are harvested is presently unknown. The biochemical and high resolution x-ray crystallographic analysis of two family 98 glycoside hydrolases (GH98s) from distinctive forms of the fucose utilization operon that originate from different S. pneumoniae strains reveal that one enzyme, the predominant type among pneumococcal isolates, has a unique endo-{beta}-galactosidase activity on the LewisY antigen. Altered active site topography in themore » other species of GH98 enzyme tune its endo-{beta}-galactosidase activity to the blood group A and B antigens. Despite their different specificities, these enzymes, and by extension all family 98 glycoside hydrolases, use an inverting catalytic mechanism. Many bacterial and viral pathogens exploit host carbohydrate antigens for adherence as a precursor to colonization or infection. However, this is the first evidence of bacterial endoglycosidase enzymes that are known to play a role in virulence and are specific for distinct host carbohydrate antigens. The strain-specific distribution of two distinct types of GH98 enzymes further suggests that S. pneumoniae strains may specialize to exploit host-specific antigens that vary from host to host, a factor that may feature in whether a strain is capable of colonizing a host or establishing an invasive infection.« less

Disease induction by human microbial pathogens in plant-model systems: potential, problems and prospects.

PubMed

van Baarlen, Peter; van Belkum, Alex; Thomma, Bart P H J

2007-02-01

Relatively simple eukaryotic model organisms such as the genetic model weed plant Arabidopsis thaliana possess an innate immune system that shares important similarities with its mammalian counterpart. In fact, some human pathogens infect Arabidopsis and cause overt disease with human symptomology. In such cases, decisive elements of the plant's immune system are likely to be targeted by the same microbial factors that are necessary for causing disease in humans. These similarities can be exploited to identify elementary microbial pathogenicity factors and their corresponding targets in a green host. This circumvents important cost aspects that often frustrate studies in humans or animal models and, in addition, results in facile ethical clearance.

The potential management of oral candidiasis using anti-biofilm therapies.

PubMed

Chanda, Warren; Joseph, Thomson P; Wang, Wendong; Padhiar, Arshad A; Zhong, Mintao

2017-09-01

Candida albicans is a minor component of the oral microbiota and an opportunistic pathogen that takes advantage of the immunocompromised host and causes oral mucositis and oral candidiasis. This organism is able to undergo phenotypic modification from a yeast to hyphae growth phase, one of the key arsenals for immune cell evasion, tissue invasion and biofilm formation. The latter property coupled with overgrowth and immune compromising factors such as HIV/AIDS, cancer treatments, organ transplantation, diabetes, corticosteroid use, dentures, and broad-spectrum antibiotic use have modified the fungus from a normal component of the microflora to a foe of an oral cavity and resulting in reduced sensitivity towards commonly utilised antifungal agents. Hence, the need for alternative therapy to curb this plight is of importance. Making use of biomolecules produced by Streptococcus mutans, application of lactoferrin which is a nonspecific host defense factor found in saliva with metal chelating and broader antimicrobial properties, use of probiotics which have the capacity to boost the host immunity through eliciting Immunoglobulin A synthesis, and perturbing the pathogen's environment via competition of space and food, and application of photodynamic therapy can help to manage the burden of oral candidiasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methanogen Diversity in Indigenous and Introduced Ruminant Species on the Tibetan Plateau

PubMed Central

Huang, Xiao Dan; Martinez-Fernandez, Gonzalo; Padmanabha, Jagadish; Long, Ruijun; Denman, Stuart E.; McSweeney, Christopher S.

2016-01-01

Host factors are regarded as important in shaping the archaeal community in the rumen but few controlled studies have been performed to demonstrate this across host species under the same environmental conditions. A study was designed to investigate the structure of the methanogen community in the rumen of two indigenous (yak and Tibetan sheep) and two introduced domestic ruminant (cattle and crossbred sheep) species raised and fed under similar conditions on the high altitude Tibetan Plateau. The methylotrophic Methanomassiliicoccaceae was the predominant archaeal group in all animals even though Methanobrevibacter are usually present in greater abundance in ruminants globally. Furthermore, within the Methanomassiliicoccaceae family members from Mmc. group 10 and Mmc. group 4 were dominant in Tibetan Plateau ruminants compared to Mmc. group 12 found to be highest in other ruminants studied. Small ruminants presented the highest number of sequences that belonged to Methanomassiliicoccaceae compared to the larger ruminants. Although the methanogen community structure was different among the ruminant species, there were striking similarities between the animals in this environment. This indicates that factors such as the extreme environmental conditions and diet on the Tibetan Plateau might have a greater impact on rumen methanogen community compared to host differences. PMID:27274707

Effect of metallic silver nanoparticles on the alignment and relaxation behaviour of liquid crystalline material in smectic C* phase

NASA Astrophysics Data System (ADS)

Vimal, Tripti; Kumar Gupta, Swadesh; Katiyar, Rohit; Srivastava, Atul; Czerwinski, Michal; Krup, Katarzyna; Kumar, Sandeep; Manohar, Rajiv

2017-09-01

The influence of silver nanoparticles dispersed in a Ferroelectric Liquid Crystal (FLC) on the properties of the resultant composite system has been investigated by thermal, electro-optical, and dielectric methods. We show that the concentration of thiol capped silver nanoparticles is a critical factor in governing the alignment of nanoparticles (NPs) in the host FLC. The orientation of NPs in composite samples affects the ordering of the LC (Liquid Crystal) phase and consequently changes the various phase transition temperatures of the host LC. Formation of self-assembled 2D (two dimensional) arrays of nanoparticles is observed for high concentration of dopant in the LC, oriented perpendicular to the direction of rubbing. We propose that the molecular interaction between the thiol capped NPs and LC molecules is the key factor behind such an arrangement of NPs. Orientation of NPs has affected the relaxation behaviour and various other material parameters, significantly. A noteworthy change in DC conductivity articulates our proposed idea of the formation of 2D array of NPs perpendicular to the direction of rubbing. This comprehensive study endorses the importance of dopant concentration in modifying the properties of the host LC material.

An investigation of virulence factors of Legionella pneumophila environmental isolates.

PubMed

Arslan-Aydoğdu, Elif Özlem; Kimiran, Ayten

Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Mycorrhizal fungal growth responds to soil characteristics, but not host plant identity, during a primary lacustrine dune succession.

PubMed

Sikes, Benjamin A; Maherali, Hafiz; Klironomos, John N

2014-04-01

Soil factors and host plant identity can both affect the growth and functioning of mycorrhizal fungi. Both components change during primary succession, but it is unknown if their relative importance to mycorrhizas also changes. This research tested how soil type and host plant differences among primary successional stages determine the growth and plant effects of arbuscular mycorrhizal (AM) fungal communities. Mycorrhizal fungal community, plant identity, and soil conditions were manipulated among three stages of a lacustrine sand dune successional series in a fully factorial greenhouse experiment. Late succession AM fungi produced more arbuscules and soil hyphae when grown in late succession soils, although the community was from the same narrow phylogenetic group as those in intermediate succession. AM fungal growth did not differ between host species, and plant growth was similarly unaffected by different AM fungal communities. These results indicate that though ecological filtering and/or adaptation of AM fungi occurs during this primary dune succession, it more strongly reflects matching between fungi and soils, rather than interactions between fungi and host plants. Thus, AM fungal performance during this succession may not depend directly on the sequence of plant community succession.

Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent Protein Kinase PKR

PubMed Central

Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V.; Lokugamage, Nandadeva; Head, Jennifer A.; Ikegami, Tetsuro

2012-01-01

Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. PMID:23063407

Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR.

PubMed

Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Lokugamage, Nandadeva; Head, Jennifer A; Ikegami, Tetsuro

2013-01-20

Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

Systematic CpT (ApG) Depletion and CpG Excess Are Unique Genomic Signatures of Large DNA Viruses Infecting Invertebrates

PubMed Central

Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

2014-01-01

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

Trees wanted--dead or alive! Host selection and population dynamics in tree-killing bark beetles.

PubMed

Kausrud, Kyrre L; Grégoire, Jean-Claude; Skarpaas, Olav; Erbilgin, Nadir; Gilbert, Marius; Økland, Bjørn; Stenseth, Nils Chr

2011-01-01

Bark beetles (Coleoptera: Curculionidae, Scolytinae) feed and breed in dead or severely weakened host trees. When their population densities are high, some species aggregate on healthy host trees so that their defences may be exhausted and the inner bark successfully colonized, killing the tree in the process. Here we investigate under what conditions participating with unrelated conspecifics in risky mass attacks on living trees is an adaptive strategy, and what this can tell us about bark beetle outbreak dynamics. We find that the outcome of individual host selection may deviate from the ideal free distribution in a way that facilitates the emergence of tree-killing (aggressive) behavior, and that any heritability on traits governing aggressiveness seems likely to exist in a state of flux or cycles consistent with variability observed in natural populations. This may have implications for how economically and ecologically important species respond to environmental changes in climate and landscape (forest) structure. The population dynamics emerging from individual behavior are complex, capable of switching between "endemic" and "epidemic" regimes spontaneously or following changes in host availability or resistance. Model predictions are compared to empirical observations, and we identify some factors determining the occurrence and self-limitation of epidemics.

Helminth community structure of Tropidurus torquatus (Squamata: Tropiduridae) in a rocky outcrop area of Minas Gerais state, southeastern Brazil.

PubMed

Pereira, Felipe B; Sousa, Bernadete M; Lima, Sueli de Souza

2012-02-01

The helminth community of Tropidurus torquatus (Squamata: Tropiduridae) from a rocky outcrop area located in the state of Minas Gerais, southeastern Brazil, was studied. Ninety-two of the 110 individuals examined (83.6%) harbored helminths. Five species were found, including 3 nematodes ( Physaloptera lutzi , Parapharyngodon bainae , and Oswaldofilaria chabaudi ), 1 unidentified cestode species, and 1 acanthocephalan cystacanth also not identified. Only the nematode species had sufficient data to perform ecological analysis, with P. lutzi exhibiting the highest prevalence (67.3%). Prevalence between male and female hosts differed only for Oswaldofilaria chabaudi , with males exhibiting the highest values. The intensities of infection by P. lutzi and O. chabaudi were different among male and female hosts, with males also exhibiting the highest values. The host body size was positively related to intensity of infection for all nematode species. Local seasonality had some influence on the helminth community structure. Host diet, sexual dimorphism, and behavior (territorialism, forage strategy) represented important factors for the structure of this parasite community. In general, the helminth community was species poor, depauperate, and non-interactive, representing a typical structure observed in lizard hosts.

Critical elements in sediment-hosted deposits (clastic-dominated Zn-Pb-Ag, Mississippi Valley-type Zn-Pb, sedimentary rock-hosted Stratiform Cu, and carbonate-hosted Polymetallic Deposits): A review: Chapter 12

USGS Publications Warehouse

Marsh, Erin; Hitzman, Murray W.; Leach, David L.

2016-01-01

Some sediment-hosted base metal deposits, specifically the clastic-dominated (CD) Zn-Pb deposits, carbonate-hosted Mississippi Valley-type (MVT) deposits, sedimentary-rock hosted stratiform copper deposits, and carbonate-hosted polymetallic (“Kipushi type”) deposits, are or have been important sources of critical elements including Co, Ga, Ge, and Re. The generally poor data concerning trace element concentrations in these types of sediment-hosted ores suggest that there may be economically important concentrations of critical elements yet to be recognized.

Features of Brazilian spotted fever in two different endemic areas in Brazil.

PubMed

Angerami, Rodrigo N; Câmara, Milena; Pacola, Márcia R; Rezende, Regina C M; Duarte, Raquel M R; Nascimento, Elvira M M; Colombo, Silvia; Santos, Fabiana C P; Leite, Ruth M; Katz, Gizelda; Silva, Luiz J

2012-12-01

Brazilian spotted fever (BSF) caused by Rickettsia rickettsii is the most important rickettsiosis and the only reportable tick-borne disease in Brazil. In Brazil, the hard tick Amblyomma cajennense is the most important BSF vector; however, in São Paulo State, A. aureolatum was also recognized as a vector species in remaining Atlantic forest areas near the metropolitan area of São Paulo city. We analyzed clinical and epidemiological features of BSF cases from two distinct areas where A. cajennense (Area 1) and A. aureolatum (Area 2) are the incriminated vectors. The clinical features demonstrate the same severity pattern of BSF in both endemic areas. Differences in seasonality, patient characteristics (median age and gender), and epidemiological risk factors (animals host contact and vegetation characteristics) were observed and possibly could be attributed to the characteristics of each vector and their typical biological cycle (hosts and environment). Copyright © 2012 Elsevier GmbH. All rights reserved.

Linking dietary patterns with gut microbial composition and function

PubMed Central

Sheflin, Amy M.; Carbonero, Franck; Weir, Tiffany L.

2017-01-01

ABSTRACT Emerging insights have implicated the gut microbiota as an important factor in the maintenance of human health. Although nutrition research has focused on how direct interactions between dietary components and host systems influence human health, it is becoming increasingly important to consider nutrient effects on the gut microbiome for a more complete picture. Understanding nutrient-host-microbiome interactions promises to reveal novel mechanisms of disease etiology and progression, offers new disease prevention strategies and therapeutic possibilities, and may mandate alternative criteria to evaluate the safety of food ingredients. Here we review the current literature on diet effects on the microbiome and the generation of microbial metabolites of dietary constituents that may influence human health. We conclude with a discussion of the relevance of these studies to nutrition and public health and summarize further research needs required to realize the potential of exploiting diet-microbiota interactions for improved health. PMID:27960648

Viral Evasion and Manipulation of Host RNA Quality Control Pathways

PubMed Central

2016-01-01

Viruses have evolved diverse strategies to maximize the functional and coding capacities of their genetic material. Individual viral RNAs are often used as substrates for both replication and translation and can contain multiple, sometimes overlapping open reading frames. Further, viral RNAs engage in a wide variety of interactions with both host and viral proteins to modify the activities of important cellular factors and direct their own trafficking, packaging, localization, stability, and translation. However, adaptations increasing the information density of small viral genomes can have unintended consequences. In particular, viral RNAs have developed features that mark them as potential targets of host RNA quality control pathways. This minireview focuses on ways in which viral RNAs run afoul of the cellular mRNA quality control and decay machinery, as well as on strategies developed by viruses to circumvent or exploit cellular mRNA surveillance. PMID:27226372

Viral Evasion and Manipulation of Host RNA Quality Control Pathways.

PubMed

Hogg, J Robert

2016-08-15

Viruses have evolved diverse strategies to maximize the functional and coding capacities of their genetic material. Individual viral RNAs are often used as substrates for both replication and translation and can contain multiple, sometimes overlapping open reading frames. Further, viral RNAs engage in a wide variety of interactions with both host and viral proteins to modify the activities of important cellular factors and direct their own trafficking, packaging, localization, stability, and translation. However, adaptations increasing the information density of small viral genomes can have unintended consequences. In particular, viral RNAs have developed features that mark them as potential targets of host RNA quality control pathways. This minireview focuses on ways in which viral RNAs run afoul of the cellular mRNA quality control and decay machinery, as well as on strategies developed by viruses to circumvent or exploit cellular mRNA surveillance. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Recent 5-year Findings and Technological Advances in the Proteomic Study of HIV-associated Disorders.

PubMed

Zhang, Lijun; Jia, Xiaofang; Jin, Jun-O; Lu, Hongzhou; Tan, Zhimi

2017-04-01

Human immunodeficiency virus-1 (HIV-1) mainly relies on host factors to complete its life cycle. Hence, it is very important to identify HIV-regulated host proteins. Proteomics is an excellent technique for this purpose because of its high throughput and sensitivity. In this review, we summarized current technological advances in proteomics, including general isobaric tags for relative and absolute quantitation (iTRAQ) and stable isotope labeling by amino acids in cell culture (SILAC), as well as subcellular proteomics and investigation of posttranslational modifications. Furthermore, we reviewed the applications of proteomics in the discovery of HIV-related diseases and HIV infection mechanisms. Proteins identified by proteomic studies might offer new avenues for the diagnosis and treatment of HIV infection and the related diseases. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores.

PubMed

Sanders, Jon G; Beichman, Annabel C; Roman, Joe; Scott, Jarrod J; Emerson, David; McCarthy, James J; Girguis, Peter R

2015-09-22

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

PubMed Central

Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; Scott, Jarrod J.; Emerson, David; McCarthy, James J.; Girguis, Peter R.

2015-01-01

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut. PMID:26393325

Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV, MERS-CoV, and beyond.

PubMed

Lu, Guangwen; Wang, Qihui; Gao, George F

2015-08-01

Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that crossed the species barriers to infect humans. The mechanism of viral interspecies transmission is an important scientific question to be addressed. These coronaviruses contain a surface-located spike (S) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. In addition, the S protein needs to be cleaved by host proteases before executing fusion, making these proteases a second determinant of coronavirus interspecies infection. Here, we summarize the progress made in the past decade in understanding the cross-species transmission of SARS-CoV and MERS-CoV by focusing on the features of the S protein, its receptor-binding characteristics, and the cleavage process involved in priming. Copyright © 2015 Elsevier Ltd. All rights reserved.

Environmental variability and the transmission of haemorrhagic fever with renal syndrome in Changsha, People's Republic of China.

PubMed

Xiao, H; Gao, L D; Li, X J; Lin, X L; Dai, X Y; Zhu, P J; Chen, B Y; Zhang, X X; Zhao, J; Tian, H Y

2013-09-01

The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and environmental variables. The epidemiology of the disease was studied over a 6-year period in Changsha. Variables relating to climate, environment, rodent host distribution and disease occurrence were collected monthly and analysed using a time-series adjusted Poisson regression model. It was found that the density of the rodent host and multivariate El Niño Southern Oscillation index had the greatest effect on the transmission of HFRS with lags of 2–6 months. However, a number of climatic and environmental factors played important roles in affecting the density and transmission potential of the rodent host population. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

Vitamin D/VDR, probiotics, and gastrointestinal diseases

PubMed Central

Shang, Mei; Sun, Jun

2016-01-01

Vitamin D is an important factor in regulating inflammation, immune responses, and carcinoma inhibition via action of its receptor, vitamin D receptor (VDR). Recent studies have demonstrated the role of vitamin D/VDR in regulating host-bacterial interactions. Probiotics are beneficial bacteria with the power of supporting or favoring life on the host. In the current review, we will discuss the recent progress on the roles of vitamin D/VDR in gut microbiome and inflammation. We will summarize evidence of probiotics in modulating vitamin D/VDR and balancing gut microbiota in health and gastrointestinal diseases. Moreover, we will review the clinical application of probiotics in prevention and therapy of IBD or colon cancer. Despite of the gains, there remain several barriers to advocate broad use of probiotics in clinical therapy. We will also discuss the limits and future direction in scientific understanding of probiotics, vitamin D/VDR, and host responses. PMID:27915988

Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis.

PubMed

Marvig, Rasmus Lykke; Sommer, Lea Mette; Molin, Søren; Johansen, Helle Krogh

2015-01-01

Little is known about how within-host evolution compares between genotypically different strains of the same pathogenic species. We sequenced the whole genomes of 474 longitudinally collected clinical isolates of Pseudomonas aeruginosa sampled from 34 children and young individuals with cystic fibrosis. Our analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes. This list of genes suggests a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors. Furthermore, we find an ordered succession of mutations in key regulatory networks. Accordingly, mutations in downstream transcriptional regulators were contingent upon mutations in upstream regulators, suggesting that remodeling of regulatory networks might be important in adaptation. The characterization of genes involved in host adaptation may help in predicting bacterial evolution in patients with cystic fibrosis and in the design of future intervention strategies.

Pathogenetic aspects of uncomplicated urinary tract infection: recent advances.

PubMed

Fünfstück, R; Smith, J W; Tschäpe, H; Stein, G

1997-01-01

Urinary tract infections mostly are caused by Enterobacteriaceae; E. coli dominating in 80-90% for uncomplicated diseases. Microorganisms possessing the ability to colonize the uroepithelium (fimbriae/pili) and to cytotoxically damage cells and tissue (hemolysin) may initiate acute infection. Properties such as serum resistance, iron sequesteration, hydroxamate production and the presence of K-antigen are found in strains which persist in the host without initiating clinical symptoms. The ability of bacteria to adhere to cells of the epithelial boundary layer of the host organisms is of initial importance in the origin and progress of an infection. A variety of specific factors, e.g. glycolipids on the surface of the uroepithelium as well as cellular and humoral disorders of immunoreactions in the host determine the course of a disease. The immune response may ameliorate clinical symptoms and select urovirulent characteristics of the causative microorganism in recurrent diseases.

The Legionella pneumophila IcmS-LvgA protein complex is important for Dot/Icm-dependent intracellular growth.

PubMed

Vincent, Carr D; Vogel, Joseph P

2006-08-01

Many bacterial pathogens require a functional type IV secretion system (T4SS) for virulence. Legionella pneumophila, the causative agent of Legionnaires' disease, employs the Dot/Icm T4SS to inject a large number of protein substrates into its host, thereby altering phagosome trafficking. The L. pneumophila T4SS substrate SdeA has been shown to require the accessory factor IcmS for its export. IcmS, defined as a type IV adaptor, exists as a heterodimer with IcmW and this complex functions in a manner similar to a type III secretion chaperone. Here we report an interaction between IcmS and the previously identified virulence factor LvgA. Similar to the icmS mutant, the lvgA mutant appears to assemble a fully functional Dot/Icm complex. Both LvgA and IcmS are small, acidic proteins localized to the cytoplasm and are not exported by the Dot/Icm system, suggesting they form a novel type IV adaptor complex. Inactivation of lvgA causes a minimal defect in growth in the human monocytic cell line U937 and the environmental host Acanthamoeba castellanii. However, the lvgA mutant was severely attenuated for intracellular growth of L. pneumophila in mouse macrophages, suggesting LvgA may be a critical factor that confers host specificity.

Ultrastructure of the replication sites of positive-strand RNA viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harak, Christian; Lohmann, Volker, E-mail: volker_lohmann@med.uni-heidelberg.de

2015-05-15

Positive strand RNA viruses replicate in the cytoplasm of infected cells and induce intracellular membranous compartments harboring the sites of viral RNA synthesis. These replication factories are supposed to concentrate the components of the replicase and to shield replication intermediates from the host cell innate immune defense. Virus induced membrane alterations are often generated in coordination with host factors and can be grouped into different morphotypes. Recent advances in conventional and electron microscopy have contributed greatly to our understanding of their biogenesis, but still many questions remain how viral proteins capture membranes and subvert host factors for their need. Inmore » this review, we will discuss different representatives of positive strand RNA viruses and their ways of hijacking cellular membranes to establish replication complexes. We will further focus on host cell factors that are critically involved in formation of these membranes and how they contribute to viral replication. - Highlights: • Positive strand RNA viruses induce massive membrane alterations. • Despite the great diversity, replication complexes share many similarities. • Host factors play a pivotal role in replication complex biogenesis. • Use of the same host factors by several viruses hints to similar functions.« less

Novel collection method for volatile organic compounds (VOCs) from dogs

USDA-ARS?s Scientific Manuscript database

Host derived chemical cues are an important aspect of arthropod attraction to potential hosts. Host cues that act over longer distances include CO2, heat, and water vapor, while cues such as volatile organic compounds (VOCs) act over closer distances. Domestic dogs are important hosts for disease cy...