Staying alive: Vibrio cholerae’s cycle of environmental survival, transmission, and dissemination

PubMed Central

Jones, Christopher J.; Yildiz, Fitnat H.

2015-01-01

Infectious diseases kill nearly 9 million people annually. Bacterial pathogens are responsible for a large proportion of these diseases and the bacterial agents of pneumonia, diarrhea, and tuberculosis are leading causes of death and disability worldwide (1). Increasingly, the crucial role of non-host environments in the life cycle of bacterial pathogens is being recognized. Heightened scrutiny has been given to the biological processes impacting pathogen dissemination and survival in the natural environment, as these processes are essential for the transmission of pathogenic bacteria to new hosts. This chapter focuses on the model environmental pathogen, Vibrio cholerae, to describe recent advances in our understanding of how pathogens survive between hosts and highlight the processes necessary to support the cycle of environmental survival, transmission, and dissemination. We describe the physiological and molecular responses of V. cholerae to changing environmental conditions, focusing on its survival in aquatic reservoirs between hosts and its entry and exit from human hosts. PMID:27227302

Forest insect and fungal pathogen responses to drought [Chapter 6

Treesearch

Thomas E. Kolb; Christopher J. Fettig; Barbara J. Bentz; Jane E. Stewart; Aaron S. Weed; Jeffrey A. Hicke; Matthew P. Ayres

2016-01-01

Recent changes in precipitation patterns and in the occurrence of extreme temperature and precipitation events have been documented in many forested regions of the United States (Ryan and Vose 2012). Changes in drought intensity and frequency have the potential to alter populations and impacts of tree-damaging forest insects and pathogens (Ayers and Lombardero...

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

Omics Approaches for the Engineering of Pathogen Resistant Plants.

PubMed

Gomez-Casati, Diego F; Pagani, María A; Busi, María V; Bhadauria, Vijai

2016-01-01

The attack of different pathogens, such as bacteria, fungi and viruses has a negative impact on crop production. In counter such attacks, plants have developed different strategies involving the modification of gene expression, activation of several metabolic pathways and post-translational modification of proteins, which culminate into the accumulation of primary and secondary metabolites implicated in plant defense responses. The recent advancement in omics techniques allows the increase coverage of plants transcriptomes, proteomes and metabolomes during pathogen attack, and the modulation of the response after the infection. Omics techniques also allow us to learn more about the biological cycle of the pathogens in addition to the identification of novel virulence factors in pathogens and their host targets. Both approaches become important to decipher the mechanism underlying pathogen attacks and to develop strategies for improving disease-resistant plants. In this review, we summarize some of the contribution of genomics, transcriptomics, proteomics, metabolomics and metallomics in devising the strategies to obtain plants with increased resistance to pathogens. These approaches constitute important research tools in the development of new technologies for the protection against diseases and increase plant production.

Antagonism between salicylic and abscisic acid reflects early host-pathogen conflict and moulds plant defence responses.

PubMed

de Torres Zabala, Marta; Bennett, Mark H; Truman, William H; Grant, Murray R

2009-08-01

The importance of phytohormone balance is increasingly recognized as central to the outcome of plant-pathogen interactions. Recently it has been demonstrated that abscisic acid signalling pathways are utilized by the bacterial phytopathogen Pseudomonas syringae to promote pathogenesis. In this study, we examined the dynamics, inter-relationship and impact of three key acidic phytohormones, salicylic acid, abscisic acid and jasmonic acid, and the bacterial virulence factor, coronatine, during progression of P. syringae infection of Arabidopsis thaliana. We show that levels of SA and ABA, but not JA, appear to play important early roles in determining the outcome of the infection process. SA is required in order to mount a full innate immune responses, while bacterial effectors act rapidly to activate ABA biosynthesis. ABA suppresses inducible innate immune responses by down-regulating SA biosynthesis and SA-mediated defences. Mutant analyses indicated that endogenous ABA levels represent an important reservoir that is necessary for effector suppression of plant-inducible innate defence responses and SA synthesis prior to subsequent pathogen-induced increases in ABA. Enhanced susceptibility due to loss of SA-mediated basal resistance is epistatically dominant over acquired resistance due to ABA deficiency, although ABA also contributes to symptom development. We conclude that pathogen-modulated ABA signalling rapidly antagonizes SA-mediated defences. We predict that hormonal perturbations, either induced or as a result of environmental stress, have a marked impact on pathological outcomes, and we provide a mechanistic basis for understanding priming events in plant defence.

SIGIRR, a negative regulator of TLR/IL-1R signalling promotes Microbiota dependent resistance to colonization by enteric bacterial pathogens.

PubMed

Sham, Ho Pan; Yu, Emily Yi Shan; Gulen, Muhammet F; Bhinder, Ganive; Stahl, Martin; Chan, Justin M; Brewster, Lara; Morampudi, Vijay; Gibson, Deanna L; Hughes, Michael R; McNagny, Kelly M; Li, Xiaoxia; Vallance, Bruce A

2013-01-01

Enteric bacterial pathogens such as enterohemorrhagic E. coli (EHEC) and Salmonella Typhimurium target the intestinal epithelial cells (IEC) lining the mammalian gastrointestinal tract. Despite expressing innate Toll-like receptors (TLRs), IEC are innately hypo-responsive to most bacterial products. This is thought to prevent maladaptive inflammatory responses against commensal bacteria, but it also limits antimicrobial responses by IEC to invading bacterial pathogens, potentially increasing host susceptibility to infection. One reason for the innate hypo-responsiveness of IEC is their expression of Single Ig IL-1 Related Receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and TLR signaling. To address whether SIGIRR expression and the innate hypo-responsiveness of IEC impacts on enteric host defense, Sigirr deficient (-/-) mice were infected with the EHEC related pathogen Citrobacter rodentium. Sigirr -/- mice responded with accelerated IEC proliferation and strong pro-inflammatory and antimicrobial responses but surprisingly, Sigirr -/- mice proved dramatically more susceptible to infection than wildtype mice. Through haematopoietic transplantation studies, it was determined that SIGIRR expression by non-haematopoietic cells (putative IEC) regulated these responses. Moreover, the exaggerated responses were found to be primarily dependent on IL-1R signaling. Whilst exploring the basis for their susceptibility, Sigirr -/- mice were found to be unusually susceptible to intestinal Salmonella Typhimurium colonization, developing enterocolitis without the typical requirement for antibiotic based removal of competing commensal microbes. Strikingly, the exaggerated antimicrobial responses seen in Sigirr -/- mice were found to cause a rapid and dramatic loss of commensal microbes from the infected intestine. This depletion appears to reduce the ability of the microbiota to compete for space and nutrients (colonization resistance) with the invading pathogens, leaving the intestine highly susceptible to pathogen colonization. Thus, SIGIRR expression by IEC reflects a strategy that sacrifices maximal innate responsiveness by IEC in order to promote commensal microbe based colonization resistance against bacterial pathogens.

Eosinophils subvert host resistance to an intracellular pathogen by instigating non-protective IL-4 in CCR2-/- mice.

PubMed

Verma, A H; Bueter, C L; Rothenberg, M E; Deepe, G S

2017-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases; however, their influence on intracellular pathogens is less clear. We previously reported that CCR2 -/- mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated interleukin (IL)-4 response. We sought to identify the cellular source promulgating IL-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2 -/- animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity.

EVALUATING THE IMPACTS OF COINFECTION ON IMMUNE SYSTEM FUNCTION OF THE DEER MOUSE ( PEROMYSCUS MANICULATUS) USING SIN NOMBRE VIRUS AND BARTONELLA AS MODEL PATHOGEN SYSTEMS.

PubMed

Lehmer, Erin M; Lavengood, Kathryn; Miller, Mason; Rodgers, Jacob; Fenster, Steven D

2018-01-01

:  Simultaneous infections with multiple pathogens can alter the function of the host's immune system, often resulting in additive or synergistic morbidity. We examined how coinfection with the common pathogens Sin Nombre virus (SNV) and Bartonella sp. affected aspects of the adaptive and innate immune responses of wild deer mice ( Peromyscus maniculatus). Adaptive immunity was assessed by measuring SNV antibody production; innate immunity was determined by measuring levels of C-reactive protein (CRP) in blood and the complement activity of plasma. Coinfected mice had reduced plasma complement activity and higher levels of CRP compared to mice infected with either SNV or Bartonella. However, antibody titers of deer mice infected with SNV were more than double those of coinfected mice. Plasma complement activity and CRP levels did not differ between uninfected deer mice and those infected with only Bartonella, suggesting that comorbid SNV and Bartonella infections act synergistically, altering the innate immune response. Collectively, our results indicated that the immune response of deer mice coinfected with both SNV and Bartonella differed substantially from individuals infected with only one of these pathogens. Results of our study provided unique, albeit preliminary, insight into the impacts of coinfection on immune system function in wild animal hosts and underscore the complexity of the immune pathways that exist in coinfected hosts.

RNA-Seq analysis of resistant and susceptible sub-tropical maize lines reveals a role for kauralexins in resistance to grey leaf spot disease, caused by Cercospora zeina

USDA-ARS?s Scientific Manuscript database

Cercospora zeina is a foliar pathogen responsible for maize grey leaf spot in southern Africa that negatively impacts maize production. Plants use a variety of chemical and structural mechanisms to defend themselves against invading pathogens such as C. zeina, including the production of secondary m...

A bacterial pathogen uses dimethylsulfoniopropionate as a cue to target heat-stressed corals.

PubMed

Garren, Melissa; Son, Kwangmin; Raina, Jean-Baptiste; Rusconi, Roberto; Menolascina, Filippo; Shapiro, Orr H; Tout, Jessica; Bourne, David G; Seymour, Justin R; Stocker, Roman

2014-05-01

Diseases are an emerging threat to ocean ecosystems. Coral reefs, in particular, are experiencing a worldwide decline because of disease and bleaching, which have been exacerbated by rising seawater temperatures. Yet, the ecological mechanisms behind most coral diseases remain unidentified. Here, we demonstrate that a coral pathogen, Vibrio coralliilyticus, uses chemotaxis and chemokinesis to target the mucus of its coral host, Pocillopora damicornis. A primary driver of this response is the host metabolite dimethylsulfoniopropionate (DMSP), a key element in the global sulfur cycle and a potent foraging cue throughout the marine food web. Coral mucus is rich in DMSP, and we found that DMSP alone elicits chemotactic responses of comparable intensity to whole mucus. Furthermore, in heat-stressed coral fragments, DMSP concentrations increased fivefold and the pathogen's chemotactic response was correspondingly enhanced. Intriguingly, despite being a rich source of carbon and sulfur, DMSP is not metabolized by the pathogen, suggesting that it is used purely as an infochemical for host location. These results reveal a new role for DMSP in coral disease, demonstrate the importance of chemical signaling and swimming behavior in the recruitment of pathogens to corals and highlight the impact of increased seawater temperatures on disease pathways.

System-level impact of mitochondria on fungal virulence: to metabolism and beyond

PubMed Central

Calderone, Richard; Li, Dongmei; Traven, Ana

2015-01-01

The mitochondrion plays wide-ranging roles in eukaryotic cell physiology. In pathogenic fungi, this central metabolic organelle mediates a range of functions related to disease, from fitness of the pathogen to developmental and morphogenetic transitions to antifungal drug susceptibility. In this review, we present the latest findings in this area. We focus on likely mechanisms of mitochondrial impact on fungal virulence pathways through metabolism and stress responses, but also potentially via control over signaling pathways. We highlight fungal mitochondrial proteins that lack human homologs, and which could be inhibited as a novel approach to antifungal drug strategy. PMID:26002841

Impact of thermal stress on evolutionary trajectories of pathogen resistance in three-spined stickleback (Gasterosteus aculeatus).

PubMed

Schade, Franziska M; Shama, Lisa N S; Wegner, K Mathias

2014-07-26

Pathogens are a major regulatory force for host populations, especially under stressful conditions. Elevated temperatures may enhance the development of pathogens, increase the number of transmission stages, and can negatively influence host susceptibility depending on host thermal tolerance. As a net result, this can lead to a higher prevalence of epidemics during summer months. These conditions also apply to marine ecosystems, where possible ecological impacts and the population-specific potential for evolutionary responses to changing environments and increasing disease prevalence are, however, less known. Therefore, we investigated the influence of thermal stress on the evolutionary trajectories of disease resistance in three marine populations of three-spined sticklebacks Gasterosteus aculeatus by combining the effects of elevated temperature and infection with a bacterial strain of Vibrio sp. using a common garden experiment. We found that thermal stress had an impact on fish weight and especially on survival after infection after only short periods of thermal acclimation. Environmental stress reduced genetic differentiation (QST) between populations by releasing cryptic within-population variation. While life history traits displayed positive genetic correlations across environments with relatively weak genotype by environment interactions (GxE), environmental stress led to negative genetic correlations across environments in pathogen resistance. This reversal of genetic effects governing resistance is probably attributable to changing environment-dependent virulence mechanisms of the pathogen interacting differently with host genotypes, i.e. GPathogenxGHostxE or (GPathogenxE)x(GHostxE) interactions, rather than to pure host genetic effects, i.e. GHostxE interactions. To cope with climatic changes and the associated increase in pathogen virulence, host species require wide thermal tolerances and pathogen-resistant genotypes. The higher resistance we found for some families at elevated temperatures showed that there is evolutionary potential for resistance to Vibrio sp. in both thermal environments. The negative genetic correlation of pathogen resistance between thermal environments, on the other hand, indicates that adaptation to current conditions can be a weak predictor for performance in changing environments. The observed feedback on selective gradients exerted on life history traits may exacerbate this effect, as it can also modify the response to selection for other vital components of fitness.

Effects of oligosaccharides in a soybean meal-based diet on fermentative and immune responses in broiler chicks challenged with Eimeria acervulina

USDA-ARS?s Scientific Manuscript database

Fermentable oligosaccharides, particularly those found in soybean meal (SBM), may modulate fermentation in the ceca, thus affecting intestinal immune responses to intestinal pathogens. We hypothesized that fermentable oligosaccharides found in SBM would positively impact cecal fermentation and inte...

Eosinophils Subvert Host Resistance to an Intracellular Pathogen by Instigating Non-Protective IL-4 in CCR2−/− Mice

PubMed Central

Verma, Akash H.; Bueter, Chelsea L.; Rothenberg, Marc E.; Deepe, George S.

2016-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases, however, their influence on intracellular pathogens is less clear. We previously reported that CCR2−/− mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated IL-4 response. We sought to identify the cellular source promulgating interleukin (IL)-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2−/− animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity. PMID:27049063

Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans.

PubMed

Hoye, Bethany J; Fouchier, Ron A M; Klaassen, Marcel

2012-02-07

Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host-pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (-25.3±0.4) than their non-infected counterparts (-26.3±0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness.

Treatment of acute otitis media - challenges in the era of antibiotic resistance.

PubMed

Dagan, R

2000-12-08

The last decade is characterized by the increase in antibiotic resistance among respiratory bacterial pathogens in the presence of only modest progress in the development of new antibacterial agents to overcome this resistance. A series of recent studies show clearly that the increased resistance among the main AOM pathogens (namely Streptococcus pneumoniae and Haemophilus influenzae) is associated with a dramatic decrease in bacteriologic response to antibiotic treatment, which in turn has an impact on clinical response. Thus, the individual patient is affected by the increasing antibiotic resistance. Moreover, the society as a whole is now also affected because the carriage and spread of antibiotic resistant AOM pathogens is remarkably impacted by antibiotic treatment. New studies show the remarkable ability of antibiotics to rapidly promote nasopharyngeal carriage and spread of antibiotic-resistant AOM pathogens. In these studies, the increase in carriage of antibiotic resistant S. pneumoniae is shown already after 3-4 days from initiation of antibiotic treatment and may last for weeks to months after treatment. Children carrying antibiotic-resistant organisms transmit those organisms to their family and to their day care centers and thus a vicious cycle is created in which increased antibiotic resistance with decreased response leads to increased antibiotic use, which in turn leads to further increase in resistance. New antibiotics are not likely to improve this situation. It is clear that the challenge in the next decade is to prevent AOM rather than to treat it. Efforts to prevent AOM include improved environmental factors, immunization with bacterial and viral vaccines and some creative measures such as prevention of colonization and attachment to epithelium of AOM pathogens. Whether these efforts will prove successful or, even if successful, will only modify the clinical and bacteriologic picture presenting new challenges, only time will tell.

Cis- and trans-zeatin differentially modulate plant immunity.

PubMed

Großkinsky, Dominik K; Edelsbrunner, Kerstin; Pfeifhofer, Hartwig; van der Graaff, Eric; Roitsch, Thomas

2013-07-01

Phytohormones are essential regulators of various processes in plant growth and development. Several phytohormones are also known to regulate plant responses to environmental stress and pathogens. Only recently, cytokinins have been demonstrated to play an important role in plant immunity. Increased levels of cytokinins such as trans-zeatin, which are considered highly active, induced resistance against mainly (hemi)biotrophic pathogens in different plant species. In contrast, cis-zeatin is commonly regarded as a cytokinin exhibiting low or no activity. Here we comparatively study the impact of both zeatin isomers on the infection of Nicotiana tabacum by the (hemi)biotrophic microbial pathogen Pseudomonas syringae. We demonstrate a biological effect of cis-zeatin and a differential effect of the two zeatin isomers on symptom development, defense responses and bacterial multiplication.

Phenotypic interactions between tree hosts and invasive forest pathogens in the light of globalization and climate change

PubMed Central

2016-01-01

Invasive pathogens can cause considerable damage to forest ecosystems. Lack of coevolution is generally thought to enable invasive pathogens to bypass the defence and/or recognition systems in the host. Although mostly true, this argument fails to predict intermittent outcomes in space and time, underlining the need to include the roles of the environment and the phenotype in host–pathogen interactions when predicting disease impacts. We emphasize the need to consider host–tree imbalances from a phenotypic perspective, considering the lack of coevolutionary and evolutionary history with the pathogen and the environment, respectively. We describe how phenotypic plasticity and plastic responses to environmental shifts may become maladaptive when hosts are faced with novel pathogens. The lack of host–pathogen and environmental coevolution are aligned with two global processes currently driving forest damage: globalization and climate change, respectively. We suggest that globalization and climate change act synergistically, increasing the chances of both genotypic and phenotypic imbalances. Short moves on the same continent are more likely to be in balance than if the move is from another part of the world. We use Gremmeniella abietina outbreaks in Sweden to exemplify how host–pathogen phenotypic interactions can help to predict the impacts of specific invasive and emergent diseases. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080981

Phenotypic interactions between tree hosts and invasive forest pathogens in the light of globalization and climate change.

PubMed

Stenlid, Jan; Oliva, Jonàs

2016-12-05

Invasive pathogens can cause considerable damage to forest ecosystems. Lack of coevolution is generally thought to enable invasive pathogens to bypass the defence and/or recognition systems in the host. Although mostly true, this argument fails to predict intermittent outcomes in space and time, underlining the need to include the roles of the environment and the phenotype in host-pathogen interactions when predicting disease impacts. We emphasize the need to consider host-tree imbalances from a phenotypic perspective, considering the lack of coevolutionary and evolutionary history with the pathogen and the environment, respectively. We describe how phenotypic plasticity and plastic responses to environmental shifts may become maladaptive when hosts are faced with novel pathogens. The lack of host-pathogen and environmental coevolution are aligned with two global processes currently driving forest damage: globalization and climate change, respectively. We suggest that globalization and climate change act synergistically, increasing the chances of both genotypic and phenotypic imbalances. Short moves on the same continent are more likely to be in balance than if the move is from another part of the world. We use Gremmeniella abietina outbreaks in Sweden to exemplify how host-pathogen phenotypic interactions can help to predict the impacts of specific invasive and emergent diseases.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Author(s).

The Arabidopsis leaf transcriptome reveals distinct but also overlapping responses to colonization by phyllosphere commensals and pathogen infection with impact on plant health.

PubMed

Vogel, Christine; Bodenhausen, Natacha; Gruissem, Wilhelm; Vorholt, Julia A

2016-10-01

Plants are colonized by a variety of bacteria, most of which are not pathogenic. Currently, the plant responses to phyllosphere commensals or to pathogen infection in the presence of commensals are not well understood. Here, we examined the transcriptional response of Arabidopsis thaliana leaves to colonization by common commensal bacteria in a gnotobiotic system using RNA sequencing and conducted plant mutant assays. Arabidopsis responded differently to the model bacteria Sphingomonas melonis Fr1 (S.Fr1) and Methylobacterium extorquens PA1 (M.PA1). Whereas M.PA1 only marginally affected the expression of plant genes (< 10), S.Fr1 colonization changed the expression of almost 400 genes. For the latter, genes related to defense responses were activated and partly overlapped with those elicited by the pathogen Pseudomonas syringae DC3000 (Pst). As S.Fr1 is able to mediate plant protective activity against Pst, we tested plant immunity mutants and found that the pattern-recognition co-receptor mutant bak1/bkk1 showed attenuated S.Fr1-dependent plant protection. The experiments demonstrate that the plant responds differently to members of its natural phyllosphere microbiota. A subset of commensals trigger expression of defense-related genes and thereby may contribute to plant health upon pathogen encounter. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

The RpoB H481Y Rifampicin Resistance Mutation and an Active Stringent Response Reduce Virulence and Increase Resistance to Innate Immune Responses in Staphylococcus aureus

PubMed Central

Gao, Wei; Cameron, David R.; Davies, John K.; Kostoulias, Xenia; Stepnell, Justin; Tuck, Kellie L.; Yeaman, Michael R.; Peleg, Anton Y.; Stinear, Timothy P.; Howden, Benjamin P.

2013-01-01

The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H481Y, which is linked to rifampicin resistance, and RelA F128Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure. PMID:23255563

Water deficit modulates the response of Vitis vinifera to the Pierce's disease pathogen Xylella fastidiosa.

PubMed

Choi, Hong-Kyu; Iandolino, Alberto; da Silva, Francisco Goes; Cook, Douglas R

2013-06-01

Pierce's disease, caused by the bacterium Xylella fastidiosa, is one of the most devastating diseases of cultivated grape, currently restricted to the Americas. To test the long-standing hypothesis that Pierce's disease results from pathogen-induced drought stress, we used the Affymetrix Vitis GeneChip to compare the transcriptional response of Vitis vinifera to Xylella infection, water deficit, or a combination of the two stresses. The results reveal a redirection of gene transcription involving 822 genes with a minimum twofold change (P < 0.05), including the upregulation of transcripts for phenylpropanoid and flavonoid biosynthesis, pathogenesis-related proteins, abscisic acid- and jasmonic acid-responsive biosynthesis, and downregulation of transcripts related to photosynthesis, growth, and nutrition. Although the transcriptional response of plants to Xylella infection was largely distinct from the response of healthy plants to water stress, we find that 138 of the pathogen-induced genes exhibited a significantly stronger transcriptional response when plants were simultaneously exposed to infection and drought stress, suggesting a strong interaction between disease and water deficit. This interaction between drought stress and disease was mirrored in planta at the physiological level for aspects of water relations and photosynthesis and in terms of the severity of disease symptoms and the extent of pathogen colonization, providing a molecular correlate of the classical concept of the disease triangle in which environment impacts disease severity.

The expanding universe of hypoxia.

PubMed

Zhang, Huafeng; Semenza, Gregg L

2008-07-01

Reduced oxygen availability (hypoxia) is sensed and transduced into changes in the activity or expression of cellular macromolecules. These responses impact on virtually all areas of biology and medicine. In this meeting report, we summarize major developments in the field that were presented at the 2008 Keystone Symposium on Cellular, Physiological, and Pathogenic Responses to Hypoxia.

Transcriptome dynamics of a susceptible wheat upon Fusarium head blight reveals that molecular responses to Fusarium graminearum infection fit over the grain development processes.

PubMed

Chetouhi, Cherif; Bonhomme, Ludovic; Lasserre-Zuber, Pauline; Cambon, Florence; Pelletier, Sandra; Renou, Jean-Pierre; Langin, Thierry

2016-03-01

In many plant/pathogen interactions, host susceptibility factors are key determinants of disease development promoting pathogen growth and spreading in plant tissues. In the Fusarium head blight (FHB) disease, the molecular basis of wheat susceptibility is still poorly understood while it could provide new insights into the understanding of the wheat/Fusarium graminearum (Fg) interaction and guide future breeding programs to produce cultivars with sustainable resistance. To identify the wheat grain candidate genes, a genome-wide gene expression profiling was performed in the French susceptible wheat cultivar, Recital. Gene-specific two-way ANOVA of about 40 K transcripts at five grain developmental stages identified 1309 differentially expressed genes. Out of these, 536 were impacted by the Fg effect alone. Most of these Fg-responsive genes belonged to biological and molecular functions related to biotic and abiotic stresses indicating the activation of common stress pathways during susceptibility response of wheat grain to FHB. This analysis revealed also 773 other genes displaying either specific Fg-responsive profiles along with grain development stages or synergistic adjustments with the grain development effect. These genes were involved in various molecular pathways including primary metabolism, cell death, and gene expression reprogramming. An increasingly complex host response was revealed, as was the impact of both Fg infection and grain ontogeny on the transcription of wheat genes. This analysis provides a wealth of candidate genes and pathways involved in susceptibility responses to FHB and depicts new clues to the understanding of the susceptibility determinism in plant/pathogen interactions.

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

ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence

PubMed Central

Miyazaki, Taiga; Kohno, Shigeru

2014-01-01

The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence. PMID:24335436

Mevalonate Biosynthesis Intermediates Are Key Regulators of Innate Immunity in Bovine Endometritis

PubMed Central

Collier, Christine; Griffin, Sholeem; Schuberth, Hans-Joachim; Sandra, Olivier; Smith, David G.; Mahan, Suman; Dieuzy-Labaye, Isabelle; Sheldon, I. Martin

2016-01-01

Metabolic changes can influence inflammatory responses to bacteria. To examine whether localized manipulation of the mevalonate pathway impacts innate immunity, we exploited a unique mucosal disease model, endometritis, where inflammation is a consequence of innate immunity. IL responses to pathogenic bacteria and LPS were modulated in bovine endometrial cell and organ cultures by small molecules that target the mevalonate pathway. Treatment with multiple statins, bisphosphonates, squalene synthase inhibitors, and small interfering RNA showed that inhibition of farnesyl-diphosphate farnesyl transferase (squalene synthase), but not 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyl diphosphate synthase, reduced endometrial organ and cellular inflammatory responses to pathogenic bacteria and LPS. Although manipulation of the mevalonate pathway reduced cellular cholesterol, impacts on inflammation were independent of cholesterol concentration as cholesterol depletion using cyclodextrins did not alter inflammatory responses. Treatment with the isoprenoid mevalonate pathway-intermediates, farnesyl diphosphate and geranylgeranyl diphosphate, also reduced endometrial cellular inflammatory responses to LPS. These data imply that manipulating the mevalonate pathway regulates innate immunity within the endometrium, and that isoprenoids are regulatory molecules in this process, knowledge that could be exploited for novel therapeutic strategies. PMID:26673142

The impact of "omic" and imaging technologies on assessing the host immune response to biodefence agents.

PubMed

Tree, Julia A; Flick-Smith, Helen; Elmore, Michael J; Rowland, Caroline A

2014-01-01

Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of "omic" technologies (next generation sequencing, DNA, and protein microarrays) for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy) for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.

Impact of thermal stress on evolutionary trajectories of pathogen resistance in three-spined stickleback (Gasterosteus aculeatus)

PubMed Central

2014-01-01

Background Pathogens are a major regulatory force for host populations, especially under stressful conditions. Elevated temperatures may enhance the development of pathogens, increase the number of transmission stages, and can negatively influence host susceptibility depending on host thermal tolerance. As a net result, this can lead to a higher prevalence of epidemics during summer months. These conditions also apply to marine ecosystems, where possible ecological impacts and the population-specific potential for evolutionary responses to changing environments and increasing disease prevalence are, however, less known. Therefore, we investigated the influence of thermal stress on the evolutionary trajectories of disease resistance in three marine populations of three-spined sticklebacks Gasterosteus aculeatus by combining the effects of elevated temperature and infection with a bacterial strain of Vibrio sp. using a common garden experiment. Results We found that thermal stress had an impact on fish weight and especially on survival after infection after only short periods of thermal acclimation. Environmental stress reduced genetic differentiation (QST) between populations by releasing cryptic within-population variation. While life history traits displayed positive genetic correlations across environments with relatively weak genotype by environment interactions (GxE), environmental stress led to negative genetic correlations across environments in pathogen resistance. This reversal of genetic effects governing resistance is probably attributable to changing environment-dependent virulence mechanisms of the pathogen interacting differently with host genotypes, i.e. GPathogenxGHostxE or (GPathogenxE)x(GHostxE) interactions, rather than to pure host genetic effects, i.e. GHostxE interactions. Conclusion To cope with climatic changes and the associated increase in pathogen virulence, host species require wide thermal tolerances and pathogen-resistant genotypes. The higher resistance we found for some families at elevated temperatures showed that there is evolutionary potential for resistance to Vibrio sp. in both thermal environments. The negative genetic correlation of pathogen resistance between thermal environments, on the other hand, indicates that adaptation to current conditions can be a weak predictor for performance in changing environments. The observed feedback on selective gradients exerted on life history traits may exacerbate this effect, as it can also modify the response to selection for other vital components of fitness. PMID:25927537

Biocontrol of Pathogens in the Meat Chain

NASA Astrophysics Data System (ADS)

Burgess, Catherine M.; Rivas, Lucia; McDonnell, Mary J.; Duffy, Geraldine

Bacterial foodborne zoonotic diseases are of major concern, impacting public health and causing economic losses for the agricultural-food sector and the wider society. In the United States (US) alone foodborne illness from pathogens is responsible for 76 million cases of illnesses each year (Mead et al., 1999). Salmonella, Campylobacter jejuni and Enterohaemorraghic Escherichia coli (EHEC; predominately serotype O157:H7) and Listeria monocytogenes are the most predominant foodborne bacterial pathogens reported in the developed world (United States Department of Agriculture, 2001). The importance of meat and meat products as a vehicle of foodborne zoonotic pathogens cannot be underestimated (Center for Disease Control, 2006; Gillespie, O’Brien, Adak, Cheasty, & Willshaw, 2005; Mazick, Ethelberg, Nielsen, Molbak, & Lisby, 2006; Mead et al., 2006).

Protein phosphatase AP2C1 negatively regulates basal resistance and defense responses to Pseudomonas syringae.

PubMed

Shubchynskyy, Volodymyr; Boniecka, Justyna; Schweighofer, Alois; Simulis, Justinas; Kvederaviciute, Kotryna; Stumpe, Michael; Mauch, Felix; Balazadeh, Salma; Mueller-Roeber, Bernd; Boutrot, Freddy; Zipfel, Cyril; Meskiene, Irute

2017-02-01

Mitogen-activated protein kinases (MAPKs) mediate plant immune responses to pathogenic bacteria. However, less is known about the cell autonomous negative regulatory mechanism controlling basal plant immunity. We report the biological role of Arabidopsis thaliana MAPK phosphatase AP2C1 as a negative regulator of plant basal resistance and defense responses to Pseudomonas syringae. AP2C2, a closely related MAPK phosphatase, also negatively controls plant resistance. Loss of AP2C1 leads to enhanced pathogen-induced MAPK activities, increased callose deposition in response to pathogen-associated molecular patterns or to P. syringae pv. tomato (Pto) DC3000, and enhanced resistance to bacterial infection with Pto. We also reveal the impact of AP2C1 on the global transcriptional reprogramming of transcription factors during Pto infection. Importantly, ap2c1 plants show salicylic acid-independent transcriptional reprogramming of several defense genes and enhanced ethylene production in response to Pto. This study pinpoints the specificity of MAPK regulation by the different MAPK phosphatases AP2C1 and MKP1, which control the same MAPK substrates, nevertheless leading to different downstream events. We suggest that precise and specific control of defined MAPKs by MAPK phosphatases during plant challenge with pathogenic bacteria can strongly influence plant resistance. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response

PubMed Central

Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

2017-01-01

Objective To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. Design We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Results Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. Conclusions We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. PMID:26838600

A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe

PubMed Central

McIntyre, K. Marie; Setzkorn, Christian; Hepworth, Philip J.; Morand, Serge; Morse, Andrew P.; Baylis, Matthew

2014-01-01

Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. PMID:25136810

ANALYSIS OF AQUATIC MICROBIAL COMMUNITIES IMPACTED BY LARGE POULTRY FORMS

EPA Science Inventory

Microbial communities often respond more rapidly and extensively to environmental change than communities of higher organisms. Thus, characterizing shifts in the structure of native bacterial communities as a response to changes in nutrients, antimicrobials, and invading pathogen...

Germline APC mutations in hepatoblastoma.

PubMed

Yang, Adeline; Sisson, Rebecca; Gupta, Anita; Tiao, Greg; Geller, James I

2018-04-01

Conflicting reports on the frequency of germline adenomatous polyposis coli (APC) gene mutations in patients with hepatoblastoma (HB) have called into question the clinical value of APC mutation testing on apparently sporadic HB. An Institutional Review Board approved retrospective review of clinical data collected from patients with HB who received APC testing at our institution was conducted. All HB patients seen at Cincinnati Children's Hospital Medical Center were eligible for testing. Potential genotype/phenotype correlations were assessed. As of July 2015, 29 patients with HB had received constitutional APC testing. Four (14%) were found to have APC pathogenic truncations of the APC protein and in addition two (7%) had APC missense variants of unknown clinical significance. Two patients (7%) had family histories indicative of familial adenomatous polyposis (FAP). Response to chemotherapy tracked differently in APC pathogenic cases, with a slower imaging response despite an equivalent or slightly faster α-fetoprotein (AFP) response. The prevalence of pathogenic APC variants in apparently sporadic HB may be higher than previously detected. Differences in time to imaging response, despite similar AFP response, may impact surgical planning. All patients with HB warrant germline APC mutation testing for underlying FAP. © 2017 Wiley Periodicals, Inc.

Insect-plant-pathogen interactions as shaped by future climate: effects on biology, distribution, and implications for agriculture.

PubMed

Trębicki, Piotr; Dáder, Beatriz; Vassiliadis, Simone; Fereres, Alberto

2017-12-01

Carbon dioxide (CO 2 ) is the main anthropogenic gas which has drastically increased since the industrial revolution, and current concentrations are projected to double by the end of this century. As a consequence, elevated CO 2 is expected to alter the earths' climate, increase global temperatures and change weather patterns. This is likely to have both direct and indirect impacts on plants, insect pests, plant pathogens and their distribution, and is therefore problematic for the security of future food production. This review summarizes the latest findings and highlights current knowledge gaps regarding the influence of climate change on insect, plant and pathogen interactions with an emphasis on agriculture and food production. Direct effects of climate change, including increased CO 2 concentration, temperature, patterns of rainfall and severe weather events that impact insects (namely vectors of plant pathogens) are discussed. Elevated CO 2 and temperature, together with plant pathogen infection, can considerably change plant biochemistry and therefore plant defense responses. This can have substantial consequences on insect fecundity, feeding rates, survival, population size, and dispersal. Generally, changes in host plant quality due to elevated CO 2 (e.g., carbon to nitrogen ratios in C3 plants) negatively affect insect pests. However, compensatory feeding, increased population size and distribution have also been reported for some agricultural insect pests. This underlines the importance of additional research on more targeted, individual insect-plant scenarios at specific locations to fully understand the impact of a changing climate on insect-plant-pathogen interactions. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Assessing the consequences of global change for forest disturbance from herbivores and pathogens.

PubMed

Ayres, M P; Lombardero, M J

2000-11-15

Herbivores and pathogens impact the species composition, ecosystem function, and socioeconomic value of forests. Herbivores and pathogens are an integral part of forests, but sometimes produce undesirable effects and a degradation of forest resources. In the United States, a few species of forest pests routinely have significant impacts on up to 20 million ha of forest with economic costs that probably exceed $1 billion/year. Climatic change could alter patterns of disturbance from herbivores and pathogens through: (1) direct effects on the development and survival of herbivores and pathogens; (2) physiological changes in tree defenses; and (3) indirect effects from changes in the abundance of natural enemies (e.g. parasitoids of insect herbivores), mutualists (e.g. insect vectors of tree pathogens), and competitors. Because of their short life cycles, mobility, reproductive potential, and physiological sensitivity to temperature, even modest climate change will have rapid impacts on the distribution and abundance of many forest insects and pathogens. We identify 32 syndromes of biotic disturbance in North American forests that should be carefully evaluated for their responses to climate change: 15 insect herbivores, browsing mammals; 12 pathogens; 1 plant parasite; and 3 undiagnosed patterns of forest decline. It is probable that climatic effects on some herbivores and pathogens will impact on biodiversity, recreation, property value, forest industry, and even water quality. Some scenarios are beneficial (e.g. decreased snow cover may increase winter mortality of some insect pests), but many are detrimental (e.g. warming tends to accelerate insect development rate and facilitate range expansions of pests and climate change tends to produce a mismatch between mature trees and their environment, which can increase vulnerability to herbivores and pathogens). Changes in forest disturbance can produce feedback to climate through affects on water and carbon flux in forest ecosystems; one alarming scenario is that climate warming may increase insect outbreaks in boreal forests, which would tend to increase forest fires and exacerbate further climate warming by releasing carbon stores from boreal ecosystems. We suggest a list of research priorities that will allow us to refine these risk assessments and adopt forest management strategies that anticipate changes in biotic disturbance regimes and mitigate the ecological, social, and economic risks.

Network Analysis Reveals a Common Host-Pathogen Interaction Pattern in Arabidopsis Immune Responses.

PubMed

Li, Hong; Zhou, Yuan; Zhang, Ziding

2017-01-01

Many plant pathogens secrete virulence effectors into host cells to target important proteins in host cellular network. However, the dynamic interactions between effectors and host cellular network have not been fully understood. Here, an integrative network analysis was conducted by combining Arabidopsis thaliana protein-protein interaction network, known targets of Pseudomonas syringae and Hyaloperonospora arabidopsidis effectors, and gene expression profiles in the immune response. In particular, we focused on the characteristic network topology of the effector targets and differentially expressed genes (DEGs). We found that effectors tended to manipulate key network positions with higher betweenness centrality. The effector targets, especially those that are common targets of an individual effector, tended to be clustered together in the network. Moreover, the distances between the effector targets and DEGs increased over time during infection. In line with this observation, pathogen-susceptible mutants tended to have more DEGs surrounding the effector targets compared with resistant mutants. Our results suggest a common plant-pathogen interaction pattern at the cellular network level, where pathogens employ potent local impact mode to interfere with key positions in the host network, and plant organizes an in-depth defense by sequentially activating genes distal to the effector targets.

The RpoB H₄₈₁Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus.

PubMed

Gao, Wei; Cameron, David R; Davies, John K; Kostoulias, Xenia; Stepnell, Justin; Tuck, Kellie L; Yeaman, Michael R; Peleg, Anton Y; Stinear, Timothy P; Howden, Benjamin P

2013-03-15

The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H₄₈₁Y, which is linked to rifampicin resistance, and RelA F₁₂₈Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure.

Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response.

PubMed

Rodriguez, Stéphane; Roussel, Mikaël; Tarte, Karin; Amé-Thomas, Patricia

2017-01-01

During the last decades, considerable efforts have been done to decipher mechanisms supported by microorganisms or viruses involved in the development, differentiation, and function of immune cells. Pathogens and their associated secretome as well as the continuous inflammation observed in chronic infection are shaping both innate and adaptive immunity. Secondary lymphoid organs are functional structures ensuring the mounting of adaptive immune response against microorganisms and viruses. Inside these organs, germinal centers (GCs) are the specialized sites where mature B-cell differentiation occurs leading to the release of high-affinity immunoglobulin (Ig)-secreting cells. Different steps are critical to complete B-cell differentiation process, including proliferation, somatic hypermutations in Ig variable genes, affinity-based selection, and class switch recombination. All these steps require intense interactions with cognate CD4 + helper T cells belonging to follicular helper lineage. Interestingly, pathogens can disturb this subtle machinery affecting the classical adaptive immune response. In this review, we describe how viruses could act directly on GC B cells, either through B-cell infection or by their contribution to B-cell cancer development and maintenance. In addition, we depict the indirect impact of viruses on B-cell response through infection of GC T cells and stromal cells, leading to immune response modulation.

Effects of biotic disturbances on forest carbon cycling in the United States and Canada

USGS Publications Warehouse

Vogelmann, James E.; Allen, Craig D.; Hicke, Jeffrey A.; Desai, Ankur R.; Dietze, Michael C.; Hall, Ronald J.; ,

2012-01-01

Forest insects and pathogens are major disturbance agents that have affected millions of hectares in North America in recent decades, implying significant impacts to the carbon (C) cycle. Here, we review and synthesize published studies of the effects of biotic disturbances on forest C cycling in the United States and Canada. Primary productivity in stands was reduced, sometimes considerably, immediately following insect or pathogen attack. After repeated growth reductions caused by some insects or pathogens or a single infestation by some bark beetle species, tree mortality occurred, altering productivity and decomposition. In the years following disturbance, primary productivity in some cases increased rapidly as a result of enhanced growth by surviving vegetation, and in other cases increased slowly because of lower forest regrowth. In the decades following tree mortality, decomposition increased as a result of the large amount of dead organic matter. Net ecosystem productivity decreased immediately following attack, with some studies reporting a switch to a C source to the atmosphere, and increased afterward as the forest regrew and dead organic matter decomposed. Large variability in C cycle responses arose from several factors, including type of insect or pathogen, time since disturbance, number of trees affected, and capacity of remaining vegetation to increase growth rates following outbreak. We identified significant knowledge gaps, including limited understanding of carbon cycle impacts among different biotic disturbance types (particularly pathogens), their impacts at landscape and regional scales, and limited capacity to predict disturbance events and their consequences for carbon cycling. We conclude that biotic disturbances can have major impacts on forest C stocks and fluxes and can be large enough to affect regional C cycling. However, additional research is needed to reduce the uncertainties associated with quantifying biotic disturbance effects on the North American C budget.

'Order from disorder sprung': recognition and regulation in the immune system

NASA Astrophysics Data System (ADS)

Mak, Tak W.

2003-06-01

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

'Order from disorder sprung': recognition and regulation in the immune system.

PubMed

Mak, Tak W

2003-06-15

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

The Evolution of Host Mitochondrial Association and its Impact on Toxoplasma gondii Infection

NASA Astrophysics Data System (ADS)

English, Elizabeth D.

The association of intracellular pathogens with host mitochondria has been observed across taxa, from bacterial pathogens, such as Legionella pneumophila and Chlamydia trachomati, to the eukaryotic pathogen Toxoplasma gondii. However the functional impact of host mitochondrial association (HMA) remains difficult to assess in most of these species because in many cases the genes responsible for this phenomenon have not yet been identified. The recent discovery of the T. gondii gene responsible for HMA, Mitochondrial Association Factor 1 ( MAF1) has provided us with the tools to begin to understand the evolution and impact of HMA. Here we use multispecies sequence analysis to determine that the MAF1 locus is tandemly duplicated and diversified in both T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative Neospora caninum. Using cross-species complementation we find that T. gondii and H. hammondi harbor copies of MAF1 able to mediate HMA, while N. caninum does not. We have begun mutational analysis using naturally occurring HMA+ and HMA- paralogs of MAF1 in order to determine the portions of MAF1 protein necessary for HMA. Additionally, we have identified the first in vivo phenotypes associated with HMA using multiple mouse models, for both acute and chronic infection. Taken together these data indicate that HMA likely evolved via neofunctionalization of a duplicated ancestral MAF1 gene, and that the neofunctionalized, HMA competent copy of MAF1 provides a selective advantage.

Transposable Elements as Stress Adaptive Capacitors Induce Genomic Instability in Fungal Pathogen Magnaporthe oryzae

PubMed Central

Chadha, Sonia; Sharma, Mradul

2014-01-01

A fundamental problem in fungal pathogenesis is to elucidate the evolutionary forces responsible for genomic rearrangements leading to races with fitter genotypes. Understanding the adaptive evolutionary mechanisms requires identification of genomic components and environmental factors reshaping the genome of fungal pathogens to adapt. Herein, Magnaporthe oryzae, a model fungal plant pathogen is used to demonstrate the impact of environmental cues on transposable elements (TE) based genome dynamics. For heat shock and copper stress exposed samples, eight TEs belonging to class I and II family were employed to obtain DNA profiles. Stress induced mutant bands showed a positive correlation with dose/duration of stress and provided evidences of TEs role in stress adaptiveness. Further, we demonstrate that genome dynamics differ for the type/family of TEs upon stress exposition and previous reports of stress induced MAGGY transposition has underestimated the role of TEs in M. oryzae. Here, we identified Pyret, MAGGY, Pot3, MINE, Mg-SINE, Grasshopper and MGLR3 as contributors of high genomic instability in M. oryzae in respective order. Sequencing of mutated bands led to the identification of LTR-retrotransposon sequences within regulatory regions of psuedogenes. DNA transposon Pot3 was identified in the coding regions of chromatin remodelling protein containing tyrosinase copper-binding and PWWP domains. LTR-retrotransposons Pyret and MAGGY are identified as key components responsible for the high genomic instability and perhaps these TEs are utilized by M. oryzae for its acclimatization to adverse environmental conditions. Our results demonstrate how common field stresses change genome dynamics of pathogen and provide perspective to explore the role of TEs in genome adaptability, signalling network and its impact on the virulence of fungal pathogens. PMID:24709911

Bifidobacterium breve UCC2003 surface exopolysaccharide production is a beneficial trait mediating commensal-host interaction through immune modulation and pathogen protection.

PubMed

Fanning, Saranna; Hall, Lindsay J; van Sinderen, Douwe

2012-01-01

Bifidobacteria constitute a substantial proportion of the human gut microbiota. There are currently many bifidobacterial strains with claimed probiotic attributes. The mechanism through which these strains reside within their host and exert benefits to the host is far from fully understood. We have shown in the case of Bifidobacterium breve UCC2003 that a cell surface exopolysaccharide (EPS) plays a role in in vivo persistence. Biosynthesis of two possible EPSs is controlled by a bidirectional gene cluster which guides alternate EPS synthesis by means of a reorienting promoter. The presence of EPS impacts on host immune response: the wild type, EPS-positive B. breve UCC2003 efficiently evades the adaptive B-cell host response, while its isogenic, EPS-deficient equivalent elicits a strong adaptive immune response. Functionally, EPS positive strains were more resilient to presence of acid and bile and were responsible for reduced colonization levels of Citrobacter rodentium, a gut pathogen. In conclusion, we have found that EPS is important in host interactions and pathogen protection, the latter indicative of a probiotic ability for the EPS of B. breve UCC2003.

Host-pathogen interplay at primary infection sites in pigs challenged with Actinobacillus pleuropneumoniae.

PubMed

Sassu, Elena L; Frömbling, Janna; Duvigneau, J Catharina; Miller, Ingrid; Müllebner, Andrea; Gutiérrez, Ana M; Grunert, Tom; Patzl, Martina; Saalmüller, Armin; von Altrock, Alexandra; Menzel, Anne; Ganter, Martin; Spergser, Joachim; Hewicker-Trautwein, Marion; Verspohl, Jutta; Ehling-Schulz, Monika; Hennig-Pauka, Isabel

2017-02-28

Actinobacillus (A.) pleuropneumoniae is the causative agent of porcine pleuropneumonia and causes significant losses in the pig industry worldwide. Early host immune response is crucial for further progression of the disease. A. pleuropneumoniae is either rapidly eliminated by the immune system or switches to a long-term persistent form. To gain insight into the host-pathogen interaction during the early stages of infection, pigs were inoculated intratracheally with A. pleuropneumoniae serotype 2 and humanely euthanized eight hours after infection. Gene expression studies of inflammatory cytokines and the acute phase proteins haptoglobin, serum amyloid A and C-reactive protein were carried out by RT-qPCR from the lung, liver, tonsils and salivary gland. In addition, the concentration of cytokines and acute phase proteins were measured by quantitative immunoassays in bronchoalveolar lavage fluid, serum and saliva. In parallel to the analyses of host response, the impact of the host on the bacterial pathogen was assessed on a metabolic level. For the latter, Fourier-Transform Infrared (FTIR-) spectroscopy was employed. Significant cytokine and acute phase protein gene expression was detected in the lung and the salivary gland however this was not observed in the tonsils. In parallel to the analyses of host response, the impact of the host on the bacterial pathogen was assessed on a metabolic level. For the latter investigations, Fourier-Transform Infrared (FTIR-) spectroscopy was employed. The bacteria isolated from the upper and lower respiratory tract showed distinct IR spectral patterns reflecting the organ-specific acute phase response of the host. In summary, this study implies a metabolic adaptation of A. pleuropneumoniae to the porcine upper respiratory tract already during early infection, which might indicate a first step towards the persistence of A. pleuropneumoniae. Not only in lung, but also in the salivary gland an increased inflammatory gene expression was detectable during the acute stage of infection.

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

PubMed Central

de la Fuente, José; Antunes, Sandra; Bonnet, Sarah; Cabezas-Cruz, Alejandro; Domingos, Ana G.; Estrada-Peña, Agustín; Johnson, Nicholas; Kocan, Katherine M.; Mansfield, Karen L.; Nijhof, Ard M.; Papa, Anna; Rudenko, Nataliia; Villar, Margarita; Alberdi, Pilar; Torina, Alessandra; Ayllón, Nieves; Vancova, Marie; Golovchenko, Maryna; Grubhoffer, Libor; Caracappa, Santo; Fooks, Anthony R.; Gortazar, Christian; Rego, Ryan O. M.

2017-01-01

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases. PMID:28439499

Development of a dual vaccine for prevention of Brucella abortus infection and Escherichia coli O157:H7 intestinal colonization.

PubMed

Iannino, Florencia; Herrmann, Claudia K; Roset, Mara S; Briones, Gabriel

2015-05-05

Zoonoses that affect human and animal health have an important economic impact. In the study now presented, a bivalent vaccine has been developed that has the potential for preventing the transmission from cattle to humans of two bacterial pathogens: Brucella abortus and Shiga toxin-producing Escherichia coli (STEC). A 66kDa chimeric antigen, composed by EspA, Intimin, Tir, and H7 flagellin (EITH7) from STEC, was constructed and expressed in B. abortus Δpgm vaccine strain (BabΔpgm). Mice orally immunized with BabΔpgm(EITH7) elicited an immune response with the induction of anti-EITH7 antibodies (IgA) that clears an intestinal infection of E. coli O157:H7 three times faster (t=4 days) than mice immunized with BabΔpgm carrier strain (t=12 days). As expected, mice immunized with BabΔpgm(EITH7) strain also elicited a protective immune response against B. abortus infection. A Brucella-based vaccine platform is described capable of eliciting a combined protective immune response against two bacterial pathogens with diverse lifestyles-the intracellular pathogen B. abortus and the intestinal extracellular pathogen STEC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plant Microbe Interactions in Post Genomic Era: Perspectives and Applications

PubMed Central

Imam, Jahangir; Singh, Puneet K.; Shukla, Pratyoosh

2016-01-01

Deciphering plant–microbe interactions is a promising aspect to understand the benefits and the pathogenic effect of microbes and crop improvement. The advancement in sequencing technologies and various ‘omics’ tool has impressively accelerated the research in biological sciences in this area. The recent and ongoing developments provide a unique approach to describing these intricate interactions and test hypotheses. In the present review, we discuss the role of plant-pathogen interaction in crop improvement. The plant innate immunity has always been an important aspect of research and leads to some interesting information like the adaptation of unique immune mechanisms of plants against pathogens. The development of new techniques in the post - genomic era has greatly enhanced our understanding of the regulation of plant defense mechanisms against pathogens. The present review also provides an overview of beneficial plant–microbe interactions with special reference to Agrobacterium tumefaciens-plant interactions where plant derived signal molecules and plant immune responses are important in pathogenicity and transformation efficiency. The construction of various Genome-scale metabolic models of microorganisms and plants presented a better understanding of all metabolic interactions activated during the interactions. This review also lists the emerging repertoire of phytopathogens and its impact on plant disease resistance. Outline of different aspects of plant-pathogen interactions is presented in this review to bridge the gap between plant microbial ecology and their immune responses. PMID:27725809

The impacts of lignin modifications on fungal pathogen and insect interactions in sorghum

USDA-ARS?s Scientific Manuscript database

Sorghum (Sorghum bicolor (L.) Moench) is currently being developed as a dedicated bioenergy feedstock. Modifying lignin content and composition are major targets for bioenergy feedstock improvement. However, lignin has long been implicated as playing a critical role in plant defense responses agains...

Antigenic variability: Obstacles on the road to vaccines against traditionally difficult targets.

PubMed

Servín-Blanco, R; Zamora-Alvarado, R; Gevorkian, G; Manoutcharian, K

2016-10-02

Despite the impressive impact of vaccines on public health, the success of vaccines targeting many important pathogens and cancers has to date been limited. The burden of infectious diseases today is mainly caused by antigenically variable pathogens (AVPs), which escape immune responses induced by prior infection or vaccination through changes in molecular structures recognized by antibodies or T cells. Extensive genetic and antigenic variability is the major obstacle for the development of new or improved vaccines against "difficult" targets. Alternative, qualitatively new approaches leading to the generation of disease- and patient-specific vaccine immunogens that incorporate complex permanently changing epitope landscapes of intended targets accompanied by appropriate immunomodulators are urgently needed. In this review, we highlight some of the most critical common issues related to the development of vaccines against many pathogens and cancers that escape protective immune responses owing to antigenic variation, and discuss recent efforts to overcome the obstacles by applying alternative approaches for the rational design of new types of immunogens.

Allergic Responses Induced by a Fungal Biopesticide Metarhizium anisopliae and House Dust Mite are Compared in a Mouse Model

EPA Science Inventory

Biopesticides can be effective in controlling their target pest. However, research regarding mammalian health impacts of these agents has focused on toxicity and pathogenicity, with limited research regarding allergenicity and asthma development. We compared the ability of funga...

Agreement between quantitative microbial risk assessment and epidemiology at low doses during waterborne outbreaks of protozoan disease

USDA-ARS?s Scientific Manuscript database

Quantitative microbial risk assessment (QMRA) is a valuable complement to epidemiology for understanding the health impacts of waterborne pathogens. The approach works by extrapolating available data in two ways. First, dose-response data are typically extrapolated from feeding studies, which use ...

Neutral Theory and Rapidly Evolving Viral Pathogens.

PubMed

Frost, Simon D W; Magalis, Brittany Rife; Kosakovsky Pond, Sergei L

2018-06-01

The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.

Imidacloprid intensifies its impact on honeybee and bumblebee cellular immune response when challenged with LPS (lippopolysacharide) of Escherichia coli.

PubMed

Walderdorff, Louise; Laval-Gilly, Philippe; Bonnefoy, Antoine; Falla-Angel, Jaïro

2018-07-01

Insect hemocytes play an important role in insects' defense against environmental stressors as they are entirely dependent on their innate immune system for pathogen defense. In recent years a dramatic decline of pollinators has been reported in many countries. The drivers of this declines appear to be associated with pathogen infections like viruses, bacteria or fungi in combination with pesticide exposure. The aim of this study was thus to investigate the impact of imidacloprid, a neonicotinoid insecticide, on the cellular immune response of two pollinators (Apis mellifera and Bombus terrestris) during simultaneous immune activation with LPS (lipopolysaccharide) of Escherichia coli. For this purpose the phagocytosis capacity as well as the production of H 2 O 2 and NO of larval hemocytes, exposed to five different imidacloprid concentrations in vitro, was measured. All used pesticide concentrations showed a weakening effect on phagocytosis with but also without LPS activation. Imidacloprid decreased H 2 O 2 and increased NO production in honeybees. Immune activation by LPS clearly reinforced the effect of imidacloprid on the immune response of hemocytes in all three immune parameters tested. Bumblebee hemocytes appeared more sensitive to imidacloprid during phagocytosis assays while imidacloprid showed a greater impact on honeybee hemocytes during H 2 O 2 and NO production. Copyright © 2018 Elsevier Ltd. All rights reserved.

Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.

PubMed

Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

2017-05-01

To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis ( Pg ), Fusobacterium nucleatum and Prevotella intermedia . The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Regulation of H2O2 stress-responsive genes through a novel transcription factor in the protozoan pathogen Entamoeba histolytica.

PubMed

Pearson, Richard J; Morf, Laura; Singh, Upinder

2013-02-08

Outcome of infection depends upon complex interactions between the invading pathogen and the host. As part of the host's innate immune response, the release of reactive oxygen and nitrogen species by phagocytes represents a major obstacle to the establishment of infection. The ability of the human parasite Entamoeba histolytica to survive reactive oxygen and nitrogen species is central to its pathogenic potential and contributes to disease outcome. In order to define the transcriptional network associated with oxidative stress, we utilized the MEME and MAST programs to analyze the promoter regions of 57 amoebic genes that had increased expression specifically in response to H(2)O(2) exposure. We functionally characterized an H(2)O(2)-regulatory motif (HRM) ((1)AAACCTCAATGAAGA(15)), which was enriched in these promoters and specifically bound amoebic nuclear protein(s). Assays with promoter-luciferase fusions established the importance of key residues and that the HRM motif directly impacted the ability of H(2)O(2)-responsive promoters to drive gene expression. DNA affinity chromatography and mass spectrometry identified EHI_108720 as an HRM DNA-binding protein. Overexpression and down-regulation of EHI_108720 demonstrated the specificity of EHI_108720 protein binding to the HRM, and overexpression increased basal expression from an H(2)O(2)-responsive wild-type promoter but not from its mutant counterpart. Thus, EHI_108720, or HRM-binding protein, represents a new stress-responsive transcription factor in E. histolytica that controls a transcriptional regulatory network associated with oxidative stress. Overexpression of EHI_108720 increased parasite virulence. Insight into how E. histolytica responds to oxidative stress increases our understanding of how this important human pathogen establishes invasive disease.

Regulation of H2O2 Stress-responsive Genes through a Novel Transcription Factor in the Protozoan Pathogen Entamoeba histolytica*

PubMed Central

Pearson, Richard J.; Morf, Laura; Singh, Upinder

2013-01-01

Outcome of infection depends upon complex interactions between the invading pathogen and the host. As part of the host's innate immune response, the release of reactive oxygen and nitrogen species by phagocytes represents a major obstacle to the establishment of infection. The ability of the human parasite Entamoeba histolytica to survive reactive oxygen and nitrogen species is central to its pathogenic potential and contributes to disease outcome. In order to define the transcriptional network associated with oxidative stress, we utilized the MEME and MAST programs to analyze the promoter regions of 57 amoebic genes that had increased expression specifically in response to H2O2 exposure. We functionally characterized an H2O2-regulatory motif (HRM) (1AAACCTCAATGAAGA15), which was enriched in these promoters and specifically bound amoebic nuclear protein(s). Assays with promoter-luciferase fusions established the importance of key residues and that the HRM motif directly impacted the ability of H2O2-responsive promoters to drive gene expression. DNA affinity chromatography and mass spectrometry identified EHI_108720 as an HRM DNA-binding protein. Overexpression and down-regulation of EHI_108720 demonstrated the specificity of EHI_108720 protein binding to the HRM, and overexpression increased basal expression from an H2O2-responsive wild-type promoter but not from its mutant counterpart. Thus, EHI_108720, or HRM-binding protein, represents a new stress-responsive transcription factor in E. histolytica that controls a transcriptional regulatory network associated with oxidative stress. Overexpression of EHI_108720 increased parasite virulence. Insight into how E. histolytica responds to oxidative stress increases our understanding of how this important human pathogen establishes invasive disease. PMID:23250742

Reducing the risk of invasive forest pests and pathogens: Combining legislation, targeted management and public awareness.

PubMed

Klapwijk, Maartje J; Hopkins, Anna J M; Eriksson, Louise; Pettersson, Maria; Schroeder, Martin; Lindelöw, Åke; Rönnberg, Jonas; Keskitalo, E Carina H; Kenis, Marc

2016-02-01

Intensifying global trade will result in increased numbers of plant pest and pathogen species inadvertently being transported along with cargo. This paper examines current mechanisms for prevention and management of potential introductions of forest insect pests and pathogens in the European Union (EU). Current European legislation has not been found sufficient in preventing invasion, establishment and spread of pest and pathogen species within the EU. Costs associated with future invasions are difficult to estimate but past invasions have led to negative economic impacts in the invaded country. The challenge is combining free trade and free movement of products (within the EU) with protection against invasive pests and pathogens. Public awareness may mobilise the public for prevention and detection of potential invasions and, simultaneously, increase support for eradication and control measures. We recommend focus on commodities in addition to pathways, an approach within the EU using a centralised response unit and, critically, to engage the general public in the battle against establishment and spread of these harmful pests and pathogens.

Pathogen stimulation history impacts donor-specific CD8+ T cell susceptibility to costimulation/integrin blockade-based therapy

PubMed Central

Badell, IR; Kitchens, WH; Wagener, ME; Lukacher, AE; Larsen, CP; Ford, ML

2017-01-01

Recent studies have shown that the quantity of donor-reactive memory T cells is an important factor in determining the relative heterologous immunity barrier posed during transplantation. Here, we hypothesized that the quality of T cell memory also potently influences the response to costimulation blockade-based immunosuppression. Using a murine skin graft model of CD8+ memory T cell-mediated costimulation blockade resistance, we elicited donor-reactive memory T cells using three distinct types of pathogen infections. Strikingly, we observed differential efficacy of a costimulation and integrin blockade regimen based on the type of pathogen used to elicit the donor-reactive memory T cell response. Intriguingly, the most immunosuppression-sensitive memory T cell populations were composed primarily of central memory cells that possessed greater recall potential, exhibited a less differentiated phenotype, and contained more multi-cytokine producers. These data therefore demonstrate that the memory T cell barrier is dependent on the specific type of pathogen infection via which the donor-reactive memory T cells are elicited, and suggest that the immune stimulation history of a given transplant patient may profoundly influence the relative barrier posed by heterologous immunity during transplantation. PMID:26228897

Progress and challenges in implementing the research on ESKAPE pathogens.

PubMed

Rice, Louis B

2010-11-01

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are responsible for a substantial percentage of nosocomial infections in the modern hospital and represent the vast majority of isolates whose resistance to antimicrobial agents presents serious therapeutic dilemmas for physicians. Over the years, improved molecular biology techniques have led to detailed information about individual resistance mechanisms in all these pathogens. However, there remains a lack of compelling data on the interplay between resistance mechanisms and between the bacteria themselves. In addition, data on the impact of clinical interventions to decrease the prevalence of resistance are also lacking. The difficulty in identifying novel antimicrobial agents with reliable activity against these pathogens argues for an augmentation of research in the basic and population science of resistance, as well as careful studies to identify optimal strategies for infection control and antimicrobial use.

The race between infection and immunity - how do pathogens set the pace?

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

Ribiero, Ruy M

2009-01-01

Infection is often referred to as a race between pathogen and immune response. This metaphor suggests that slower growing pathogens should be more easily controlled. However, a growing body ofevidence shows that many chronic infections are caused by failure to control slow growing pathogens. The slow growth of pathogens appears to directly affect the kinetics of the immune response. Compared with the response to fast growing pathogens, the T cell response to slow pathogens is delayed in its initiation, lymphocyte expansion is slow and the response often fails to clear the pathogen, leading to chronic infection. Understanding the 'rules ofthemore » race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections.« less

Lack of broad functional differences in immunity in fully vaccinated vs. unvaccinated children.

PubMed

Sherrid, Ashley M; Ruck, Candice E; Sutherland, Darren; Cai, Bing; Kollmann, Tobias R

2017-04-01

Concerns have been raised that with an increase in the number of vaccines administered early in life, immune development could be altered, leading to either increased or decreased immune reactivity. We investigated the impact of vaccination on immune status, contrasting the immune response to general, nonantigen-specific stimuli in a cohort of entirely unvaccinated vs. fully vaccinated children at 3-5 y of age. Innate immunity was assessed by quantifying bulk and cell-type-specific cytokine production in response to stimulation with pathogen associated microbial patterns. Adaptive immune status was characterized by assessing lymphocyte proliferation and cytokine production in response to generic T cell stimuli. Our investigations failed to reveal a broadly evident alteration of either innate or adaptive immunity in vaccinated children. Equivalently robust innate and adaptive responses to pathogen associated microbial patterns and generic T cell stimulants were observed in both groups. Although our sample size was small, our data suggest that standard childhood vaccinations do not lead to long-lasting gross alterations of the immune system.

The varieties of immunological experience: of pathogens, stress, and dendritic cells.

PubMed

Pulendran, Bali

2015-01-01

In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.

An INCA model for pathogens in rivers and catchments: Model structure, sensitivity analysis and application to the River Thames catchment, UK.

PubMed

Whitehead, P G; Leckie, H; Rankinen, K; Butterfield, D; Futter, M N; Bussi, G

2016-12-01

Pathogens are an ongoing issue for catchment water management and quantifying their transport, loss and potential impacts at key locations, such as water abstractions for public supply and bathing sites, is an important aspect of catchment and coastal management. The Integrated Catchment Model (INCA) has been adapted to model the sources and sinks of pathogens and to capture the dominant dynamics and processes controlling pathogens in catchments. The model simulates the stores of pathogens in soils, sediments, rivers and groundwaters and can account for diffuse inputs of pathogens from agriculture, urban areas or atmospheric deposition. The model also allows for point source discharges from intensive livestock units or from sewage treatment works or any industrial input to river systems. Model equations are presented and the new pathogens model has been applied to the River Thames in order to assess total coliform (TC) responses under current and projected future land use. A Monte Carlo sensitivity analysis indicates that the input coliform estimates from agricultural sources and decay rates are the crucial parameters controlling pathogen behaviour. Whilst there are a number of uncertainties associated with the model that should be accounted for, INCA-Pathogens potentially provides a useful tool to inform policy decisions and manage pathogen loading in river systems. Copyright © 2016. Published by Elsevier B.V.

The role of social cognition in parasite and pathogen avoidance.

PubMed

Kavaliers, Martin; Choleris, Elena

2018-07-19

The acquisition and use of social information are integral to social behaviour and parasite/pathogen avoidance. This involves social cognition which encompasses mechanisms for acquiring, processing, retaining and acting on social information. Social cognition entails the acquisition of social information about others (i.e. social recognition) and from others (i.e. social learning). Social cognition involves assessing other individuals and their infection status and the pathogen and parasite threat they pose and deciding about when and how to interact with them. Social cognition provides a framework for examining pathogen and parasite avoidance behaviours and their associated neurobiological mechanisms. Here, we briefly consider the relationships between social cognition and olfactory-mediated pathogen and parasite avoidance behaviours. We briefly discuss aspects of (i) social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on mate and social partner choice; (ii) the roles of 'out-groups' (strangers, unfamiliar individuals) and 'in-groups' (familiar individuals) in the expression of parasite/pathogen avoidance behaviours; (iii) individual and social learning, i.e. the utilization of the pathogen recognition and avoidance responses of others; and (iv) the neurobiological mechanisms, in particular the roles of the nonapeptide, oxytocin and steroid hormones (oestrogens) associated with social cognition and parasite/pathogen avoidance.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'. © 2018 The Author(s).

Conservation and restoration of forest trees impacted by non-native pathogens: the role of genetics and tree improvement

Treesearch

R.A. Sniezko; L.A. Winn

2017-01-01

North American native tree species in forest ecosystems, as well as managed forests and urban plantings, are being severely impacted by pathogens and insects. The impacts of these pathogens and insects often increase over time, and they are particularly acute for those species affected by non-native pathogens and insects. For restoration of affected tree species or for...

Why, when and how should exposure be considered at the within-host scale? A modelling contribution to PRRSv infection.

PubMed

Go, Natacha; Belloc, Catherine; Bidot, Caroline; Touzeau, Suzanne

2018-05-21

Understanding the impact of pathogen exposure on the within-host dynamics and its outcome in terms of infectiousness is a key issue to better understand and control the infection spread. Most experimental and modelling studies tackling this issue looked at the impact of the exposure dose on the infection probability and pathogen load, very few on the within-host immune response. Our aim was to explore the impact on the within-host response not only of the exposure dose, but also of its duration and peak, for contrasted virulence levels. We used an integrative modelling approach of the within-host dynamics at the between-cell level. We focused on the porcine reproductive and respiratory syndrome virus, a major concern for the swine industry. We quantified the impact of exposure and virulence on the viral dynamics and immune response by global sensitivity analyses and descriptive statistics. We found that the area under the viral curve, an indicator of the infection severity, was fully determined by the exposure intensity. The infection duration increased with the strain virulence and, for a given strain, exhibited a positive linear correlation with the exposure intensity logarithm and the exposure duration. Taking into account the exposure intensity is hence necessary. Besides, representing the exposure due to contacts by a single punctual dose would tend to underestimate the infection duration. As the infection severity and duration both contribute to the pig infectiousness, a prolonged exposure of the adequate intensity would be recommended in an immuno-epidemiological context.

Common and uncommon pathogenic cascades in lysosomal storage diseases.

PubMed

Vitner, Einat B; Platt, Frances M; Futerman, Anthony H

2010-07-02

Lysosomal storage diseases (LSDs), of which about 50 are known, are caused by the defective activity of lysosomal proteins, resulting in accumulation of unmetabolized substrates. As a result, a variety of pathogenic cascades are activated such as altered calcium homeostasis, oxidative stress, inflammation, altered lipid trafficking, autophagy, endoplasmic reticulum stress, and autoimmune responses. Some of these pathways are common to many LSDs, whereas others are only altered in a subset of LSDs. We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches.

Climate change: effects on animal disease systems and implications for surveillance and control.

PubMed

de La Rocque, S; Rioux, J A; Slingenbergh, J

2008-08-01

Climate driven and other changes in landscape structure and texture, plus more general factors, may create favourable ecological niches for emerging diseases. Abiotic factors impact on vectors, reservoirs and pathogen bionomics and their ability to establish in new ecosystems. Changes in climatic patterns and in seasonal conditions may affect disease behaviour in terms of spread pattern, diffusion range, amplification and persistence in novel habitats. Pathogen invasion may result in the emergence of novel disease complexes, presenting major challenges for the sustainability of future animal agriculture at the global level. In this paper, some of the ecological mechanisms underlying the impact of climatic change on disease transmission and disease spread are further described. Potential effects of different climatic variables on pathogens and host population dynamics and distribution are complex to assess, and different approaches are used to describe the underlying epidemiological processes and the availability of ecological niches for pathogens and vectors. The invasion process can disrupt the long-term co-evolution of species. Pathogens adhering to an r-type strategy (e.g. RNA viruses) may be more inclined to encroach on a novel niche resulting from climate change. However, even when linkage between disease dynamics and climate change are relatively strong, there are other factors changing disease behaviour, and these should be accounted for as well. Overall vulnerability of a given ecosystem is a key variable in this regard. The impact of climate-driven changes varies in different parts of the world and in the different agro-climatic zones. Perhaps priority should go to those geographical areas where the integrity of the ecosystem is most severely affected and the adaptability, in terms of robustness and sustainability of response, relatively low.

a-Copaene and quercivorol lures: Chemical analysis and efficacy for detection of Euwallacea nr. fornicatus (Coleoptera: Curculionidae: Scolytinae)

USDA-ARS?s Scientific Manuscript database

Invasive ambrosia beetles in the Euwallacea nr. fornicatus complex vector a fungal pathogen responsible for Fusarium dieback, a disease that impacts avocado (Persea americana) and numerous native trees in the USA, Israel, and other countries. Currently, these pests are detected with quercivorol lure...

Monitoring wheat mitochondrial compositional and respiratory changes using Fourier transform mid-infrared spectroscopy in response to agrochemical treatments

USDA-ARS?s Scientific Manuscript database

Fungicides and plant growth regulators can impact plant growth outside of their effects on fungal pathogens. Although many of these chemicals are inhibitors of mitochondrial oxygen uptake, information remains limited as to whether they are able tomodify other mitochondrial constituents. Fourier tran...

Parasitism by Cuscuta pentagona attenuates host plant defenses against insect herbivores

Treesearch

Justin B. Runyon; Mark C. Mescher; Consuelo M. De Moraes

2008-01-01

Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (

Response of the honey bee (Apis mellifera L.) proteome to Israeli acute paralysis virus infection

USDA-ARS?s Scientific Manuscript database

Recent declines in honey bee populations worldwide have spurred significant research into the impact of pathogens on colony health. The role of the Israeli Acute Paralysis Virus (IAPV)on hive mortality has become of particular concern since being correlated with colony losses, although the pathogeni...

Natural killer cells as a therapeutic tool for infectious diseases – current status and future perspectives

PubMed Central

Schmidt, Stanislaw; Tramsen, Lars; Rais, Bushra; Ullrich, Evelyn; Lehrnbecher, Thomas

2018-01-01

Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells. To date, relatively little is known about the potential of adoptively transferring NK cells in immunocompromised patients with infectious complications, although the anti-cancer property of NK cells is already being investigated in the clinical setting. This review will focus on the antimicrobial properties of NK cells and the current standing and future perspectives of generating and using NK cells as immunotherapy in patients with infectious complications, an approach which is promising and might have an important clinical impact in the future. PMID:29755697

Nuclear processes associated with plant immunity and pathogen susceptibility

PubMed Central

Motion, Graham B.; Amaro, Tiago M.M.M.; Kulagina, Natalja

2015-01-01

Plants are sessile organisms that have evolved exquisite and sophisticated mechanisms to adapt to their biotic and abiotic environment. Plants deploy receptors and vast signalling networks to detect, transmit and respond to a given biotic threat by inducing properly dosed defence responses. Genetic analyses and, more recently, next-generation -omics approaches have allowed unprecedented insights into the mechanisms that drive immunity. Similarly, functional genomics and the emergence of pathogen genomes have allowed reciprocal studies on the mechanisms governing pathogen virulence and host susceptibility, collectively allowing more comprehensive views on the processes that govern disease and resistance. Among others, the identification of secreted pathogen molecules (effectors) that modify immunity-associated processes has changed the plant–microbe interactions conceptual landscape. Effectors are now considered both important factors facilitating disease and novel probes, suited to study immunity in plants. In this review, we will describe the various mechanisms and processes that take place in the nucleus and help regulate immune responses in plants. Based on the premise that any process required for immunity could be targeted by pathogen effectors, we highlight and describe a number of functional assays that should help determine effector functions and their impact on immune-related processes. The identification of new effector functions that modify nuclear processes will help dissect nuclear signalling further and assist us in our bid to bolster immunity in crop plants. PMID:25846755

Nuclear processes associated with plant immunity and pathogen susceptibility.

PubMed

Motion, Graham B; Amaro, Tiago M M M; Kulagina, Natalja; Huitema, Edgar

2015-07-01

Plants are sessile organisms that have evolved exquisite and sophisticated mechanisms to adapt to their biotic and abiotic environment. Plants deploy receptors and vast signalling networks to detect, transmit and respond to a given biotic threat by inducing properly dosed defence responses. Genetic analyses and, more recently, next-generation -omics approaches have allowed unprecedented insights into the mechanisms that drive immunity. Similarly, functional genomics and the emergence of pathogen genomes have allowed reciprocal studies on the mechanisms governing pathogen virulence and host susceptibility, collectively allowing more comprehensive views on the processes that govern disease and resistance. Among others, the identification of secreted pathogen molecules (effectors) that modify immunity-associated processes has changed the plant-microbe interactions conceptual landscape. Effectors are now considered both important factors facilitating disease and novel probes, suited to study immunity in plants. In this review, we will describe the various mechanisms and processes that take place in the nucleus and help regulate immune responses in plants. Based on the premise that any process required for immunity could be targeted by pathogen effectors, we highlight and describe a number of functional assays that should help determine effector functions and their impact on immune-related processes. The identification of new effector functions that modify nuclear processes will help dissect nuclear signalling further and assist us in our bid to bolster immunity in crop plants. © The Author 2015. Published by Oxford University Press.

Comparative analysis of the root transcriptomes of cultivated and wild rice varieties in response to Magnaporthe oryzae infection revealed both common and species-specific pathogen responses.

PubMed

Tian, Lei; Shi, Shaohua; Nasir, Fahad; Chang, Chunling; Li, Weiqiang; Tran, Lam-Son Phan; Tian, Chunjie

2018-04-20

Magnaporthe oryzae, the causal fungus of rice blast disease, negatively impacts global rice production. Wild rice (Oryza rufipogon), a relative of cultivated rice (O. sativa), possesses unique attributes that enable it to resist pathogen invasion. Although wild rice represents a major resource for disease resistance, relative to current cultivated rice varieties, no prior studies have compared the immune and transcriptional responses in the roots of wild and cultivated rice to M. oryzae. In this study, we showed that M. oryzae could act as a typical root-infecting pathogen in rice, in addition to its common infection of leaves, and wild rice roots were more resistant to M. oryzae than cultivated rice roots. Next, we compared the differential responses of wild and cultivated rice roots to M. oryzae using RNA-sequencing (RNA-seq) to unravel the molecular mechanisms underlying the enhanced resistance of the wild rice roots. Results indicated that both common and genotype-specific mechanisms exist in both wild and cultivated rice that are associated with resistance to M. oryzae. In wild rice, resistance mechanisms were associated with lipid metabolism, WRKY transcription factors, chitinase activities, jasmonic acid, ethylene, lignin, and phenylpropanoid and diterpenoid metabolism; while the pathogen responses in cultivated rice were mainly associated with phenylpropanoid, flavone and wax metabolism. Although modulations in primary metabolism and phenylpropanoid synthesis were common to both cultivated and wild rice, the modulation of secondary metabolism related to phenylpropanoid synthesis was associated with lignin synthesis in wild rice and flavone synthesis in cultivated rice. Interestingly, while the expression of fatty acid and starch metabolism-related genes was altered in both wild and cultivated rice in response to the pathogen, changes in lipid acid synthesis and lipid acid degradation were dominant in cultivated and wild rice, respectively. The response mechanisms to M. oryzae were more complex in wild rice than what was observed in cultivated rice. Therefore, this study may have practical implications for controlling M. oryzae in rice plantings and will provide useful information for incorporating and assessing disease resistance to M. oryzae in rice breeding programs.

Silencing of genes involved in Anaplasma marginale-tick interactions affects the pathogen developmental cycle in Dermacentor variabilis.

PubMed

Kocan, Katherine M; Zivkovic, Zorica; Blouin, Edmour F; Naranjo, Victoria; Almazán, Consuelo; Mitra, Ruchira; de la Fuente, José

2009-07-16

The cattle pathogen, Anaplasma marginale, undergoes a developmental cycle in ticks that begins in gut cells. Transmission to cattle occurs from salivary glands during a second tick feeding. At each site of development two forms of A. marginale (reticulated and dense) occur within a parasitophorous vacuole in the host cell cytoplasm. However, the role of tick genes in pathogen development is unknown. Four genes, found in previous studies to be differentially expressed in Dermacentor variabilis ticks in response to infection with A. marginale, were silenced by RNA interference (RNAi) to determine the effect of silencing on the A. marginale developmental cycle. These four genes encoded for putative glutathione S-transferase (GST), salivary selenoprotein M (SelM), H+ transporting lysosomal vacuolar proton pump (vATPase) and subolesin. The impact of gene knockdown on A. marginale tick infections, both after acquiring infection and after a second transmission feeding, was determined and studied by light microscopy. Silencing of these genes had a different impact on A. marginale development in different tick tissues by affecting infection levels, the densities of colonies containing reticulated or dense forms and tissue morphology. Salivary gland infections were not seen in any of the gene-silenced ticks, raising the question of whether these ticks were able to transmit the pathogen. The results of this RNAi and light microscopic analyses of tick tissues infected with A. marginale after the silencing of genes functionally important for pathogen development suggest a role for these molecules during pathogen life cycle in ticks.

Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.

PubMed

Salim, Taha; Sershen, Cheryl L; May, Elebeoba E

2016-01-01

Macrophage produced inducible nitric oxide synthase (iNOS) is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO) by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS), iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.

Very Virulent Infectious Bursal Disease Virus Produces More-Severe Disease and Lesions in Specific-Pathogen-Free (SPF) Leghorns Than in SPF Broiler Chickens.

PubMed

Sá e Silva, Mariana; Rissi, Daniel R; Swayne, David E

2016-03-01

Infectious bursal disease virus (IBDV) is an important pathogen of chickens causing negative economic impacts in poultry industries worldwide. IBDV has a variable range of virulence, with very virulent (vvIBDV) strains being responsible for the greatest losses from mortality and decreased performance. Previous vvIBDV studies using conventional broilers reported resistance to lethal effects and decreased performance as compared to specific-pathogen-free (SPF) layers, but the potential contribution of the conventional vs. SPF status to resistance has not been examined. In this study we compared differences in the acute pathologic effects of infection by the California rA strain of vvIBDV for SPF white leghorn egg-laying chickens and SPF white Plymouth Rock broiler chickens over a 7-day experimental period. Based on the clinical signs and mortality observed, as well as on the more-severe pathologic changes in lymphoid tissues and kidneys, white leghorns were shown to be more susceptible to the deleterious effects of vvIBDV infection than were white Plymouth Rocks. This study provides important information on the impact of chicken breed on susceptibility to vvIBDV and the absence of impact from conventional vs. SPF status on the outcome.

Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in Remote Tropical Settings

PubMed Central

Lubell, Yoel; Althaus, Thomas; Blacksell, Stuart D.; Paris, Daniel H.; Mayxay, Mayfong; Pan-Ngum, Wirichada; White, Lisa J.; Day, Nicholas P. J.; Newton, Paul N.

2016-01-01

Background Malaria accounts for a small fraction of febrile cases in increasingly large areas of the malaria endemic world. Point-of-care tests to improve the management of non-malarial fevers appropriate for primary care are few, consisting of either diagnostic tests for specific pathogens or testing for biomarkers of host response that indicate whether antibiotics might be required. The impact and cost-effectiveness of these approaches are relatively unexplored and methods to do so are not well-developed. Methods We model the ability of dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared with testing for elevated C-Reactive Protein (CRP), a biomarker of host-inflammation. Using data on causes of fever in rural Laos, we estimate the proportion of outpatients that would be correctly classified as requiring an antibiotic and the likely cost-effectiveness of the approaches. Results Use of either pathogen-specific test slightly increased the proportion of patients correctly classified as requiring antibiotics. CRP testing was consistently superior to the pathogen-specific tests, despite heterogeneity in causes of fever. All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively. Conclusions Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients. Testing for prevalent bacterial pathogens can be cost-effective, having the benefit of informing not only whether treatment is required, but also as to the most appropriate antibiotic; this advantage, however, varies widely in response to heterogeneity in causes of fever. Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections. PMID:27027303

Respiratory Viruses and Treatment Failure in Children With Asthma Exacerbation.

PubMed

Merckx, Joanna; Ducharme, Francine M; Martineau, Christine; Zemek, Roger; Gravel, Jocelyn; Chalut, Dominic; Poonai, Naveen; Quach, Caroline

2018-06-04

: media-1vid110.1542/5771275574001PEDS-VA_2017-4105 Video Abstract OBJECTIVES: Respiratory pathogens commonly trigger pediatric asthma exacerbations, but their impact on severity and treatment response remains unclear. We performed a secondary analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study, a prospective cohort study of children (aged 1-17 years) presenting to the emergency department with moderate or severe exacerbations. Nasopharyngeal specimens were analyzed by RT-PCR for 27 respiratory pathogens. We investigated the association between pathogens and both exacerbation severity (assessed with the Pediatric Respiratory Assessment Measure) and treatment failure (hospital admission, emergency department stay >8 hours, or relapse) of a standardized severity-specific treatment. Logistic multivariate regressions were used to estimate average marginal effects (absolute risks and risk differences [RD]). Of 958 participants, 61.7% were positive for ≥1 pathogen (rhinovirus was the most prevalent [29.4%]) and 16.9% experienced treatment failure. The presence of any pathogen was not associated with higher baseline severity but with a higher risk of treatment failure (20.7% vs 12.5%; RD = 8.2% [95% confidence interval: 3.3% to 13.1%]) compared to the absence of a pathogen. Nonrhinovirus pathogens were associated with an increased absolute risk (RD) of treatment failure by 13.1% (95% confidence interval: 6.4% to 19.8%), specifically, by 8.8% for respiratory syncytial virus, 24.9% for influenza, and 34.1% for parainfluenza. Although respiratory pathogens were not associated with higher severity on presentation, they were associated with increased treatment failure risk, particularly in the presence of respiratory syncytial virus, influenza, and parainfluenza. This supports influenza prevention in asthmatic children, consideration of pathogen identification on presentation, and exploration of treatment intensification for infected patients at higher risk of treatment failure. Copyright © 2018 by the American Academy of Pediatrics.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.

PubMed

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M; Casadevall, Arturo; Flynn, JoAnne

2014-12-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection

PubMed Central

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M.; Casadevall, Arturo; Flynn, JoAnne

2014-01-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. PMID:25458990

Thermal Stress Triggers Broad Pocillopora damicornis Transcriptomic Remodeling, while Vibrio coralliilyticus Infection Induces a More Targeted Immuno-Suppression Response

PubMed Central

Vidal-Dupiol, Jeremie; Dheilly, Nolwenn M.; Rondon, Rodolfo; Grunau, Christoph; Cosseau, Céline; Smith, Kristina M.; Freitag, Michael; Adjeroud, Mehdi; Mitta, Guillaume

2014-01-01

Global change and its associated temperature increase has directly or indirectly changed the distributions of hosts and pathogens, and has affected host immunity, pathogen virulence and growth rates. This has resulted in increased disease in natural plant and animal populations worldwide, including scleractinian corals. While the effects of temperature increase on immunity and pathogen virulence have been clearly identified, their interaction, synergy and relative weight during pathogenesis remain poorly documented. We investigated these phenomena in the interaction between the coral Pocillopora damicornis and the bacterium Vibrio coralliilyticus, for which the infection process is temperature-dependent. We developed an experimental model that enabled unraveling the effects of thermal stress, and virulence vs. non-virulence of the bacterium. The physiological impacts of various treatments were quantified at the transcriptome level using a combination of RNA sequencing and targeted approaches. The results showed that thermal stress triggered a general weakening of the coral, making it more prone to infection, non-virulent bacterium induced an ‘efficient’ immune response, whereas virulent bacterium caused immuno-suppression in its host. PMID:25259845

Detection Methodologies for Pathogen and Toxins: A Review.

PubMed

Alahi, Md Eshrat E; Mukhopadhyay, Subhas Chandra

2017-08-16

Pathogen and toxin-contaminated foods and beverages are a major source of illnesses, even death, and have a significant economic impact worldwide. Human health is always under a potential threat, including from biological warfare, due to these dangerous pathogens. The agricultural and food production chain consists of many steps such as harvesting, handling, processing, packaging, storage, distribution, preparation, and consumption. Each step is susceptible to threats of environmental contamination or failure to safeguard the processes. The production process can be controlled in the food and agricultural sector, where smart sensors can play a major role, ensuring greater food quality and safety by low cost, fast, reliable, and profitable methods of detection. Techniques for the detection of pathogens and toxins may vary in cost, size, and specificity, speed of response, sensitivity, and precision. Smart sensors can detect, analyse and quantify at molecular levels contents of different biological origin and ensure quality of foods against spiking with pesticides, fertilizers, dioxin, modified organisms, anti-nutrients, allergens, drugs and so on. This paper reviews different methodologies to detect pathogens and toxins in foods and beverages.

Virulence and Immunomodulatory Roles of Bacterial Outer Membrane Vesicles

PubMed Central

Ellis, Terri N.; Kuehn, Meta J.

2010-01-01

Summary: Outer membrane (OM) vesicles are ubiquitously produced by Gram-negative bacteria during all stages of bacterial growth. OM vesicles are naturally secreted by both pathogenic and nonpathogenic bacteria. Strong experimental evidence exists to categorize OM vesicle production as a type of Gram-negative bacterial virulence factor. A growing body of data demonstrates an association of active virulence factors and toxins with vesicles, suggesting that they play a role in pathogenesis. One of the most popular and best-studied pathogenic functions for membrane vesicles is to serve as natural vehicles for the intercellular transport of virulence factors and other materials directly into host cells. The production of OM vesicles has been identified as an independent bacterial stress response pathway that is activated when bacteria encounter environmental stress, such as what might be experienced during the colonization of host tissues. Their detection in infected human tissues reinforces this theory. Various other virulence factors are also associated with OM vesicles, including adhesins and degradative enzymes. As a result, OM vesicles are heavily laden with pathogen-associated molecular patterns (PAMPs), virulence factors, and other OM components that can impact the course of infection by having toxigenic effects or by the activation of the innate immune response. However, infected hosts can also benefit from OM vesicle production by stimulating their ability to mount an effective defense. Vesicles display antigens and can elicit potent inflammatory and immune responses. In sum, OM vesicles are likely to play a significant role in the virulence of Gram-negative bacterial pathogens. PMID:20197500

Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae

PubMed Central

Heroven, Ann Kathrin; Dersch, Petra

2014-01-01

Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets. PMID:25368845

Quantitative analysis of contents and volatile emissions from a-copaene and quercivorol lures, and longevity for attraction of Euwallacea nr. fornicatus in Florida

USDA-ARS?s Scientific Manuscript database

Ambrosia beetles in the cryptic species complex Euwallacea nr. fornicatus vector a fungal pathogen responsible for Fusarium dieback, a disease that impacts avocado (Persea americana) and numerous native trees in the USA (California, Florida), Israel, and other countries. Currently, these pests are d...

Using multi-trait and random regression models to identify genetic variation in tolerance of pigs to Porcine Reproductive and Respiratory Syndrome virus

USDA-ARS?s Scientific Manuscript database

Background A host can adopt two response strategies to infection: resistance (reduce pathogen load) and tolerance (minimize impact of infection on performance). Both strategies may be under genetic control and could thus be targeted for genetic improvement. Although there is evidence in support of a...

RNA-Seq analysis reveals insight into enhanced rice Xa7-mediated bacterial blight resistance at high temperature.

PubMed

Cohen, Stephen P; Liu, Hongxia; Argueso, Cristiana T; Pereira, Andy; Vera Cruz, Casiana; Verdier, Valerie; Leach, Jan E

2017-01-01

Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61) containing Xa7, a bacterial blight disease resistance (R) gene, that were infected with Xanthomonas oryzae, the bacterial blight pathogen of rice, during high temperature stress. Xa7-mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7-mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7-mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis-regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant hormone abscisic acid is an important node for cross-talk between plant transcriptional response pathways to high temperature stress and pathogen attack. Genes in this pathway represent an important focus for future study to determine how plants evolved to deal with simultaneous abiotic and biotic stresses.

RNA-Seq analysis reveals insight into enhanced rice Xa7-mediated bacterial blight resistance at high temperature

PubMed Central

Argueso, Cristiana T.; Pereira, Andy; Vera Cruz, Casiana; Verdier, Valerie

2017-01-01

Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61) containing Xa7, a bacterial blight disease resistance (R) gene, that were infected with Xanthomonas oryzae, the bacterial blight pathogen of rice, during high temperature stress. Xa7-mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7-mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7-mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis-regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant hormone abscisic acid is an important node for cross-talk between plant transcriptional response pathways to high temperature stress and pathogen attack. Genes in this pathway represent an important focus for future study to determine how plants evolved to deal with simultaneous abiotic and biotic stresses. PMID:29107972

Pathogen dynamics during invasion and establishment of white-nose syndrome explain mechanisms of host persistence.

PubMed

Frick, Winifred F; Cheng, Tina L; Langwig, Kate E; Hoyt, Joseph R; Janicki, Amanda F; Parise, Katy L; Foster, Jeffrey T; Kilpatrick, A Marm

2017-03-01

Disease dynamics during pathogen invasion and establishment determine the impacts of disease on host populations and determine the mechanisms of host persistence. Temporal progression of prevalence and infection intensity illustrate whether tolerance, resistance, reduced transmission, or demographic compensation allow initially declining populations to persist. We measured infection dynamics of the fungal pathogen Pseudogymnoascus destructans that causes white-nose syndrome in bats by estimating pathogen prevalence and load in seven bat species at 167 hibernacula over a decade as the pathogen invaded, became established, and some host populations stabilized. Fungal loads increased rapidly and prevalence rose to nearly 100% at most sites within 2 yr of invasion in six of seven species. Prevalence and loads did not decline over time despite huge reductions in colony sizes, likely due to an extensive environmental reservoir. However, there was substantial variation in fungal load among sites with persisting colonies, suggesting that both tolerance and resistance developed at different sites in the same species. In contrast, one species disappeared from hibernacula within 3 yr of pathogen invasion. Variable host responses to pathogen invasion require different management strategies to prevent disease-induced extinction and to facilitate evolution of tolerance or resistance in persisting populations. © 2016 by the Ecological Society of America.

Exogenous Polyunsaturated Fatty Acids Impact Membrane Remodeling and Affect Virulence Phenotypes among Pathogenic Vibrio Species

PubMed Central

Moravec, Anna R.; Siv, Andrew W.; Hobby, Chelsea R.; Lindsay, Emily N.; Norbash, Layla V.; Shults, Daniel J.; Symes, Steven J. K.

2017-01-01

ABSTRACT The pathogenic Vibrio species (V. cholerae, V. parahaemolyticus, and V. vulnificus) represent a constant threat to human health, causing foodborne and skin wound infections as a result of ingestion of or exposure to contaminated water and seafood. Recent studies have highlighted Vibrio's ability to acquire fatty acids from environmental sources and assimilate them into cell membranes. The possession and conservation of such machinery provokes consideration of fatty acids as important factors in the pathogenic lifestyle of Vibrio species. The findings here link exogenous fatty acid exposure to changes in bacterial membrane phospholipid structure, permeability, phenotypes associated with virulence, and consequent stress responses that may impact survival and persistence of pathogenic Vibrio species. Polyunsaturated fatty acids (PUFAs) (ranging in carbon length and unsaturation) supplied in growth medium were assimilated into bacterial phospholipids, as determined by thin-layer chromatography and liquid chromatography-mass spectrometry. The incorporation of fatty acids variably affected membrane permeability, as judged by uptake of the hydrophobic compound crystal violet. For each species, certain fatty acids were identified as affecting resistance to antimicrobial peptide treatment. Significant fluctuations were observed with regard to both motility and biofilm formation following growth in the presence of individual PUFAs. Our results illustrate the important and complex roles of exogenous fatty acids in the membrane physiology and virulence of a bacterial genus that inhabits aquatic and host environments containing an abundance of diverse fatty acids. IMPORTANCE Bacterial responses to fatty acids include, but are not limited to, degradation for metabolic gain, modification of membrane lipids, alteration of protein function, and regulation of gene expression. Vibrio species exhibit significant diversity with regard to the machinery known to participate in the uptake and incorporation of fatty acids into their membranes. Both aquatic and host niches occupied by Vibrio are rife with various free fatty acids and fatty acid-containing lipids. The roles of fatty acids in the environmental survival and pathogenesis of bacteria have begun to emerge and are expected to expand significantly. The current study demonstrates the responsiveness of V. cholerae, V. parahaemolyticus, and V. vulnificus to exogenous PUFAs. In addition to phospholipid remodeling, PUFA assimilation impacts membrane permeability, motility, biofilm formation, and resistance to polymyxin B. PMID:28864654

Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen

PubMed Central

Barry, Kevin C; Ingolia, Nicholas T; Vance, Russell E

2017-01-01

The inducible innate immune response to infection requires a concerted process of gene expression that is regulated at multiple levels. Most global analyses of the innate immune response have focused on transcription induced by defined immunostimulatory ligands, such as lipopolysaccharide. However, the response to pathogens involves additional complexity, as pathogens interfere with virtually every step of gene expression. How cells respond to pathogen-mediated disruption of gene expression to nevertheless initiate protective responses remains unclear. We previously discovered that a pathogen-mediated blockade of host protein synthesis provokes the production of specific pro-inflammatory cytokines. It remains unclear how these cytokines are produced despite the global pathogen-induced block of translation. We addressed this question by using parallel RNAseq and ribosome profiling to characterize the response of macrophages to infection with the intracellular bacterial pathogen Legionella pneumophila. Our results reveal that mRNA superinduction is required for the inducible immune response to a bacterial pathogen. DOI: http://dx.doi.org/10.7554/eLife.22707.001 PMID:28383283

Respiratory Pathogens Adopt a Chronic Lifestyle in Response to Bile

PubMed Central

Reen, F. Jerry; Woods, David F.; Mooij, Marlies J.; Adams, Claire; O'Gara, Fergal

2012-01-01

Chronic respiratory infections are a major cause of morbidity and mortality, most particularly in Cystic Fibrosis (CF) patients. The recent finding that gastro-esophageal reflux (GER) frequently occurs in CF patients led us to investigate the impact of bile on the behaviour of Pseudomonas aeruginosa and other CF-associated respiratory pathogens. Bile increased biofilm formation, Type Six Secretion, and quorum sensing in P. aeruginosa, all of which are associated with the switch from acute to persistent infection. Furthermore, bile negatively influenced Type Three Secretion and swarming motility in P. aeruginosa, phenotypes associated with acute infection. Bile also modulated biofilm formation in a range of other CF-associated respiratory pathogens, including Burkholderia cepacia and Staphylococcus aureus. Therefore, our results suggest that GER-derived bile may be a host determinant contributing to chronic respiratory infection. PMID:23049911

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

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

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhancedmore » approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.« less

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development.

PubMed

Adams, L Garry; Khare, Sangeeta; Lawhon, Sara D; Rossetti, Carlos A; Lewin, Harris A; Lipton, Mary S; Turse, Joshua E; Wylie, Dennis C; Bai, Yu; Drake, Kenneth L

2011-09-22

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host-pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic ΔsipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host-pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host-pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

PubMed

Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael; Moriarty, Tara J

2016-01-01

Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

Genetic erosion in wild populations makes resistance to a pathogen more costly.

PubMed

Luquet, Emilien; Garner, Trenton W J; Léna, Jean-Paul; Bruel, Christophe; Joly, Pierre; Lengagne, Thierry; Grolet, Odile; Plénet, Sandrine

2012-06-01

Populations that have suffered from genetic erosion are expected to exhibit reduced average trait values or decreased variation in adaptive traits when experiencing periodic or emergent stressors such as infectious disease. Genetic erosion may consequentially modify the ability of a potential host population to cope with infectious disease emergence. We experimentally investigate this relationship between genetic variability and host response to exposure to an infectious agent both in terms of susceptibility to infection and indirect parasite-mediated responses that also impact fitness. We hypothesized that the deleterious consequences of exposure to the pathogen (Batrachochytrium dendrobatidis) would be more severe for tadpoles descended from European treefrog (Hyla arborea) populations lacking genetic variability. Although all exposed tadpoles lacked detectable infection, we detected this relationship for some indirect host responses, predominantly in genetically depleted animals, as well as an interaction between genetic variability and pathogen dose on life span during the postmetamorphic period. Lack of infection and a decreased mass and postmetamorphic life span in low genetic diversity tadpoles lead us to conclude that genetic erosion, while not affecting the ability to mount effective resistance strategies, also erodes the capacity to invest in resistance, increased tadpole growth rate, and metamorphosis relatively simultaneously. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

Humanized TLR4/MD-2 mice reveal LPS recognition differentially impacts susceptibility to Yersinia pestis and Salmonella enterica.

PubMed

Hajjar, Adeline M; Ernst, Robert K; Fortuno, Edgardo S; Brasfield, Alicia S; Yam, Cathy S; Newlon, Lindsay A; Kollmann, Tobias R; Miller, Samuel I; Wilson, Christopher B

2012-01-01

Although lipopolysaccharide (LPS) stimulation through the Toll-like receptor (TLR)-4/MD-2 receptor complex activates host defense against Gram-negative bacterial pathogens, how species-specific differences in LPS recognition impact host defense remains undefined. Herein, we establish how temperature dependent shifts in the lipid A of Yersinia pestis LPS that differentially impact recognition by mouse versus human TLR4/MD-2 dictate infection susceptibility. When grown at 37°C, Y. pestis LPS is hypo-acylated and less stimulatory to human compared with murine TLR4/MD-2. By contrast, when grown at reduced temperatures, Y. pestis LPS is more acylated, and stimulates cells equally via human and mouse TLR4/MD-2. To investigate how these temperature dependent shifts in LPS impact infection susceptibility, transgenic mice expressing human rather than mouse TLR4/MD-2 were generated. We found the increased susceptibility to Y. pestis for "humanized" TLR4/MD-2 mice directly paralleled blunted inflammatory cytokine production in response to stimulation with purified LPS. By contrast, for other Gram-negative pathogens with highly acylated lipid A including Salmonella enterica or Escherichia coli, infection susceptibility and the response after stimulation with LPS were indistinguishable between mice expressing human or mouse TLR4/MD-2. Thus, Y. pestis exploits temperature-dependent shifts in LPS acylation to selectively evade recognition by human TLR4/MD-2 uncovered with "humanized" TLR4/MD-2 transgenic mice.

Early Salmonella Typhimurium infection in pigs disrupts Microbiome composition and functionality principally at the ileum mucosa.

PubMed

Argüello, Héctor; Estellé, Jordi; Zaldívar-López, Sara; Jiménez-Marín, Ángeles; Carvajal, Ana; López-Bascón, Mª Asunción; Crispie, Fiona; O'Sullivan, Orla; Cotter, Paul D; Priego-Capote, Feliciano; Morera, Luis; Garrido, Juan J

2018-05-17

Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen's ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection.

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

PubMed

Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive disease in the population, especially among the elderly and others most susceptible to pneumococcal disease. However, these effects may also be beneficial, for example the large reductions in all-cause mortality noted following measles vaccines. Here we discuss evidence for these novel vaccine effects and suggest that vaccine monitoring and evaluation programs should consider generalized herd effects to appreciate the full impacts of vaccines, beneficial or detrimental, across species and scales that are inevitably hiding in plain sight, affecting human health and disease. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

PubMed Central

López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C.; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

2016-01-01

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen multiplication and promote survival, facilitating pathogen transmission. PMID:27027307

The role of nitric oxide in the interaction of Arabidopsis thaliana with the biotrophic fungi, Golovinomyces orontii and Erysiphe pisi.

PubMed

Schlicht, Markus; Kombrink, Erich

2013-01-01

Powdery mildews are a diverse group of pathogenic fungi that can infect a large number of plant species, including many economically important crops. However, basic and applied research on these devastating diseases has been hampered by the obligate biotrophic lifestyle of the pathogens, which require living host cells for growth and reproduction, and lacking genetic and molecular tools for important host plants. The establishment of Arabidopsis thaliana as a host of different powdery mildew species allowed pursuing new strategies to study the molecular mechanisms governing these complex plant-pathogen interactions. Nitric oxide (NO) has emerged as an important signaling molecule in plants, which is produced upon infection and involved in activation of plant immune responses. However, the source and pathway of NO production and its precise function in the regulatory network of reactions leading to resistance is still unknown. We studied the response of Arabidopsis thaliana to infection with the adapted powdery mildew, Golovinomyces orontii (compatible interaction) and the non-adapted, Erysiphe pisi (incompatible interaction). We observed that NO accumulated rapidly and transiently at infection sites and we established a correlation between the resistance phenotype and the amount and timing of NO production. Arabidopsis mutants with defective immune response accumulated lower NO levels compared to wild type. Conversely, increased NO levels, generated by treatment with chemicals or expression of a NO-synthesizing enzyme, resulted in enhanced resistance, but only sustained NO production prevented excessive leaf colonization by the fungus, which was not achieved by a short NO burst although this reduced the initial penetration success. By contrast, lowered NO levels did not impair the ultimate resistance phenotype. Although our results suggest a function of NO in mediating plant immune responses, a direct impact on pathogen growth and development cannot be excluded.

Dose-response relationships for environmentally mediated infectious disease transmission models

PubMed Central

Eisenberg, Joseph N. S.

2017-01-01

Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose–response relationship. Much of the work characterizing the functional forms of dose–response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose–response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i) middle- and high-dose data do not constrain the low-dose response, and different dose–response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii) the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii) low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv) identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain. PMID:28388665

Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity

PubMed Central

Smith, Judith A.

2018-01-01

Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation. The UPR influences cytokine production on multiple levels, from stimulation of pattern recognition receptors, to modulation of inflammatory signaling pathways, and the regulation of cytokine transcription factors. This review will focus on the mechanisms underlying cytokine regulation by the UPR, and the repercussions of this relationship for infection and autoimmune/autoinflammatory diseases. Interrogation of viral and bacterial infections has revealed increasing numbers of examples where pathogens induce or modulate the UPR and implicated UPR-modulated cytokines in host response. The flip side of this coin, the UPR/ER stress responses have been increasingly recognized in a variety of autoimmune and inflammatory diseases. Examples include monogenic disorders of ER function, diseases linked to misfolding protein (HLA-B27 and spondyloarthritis), diseases directly implicating UPR and autophagy genes (inflammatory bowel disease), and autoimmune diseases targeting highly secretory cells (e.g., diabetes). Given the burgeoning interest in pharmacologically targeting the UPR, greater discernment is needed regarding how the UPR regulates cytokine production during specific infections and autoimmune processes, and the relative place of this interaction in pathogenesis. PMID:29556237

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.

Impact of Combined Abiotic and Biotic Stresses on Plant Growth and Avenues for Crop Improvement by Exploiting Physio-morphological Traits

PubMed Central

Pandey, Prachi; Irulappan, Vadivelmurugan; Bagavathiannan, Muthukumar V.; Senthil-Kumar, Muthappa

2017-01-01

Global warming leads to the concurrence of a number of abiotic and biotic stresses, thus affecting agricultural productivity. Occurrence of abiotic stresses can alter plant–pest interactions by enhancing host plant susceptibility to pathogenic organisms, insects, and by reducing competitive ability with weeds. On the contrary, some pests may alter plant response to abiotic stress factors. Therefore, systematic studies are pivotal to understand the effect of concurrent abiotic and biotic stress conditions on crop productivity. However, to date, a collective database on the occurrence of various stress combinations in agriculturally prominent areas is not available. This review attempts to assemble published information on this topic, with a particular focus on the impact of combined drought and pathogen stresses on crop productivity. In doing so, this review highlights some agriculturally important morpho-physiological traits that can be utilized to identify genotypes with combined stress tolerance. In addition, this review outlines potential role of recent genomic tools in deciphering combined stress tolerance in plants. This review will, therefore, be helpful for agronomists and field pathologists in assessing the impact of the interactions between drought and plant-pathogens on crop performance. Further, the review will be helpful for physiologists and molecular biologists to design agronomically relevant strategies for the development of broad spectrum stress tolerant crops. PMID:28458674

Differential immune response of mallard duck peripheral blood mononuclear cells to two highly pathogenic avian influenza H5N1 viruses with distinct pathogenicity in mallard ducks.

PubMed

Cui, Zhu; Hu, Jiao; He, Liang; Li, Qunhui; Gu, Min; Wang, Xiaoquan; Hu, Shunlin; Liu, Huimou; Liu, Wenbo; Liu, Xiaowen; Liu, Xiufan

2014-02-01

CK10 and GS10 are two H5N1 highly pathogenic influenza viruses of similar genetic background but differ in their pathogenicity in mallard ducks. CK10 is highly pathogenic whereas GS10 is low pathogenic. In this study, strong inflammatory response in terms of the expression level of several cytokines was observed in mallard duck peripheral blood mononuclear cells (PBMC) infected with CK10 while mild response was triggered in those by GS10 infection. Two remarkable and intense peaks of immune response were induced by CK10 infection within 24 hours (at 8 and 24 hours post infection, respectively) without reducing the virus replication. Our observations indicated that sustained and intense innate immune responses may be central to the high pathogenicity caused by CK10 in ducks.

Chitosan in Plant Protection

PubMed Central

El Hadrami, Abdelbasset; Adam, Lorne R.; El Hadrami, Ismail; Daayf, Fouad

2010-01-01

Chitin and chitosan are naturally-occurring compounds that have potential in agriculture with regard to controlling plant diseases. These molecules were shown to display toxicity and inhibit fungal growth and development. They were reported to be active against viruses, bacteria and other pests. Fragments from chitin and chitosan are known to have eliciting activities leading to a variety of defense responses in host plants in response to microbial infections, including the accumulation of phytoalexins, pathogen-related (PR) proteins and proteinase inhibitors, lignin synthesis, and callose formation. Based on these and other proprieties that help strengthen host plant defenses, interest has been growing in using them in agricultural systems to reduce the negative impact of diseases on yield and quality of crops. This review recapitulates the properties and uses of chitin, chitosan, and their derivatives, and will focus on their applications and mechanisms of action during plant-pathogen interactions. PMID:20479963

Agricultural pathogen decontamination technology-reducing the threat of infectious agent spread.

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

Betty, Rita G.; Bieker, Jill Marie; Tucker, Mark David

Outbreaks of infectious agricultural diseases, whether natural occurring or introduced intentionally, could have catastrophic impacts on the U.S. economy. Examples of such agricultural pathogens include foot and mouth disease (FMD), avian influenza (AI), citrus canker, wheat and soy rust, etc. Current approaches to mitigate the spread of agricultural pathogens include quarantine, development of vaccines for animal diseases, and development of pathogen resistant crop strains in the case of plant diseases. None of these approaches is rapid, and none address the potential persistence of the pathogen in the environment, which could lead to further spread of the agent and damage aftermore » quarantine is lifted. Pathogen spread in agricultural environments commonly occurs via transfer on agricultural equipment (transportation trailers, tractors, trucks, combines, etc.), having components made from a broad range of materials (galvanized and painted steel, rubber tires, glass and Plexiglas shields, etc), and under conditions of heavy organic load (mud, soil, feces, litter, etc). A key element of stemming the spread of an outbreak is to ensure complete inactivation of the pathogens in the agricultural environment and on the equipment used in those environments. Through the combination of enhanced agricultural pathogen decontamination chemistry and a validated inactivation verification methodology, important technologies for incorporation as components of a robust response capability will be enabled. Because of the potentially devastating economic impact that could result from the spread of infectious agricultural diseases, the proposed capability components will promote critical infrastructure protection and greater border and food supply security. We investigated and developed agricultural pathogen decontamination technologies to reduce the threat of infectious-agent spread, and thus enhance agricultural biosecurity. Specifically, enhanced detergency versions of the patented Sandia decontamination chemistry were developed and tested against a few surrogate pathogens under conditions of relatively heavy organic load. Tests were conducted on surfaces commonly found in agricultural environments. Wide spectrum decontamination efficacy, low corrosivity, and biodegradability issues were addressed in developing an enhanced detergency formulation. A method for rapid assessment of loss of pathogenic activity (inactivation) was also assessed. This enhanced technology will enable rapid assessment of contamination following an intentional event, and will also be extremely useful in routine assessment of agricultural environments. The primary effort during the second year was progress towards a demonstration of both decontamination and viral inactivation technologies of Foot and Mouth virus (FMDv) using the modified SNL chemistry developed through this project. Lab studies using a surrogate virus (bovine enterovirus) were conducted using DF200, modified DF200 chemistry, and decontaminants currently recommended for use in heavily loaded organic, agricultural environments (VirkonS, 10% bleach, sodium hydroxide and citric acid). Tests using actual FMD virus will be performed at the Department of Homeland Security's Plum Island facilities in the fall of 2005. Success and the insight gained from this project will lead to enhanced response capability, which will benefit agencies such as USDA, DHS, DOD, and the agricultural industry.« less

Inducible defense against pathogens and parasites: optimal choice among multiple options.

PubMed

Shudo, E; Iwasa, Y

2001-03-21

Defense against pathogen, parasites and herbivores is often enhanced after their invasion into the host's body. Sometimes different options are adopted depending on the identity and the quantity of the pathogen, exemplified by the switch between Th1 and Th2 systems in mammalian immunity. In this paper, we study the optimal defense of the host when two alternative responses are available, which differ in the effectiveness of suppressing the growth of pathogen (parasite, or herbivore), the damage to the host caused by the defense response, and the magnitude of time delay before the defense response becomes fully effective. The optimal defense is the one that minimizes the sum of the damages caused by the pathogen and the cost due to defense activities. The damage by pathogens increases in proportion to the time integral of the pathogen abundance, and the cost is proportional to the defense activity. We can prove that a single globally optimal combination of defense options always exists and there is no other local optimum. Depending on the parameters, the optimal is to adopt only the early response, only the late response, or both responses. The defense response with a shorter time delay is more heavily used when the pathogen grows fast, the initial pathogen abundance is large, and the difference in time delay is long. We also study the host's optimal choice between constitutive and inducible defenses. In the constitutive defense, the response to pathogen attack works without delay, but it causes the cost even when the pathogen attack does not occur. We discuss mammalian immunity and the plant chemical defense from the model's viewpoint. Copyright 2001 Academic Press.

Host and tissue variations overshadow the response of boreal moss-associated fungal communities to increased nitrogen load.

PubMed

Davey, Marie L; Skogen, Marte J; Heegaard, Einar; Halvorsen, Rune; Kauserud, Håvard; Ohlson, Mikael

2017-01-01

Human activity has more than doubled the amount of nitrogen entering the global nitrogen cycle, and the boreal forest biome is a nitrogen-limited ecosystem sensitive to nitrogen load perturbation. Although bryophyte-associated microbes contribute significantly to boreal forest ecosystem function, particularly in carbon and nitrogen cycling, little is known about their responses to anthropogenic global change. Amplicon pyrosequencing of the ITS2 region of rDNA was used to investigate how fungal communities associated with three bryophyte species responded to increased nitrogen loads in a long-term fertilization experiment in a boreal Picea abies forest in southern Norway. Overall, OTU richness, community composition and the relative abundance of specific ecological guilds were primarily influenced by host species identity and tissue type. Although not the primary factor affecting fungal communities, nitrogen addition did impact the abundance of specific guilds of fungi and the resulting overall community composition. Increased nitrogen loads decreased ectomycorrhizal abundance, with Amphinema, Cortinarius, Russula and Tylospora OTUs responding negatively to fertilization. Pathogen abundance increased with fertilization, particularly in the moss pathogen Eocronartium. Saprophytic fungi were both positively and negatively impacted by the nitrogen addition, indicating a complex community level response. The overshadowing of the effects of increased nitrogen loads by variation related to host and tissue type highlights the complexity of bryophyte-associated microbial communities and the intricate nature of their responses to anthropogenic global change. © 2016 John Wiley & Sons Ltd.

What is the risk for exposure to vector-borne pathogens in United States national parks?

PubMed

Eisen, Lars; Wong, David; Shelus, Victoria; Eisen, Rebecca J

2013-03-01

United States national parks attract > 275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. We assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal National Park Service documents and organismal databases. We conclude that, because of lack of systematic surveillance for vector-borne pathogens in national parks, the risk of pathogen exposure for staff and visitors is unclear. Existing data for vectors within national parks were not based on systematic collections and rarely include evaluation for pathogen infection. Extrapolation of human-based surveillance data from neighboring communities likely provides inaccurate estimates for national parks because landscape differences impact transmission of vector-borne pathogens and human-vector contact rates likely differ inside versus outside the parks because of differences in activities or behaviors. Vector-based pathogen surveillance holds promise to define when and where within national parks the risk of exposure to infected vectors is elevated. A pilot effort, including 5-10 strategic national parks, would greatly improve our understanding of the scope and magnitude of vector-borne pathogen transmission in these high-use public settings. Such efforts also will support messaging to promote personal protection measures and inform park visitors and staff of their responsibility for personal protection, which the National Park Service preservation mission dictates as the core strategy to reduce exposure to vector-borne pathogens in national parks.

Rainfall and temperatures changes have confounding impacts on Phytophthora cinnamomi occurrence risk in the southwestern USA under climate change scenarios.

PubMed

Thompson, Sally E; Levin, Simon; Rodriguez-Iturbe, Ignacio

2014-04-01

Global change will simultaneously impact many aspects of climate, with the potential to exacerbate the risks posed by plant pathogens to agriculture and the natural environment; yet, most studies that explore climate impacts on plant pathogen ranges consider individual climatic factors separately. In this study, we adopt a stochastic modeling approach to address multiple pathways by which climate can constrain the range of the generalist plant pathogen Phytophthora cinnamomi (Pc): through changing winter soil temperatures affecting pathogen survival; spring soil temperatures and thus pathogen metabolic rates; and changing spring soil moisture conditions and thus pathogen growth rates through host root systems. We apply this model to the southwestern USA for contemporary and plausible future climate scenarios and evaluate the changes in the potential range of Pc. The results indicate that the plausible range of this pathogen in the southwestern USA extends over approximately 200,000 km(2) under contemporary conditions. While warming temperatures as projected by the IPCC A2 and B1 emissions scenarios greatly expand the range over which the pathogen can survive winter, projected reductions in spring rainfall reduce its feasible habitat, leading to spatially complex patterns of changing risk. The study demonstrates that temperature and rainfall changes associated with possible climate futures in the southwestern USA have confounding impacts on the range of Pc, suggesting that projections of future pathogen dynamics and ranges should account for multiple pathways of climate-pathogen interaction. © 2014 John Wiley & Sons Ltd.

Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes.

PubMed

Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg; Hartmann, Susanne

2016-05-01

Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. Copyright © 2016 Maaz et al.

Chlamydia Infection Across Host Species Boundaries Promotes Distinct Sets of Transcribed Anti-Apoptotic Factors

PubMed Central

Messinger, Joshua E.; Nelton, Emmalin; Feeney, Colleen; Gondek, David C.

2015-01-01

Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis) and respiratory associated disease (C. pneumoniae). The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the “arms race” of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs) elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases. PMID:26779446

Transcriptome profiling of soybean (Glycine max) roots challenged with pathogenic and non-pathogenic isolates of Fusarium oxysporum.

PubMed

Lanubile, Alessandra; Muppirala, Usha K; Severin, Andrew J; Marocco, Adriano; Munkvold, Gary P

2015-12-21

Fusarium oxysporum is one of the most common fungal pathogens causing soybean root rot and seedling blight in U.S.A. In a recent study, significant variation in aggressiveness was observed among isolates of F. oxysporum collected from roots in Iowa, ranging from highly pathogenic to weakly or non-pathogenic isolates. We used RNA-seq analysis to investigate the molecular aspects of the interactions of a partially resistant soybean genotype with non-pathogenic/pathogenic isolates of F. oxysporum at 72 and 96 h post inoculation (hpi). Markedly different gene expression profiles were observed in response to the two isolates. A peak of highly differentially expressed genes (HDEGs) was triggered at 72 hpi in soybean roots and the number of HDEGs was about eight times higher in response to the pathogenic isolate compared to the non-pathogenic one (1,659 vs. 203 HDEGs, respectively). Furthermore, the magnitude of induction was much greater in response to the pathogenic isolate. This response included a stronger activation of defense-related genes, transcription factors, and genes involved in ethylene biosynthesis, secondary and sugar metabolism. The obtained data provide an important insight into the transcriptional responses of soybean-F. oxysporum interactions and illustrate the more drastic changes in the host transcriptome in response to the pathogenic isolate. These results may be useful in the developing new methods of broadening resistance of soybean to F. oxysporum, including the over-expression of key soybean genes.

De novo genome assembly of the soil-borne fungus and tomato pathogen Pyrenochaeta lycopersici

PubMed Central

2014-01-01

Background Pyrenochaeta lycopersici is a soil-dwelling ascomycete pathogen that causes corky root rot disease in tomato (Solanum lycopersicum) and other Solanaceous crops, reducing fruit yields by up to 75%. Fungal pathogens that infect roots receive less attention than those infecting the aerial parts of crops despite their significant impact on plant growth and fruit production. Results We assembled a 54.9Mb P. lycopersici draft genome sequence based on Illumina short reads, and annotated approximately 17,000 genes. The P. lycopersici genome is closely related to hemibiotrophs and necrotrophs, in agreement with the phenotypic characteristics of the fungus and its lifestyle. Several gene families related to host–pathogen interactions are strongly represented, including those responsible for nutrient absorption, the detoxification of fungicides and plant cell wall degradation, the latter confirming that much of the genome is devoted to the pathogenic activity of the fungus. We did not find a MAT gene, which is consistent with the classification of P. lycopersici as an imperfect fungus, but we observed a significant expansion of the gene families associated with heterokaryon incompatibility (HI). Conclusions The P. lycopersici draft genome sequence provided insight into the molecular and genetic basis of the fungal lifestyle, characterizing previously unknown pathogenic behaviors and defining strategies that allow this asexual fungus to increase genetic diversity and to acquire new pathogenic traits. PMID:24767544

Methamphetamine Administration Modifies Leukocyte Proliferation and Cytokine Production in Murine Tissues

PubMed Central

Peerzada, Habibullah; Ghandi, Jay A.; Guimaraes, Allan J.; Nosanchuk, Joshua D.; Martinez, Luis R.

2013-01-01

Methamphetamine (METH) is a potent and highly addictive central nervous system (CNS) stimulant. Additionally, METH adversely impacts immunological responses, which might contribute to the higher rate and more rapid progression of certain infections in drug abusers. However no studies have shown the impact of METH on inflammation within specific organs, cellular participation and cytokine production. Using a murine model of METH administration, we demonstrated that METH modifies, with variable degrees, leukocyte recruitment and alters cellular mediators in the lungs, liver, spleen and kidneys of mice. Our findings demonstrate the pleotropic effects of METH on the immune response within diverse tissues. These alterations have profound implications on tissue homeostasis and the capacity of the host to respond to diverse insults, including invading pathogens. PMID:23518444

Trade-offs between acquired and innate immune defenses in humans

PubMed Central

McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

2016-01-01

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

Infection by Rhodococcus fascians maintains cotyledons as a sink tissue for the pathogen

PubMed Central

Dhandapani, Pragatheswari; Song, Jiancheng; Novak, Ondrej

2017-01-01

Background and Aims Pisum sativum L. (pea) seed is a source of carbohydrate and protein for the developing plant. By studying pea seeds inoculated by the cytokinin-producing bacterium, Rhodococcus fascians, we sought to determine the impact of both an epiphytic (avirulent) strain and a pathogenic strain on source–sink activity within the cotyledons during and following germination. Methods Bacterial spread was monitored microscopically, and real-time reverse transcription–quantitative PCR was used to determine the expression of cytokinin biosynthesis, degradation and response regulator gene family members, along with expression of family members of SWEET, SUT, CWINV and AAP genes – gene families identified initially in pea by transcriptomic analysis. The endogenous cytokinin content was also determined. Key Results The cotyledons infected by the virulent strain remained intact and turned green, while multiple shoots were formed and root growth was reduced. The epiphytic strain had no such marked impact. Isopentenyl adenine was elevated in the cotyledons infected by the virulent strain. Strong expression of RfIPT, RfLOG and RfCKX was detected in the cotyledons infected by the virulent strain throughout the experiment, with elevated expression also observed for PsSWEET, PsSUT and PsINV gene family members. The epiphytic strain had some impact on the expression of these genes, especially at the later stages of reserve mobilization from the cotyledons. Conclusions The pathogenic strain retained the cotyledons as a sink tissue for the pathogen rather than the cotyledon converting completely to a source tissue for the germinating plant. We suggest that the interaction of cytokinins, CWINVs and SWEETs may lead to the loss of apical dominance and the appearance of multiple shoots. PMID:27864224

Assessment of pathogen levels in stream water column and bed sediment of Merced River Watershed in California

NASA Astrophysics Data System (ADS)

Vaddella, V. K.; Pandey, P.; Biswas, S.; Lewis, D. J.

2014-12-01

Mitigating pathogen levels in surface water is crucial for protecting public health. According to the U.S. Environmental Protection Agency (US EPA), approximately 480,000 km of rivers/streams are contaminated in the U.S., and a major cause of contamination is elevated levels of pathogen/pathogen indicator. Many of past studies showed considerably higher pathogen levels in sediment bed than that of the stream water column in rivers. In order to improve the understanding of pathogen levels in rivers in California, we carried out an extensive pathogen monitoring study in four different watersheds (Bear Creek, Ingalsbe, Maxwell, and Yosemite watersheds) of Merced River. Stream water and streambed sediment samples were collected from 17 locations. Pathogen levels (E. coli O157:H7, Salmonella spp., and Listeria monocytogenes) were enumerated in streambed sediment and water column. In addition, the impacts of heat stress on pathogen survival were assessed by inoculating pathogens into the water and sediment samples for understanding the pathogen survival in stream water column and streambed sediment. The pathogen enumeration (in water column and sediment bed) results indicated that the E. coli O157:H7, Salmonella spp. and Listeria monocytogenes levels were non-detectable in the water column and streambed sediment. The results of heat stress (50◦ C for 180 minutes) test indicated a pathogen decay at one order of magnitude (108 cfu/ml to 107 cfu/ml). Nonetheless, higher pathogen levels (1.13 × 107 cfu/ml) after the heat stress study showed potential pathogen survival at higher temperature. Preliminary results of this study would help in understanding the impacts of elevated temperature on pathogen in stream environment. Further studies are required to test the long-term heat-stress impacts on pathogen survival.

The novel interaction between Phytophthora ramorum and wildfire elicits elevated ambrosia beetle landing rates on tanoak, Notholithocarpus densiflorus

Treesearch

Maia M. Beh; Margaret R. Metz; Steven J. Seybold; David M. Rizzo

2014-01-01

The 2008 wildfires in the Big Sur region of California’s central coast—the first to occur in forests impacted by Phytophthora ramorum, the non-native, invasive pathogen that causes sudden oak death—provided the rare opportunity to study the response of scolytid and other subcortical beetles to this novel disturbance interaction...

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

PubMed

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

Geographic variation in the response of Culex pipiens life history traits to temperature.

PubMed

Ruybal, Jordan E; Kramer, Laura D; Kilpatrick, A Marm

2016-02-29

Climate change is predicted to alter the transmission of many vector-borne pathogens. The quantitative impact of climate change is usually estimated by measuring the temperature-performance relationships for a single population of vectors, and then mapping this relationship across a range of temperatures or locations. However, life history traits of different populations often differ significantly. Specifically, performance across a range of temperatures is likely to vary due to local adaptation to temperature and other factors. This variation can cause spatial variation in pathogen transmission and will influence the impact of climate change on the transmission of vector-borne pathogens. We quantified variation in life history traits for four populations of Culex pipiens (Linnaeus) mosquitoes. The populations were distributed along altitudinal and latitudinal gradients in the eastern United States that spanned ~3 °C in mean summer temperature, which is similar to the magnitude of global warming expected in the next 3-5 decades. We measured larval and adult survival, development rate, and biting rate at six temperatures between 16 and 35 °C, in a common garden experiment. Temperature had strong and consistent non-linear effects on all four life history traits for all four populations. Adult female development time decreased monotonically with increasing temperature, with the largest decrease at cold temperatures. Daily juvenile and adult female survival also decreased with increasing temperature, but the largest decrease occurred at higher temperatures. There was significant among-population variation in the thermal response curves for the four life history traits across the four populations, with larval survival, adult survival, and development rate varying up to 45, 79, and 84 % among populations, respectively. However, variation was not correlated with local temperatures and thus did not support the local thermal adaptation hypothesis. These results suggest that the impact of climate change on vector-borne disease will be more variable than previous predictions, and our data provide an estimate of this uncertainty. In addition, the variation among populations that we observed will shape the response of vectors to changing climates.

Climate change triggers effects of fungal pathogens and insect herbivores on litter decomposition

NASA Astrophysics Data System (ADS)

Butenschoen, Olaf; Scheu, Stefan

2014-10-01

Increasing infestation by insect herbivores and pathogenic fungi in response to climate change will inevitably impact the amount and quality of leaf litter inputs into the soil. However, little is known on the interactive effect of infestation severity and climate change on litter decomposition, and no such study has been published for deciduous forests in Central Europe. We assessed changes in initial chemical quality of beech (Fagus sylvatica L.) and maple litter (Acer platanoides L.) in response to infestation by the gall midge Mikiola fagi Hart. and the pathogenic fungus Sawadaea tulasnei Fuckel, respectively, and investigated interactive effects of infestation severity, changes in temperature and soil moisture on carbon mineralization in a short-term laboratory study. We found that infestation by the gall midge M. fagi and the pathogenic fungus S. tulasnei significantly changed the chemical quality of beech and maple litter. Changes in element concentrations were generally positive and more pronounced, and if negative less pronounced for maple than beech litter most likely due to high quality fungal tissue remaining on litter after abscission. More importantly, alterations in litter chemical quality did not translate to distinct patterns of carbon mineralization at ambient conditions, but even low amounts of infested litter accelerated carbon mineralization at moderately increased soil moisture and in particular at higher temperature. Our results indicate that insect herbivores and fungal pathogens can markedly alter initial litter chemical quality, but that afterlife effects on carbon mineralization depend on soil moisture and temperature, suggesting that increased infestation severity under projected climate change potentially increases soil carbon release in deciduous forests in Central Europe.

Diversifying selection in the wheat stem rust fungus acts predominantly on pathogen-associated gene families and reveals candidate effectors

PubMed Central

Sperschneider, Jana; Ying, Hua; Dodds, Peter N.; Gardiner, Donald M.; Upadhyaya, Narayana M.; Singh, Karam B.; Manners, John M.; Taylor, Jennifer M.

2014-01-01

Plant pathogens cause severe losses to crop plants and threaten global food production. One striking example is the wheat stem rust fungus, Puccinia graminis f. sp. tritici, which can rapidly evolve new virulent pathotypes in response to resistant host lines. Like several other filamentous fungal and oomycete plant pathogens, its genome features expanded gene families that have been implicated in host-pathogen interactions, possibly encoding effector proteins that interact directly with target host defense proteins. Previous efforts to understand virulence largely relied on the prediction of secreted, small and cysteine-rich proteins as candidate effectors and thus delivered an overwhelming number of candidates. Here, we implement an alternative analysis strategy that uses the signal of adaptive evolution as a line of evidence for effector function, combined with comparative information and expression data. We demonstrate that in planta up-regulated genes that are rapidly evolving are found almost exclusively in pathogen-associated gene families, affirming the impact of host-pathogen co-evolution on genome structure and the adaptive diversification of specialized gene families. In particular, we predict 42 effector candidates that are conserved only across pathogens, induced during infection and rapidly evolving. One of our top candidates has recently been shown to induce genotype-specific hypersensitive cell death in wheat. This shows that comparative genomics incorporating the evolutionary signal of adaptation is powerful for predicting effector candidates for laboratory verification. Our system can be applied to a wide range of pathogens and will give insight into host-pathogen dynamics, ultimately leading to progress in strategies for disease control. PMID:25225496

Impact of methamphetamine on infection and immunity

PubMed Central

Salamanca, Sergio A.; Sorrentino, Edra E.; Nosanchuk, Joshua D.; Martinez, Luis R.

2015-01-01

The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation. PMID:25628526

Liver-inherent immune system: its role in blood-stage malaria

PubMed Central

Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A.

2014-01-01

The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main “antipodal” functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with “self” and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of “protective” autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system. PMID:25408684

Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence.

PubMed

Lamas, Bruno; Michel, Marie-Laure; Waldschmitt, Nadine; Pham, Hang-Phuong; Zacharioudaki, Vassiliki; Dupraz, Louise; Delacre, Myriam; Natividad, Jane M; Costa, Gregory Da; Planchais, Julien; Sovran, Bruno; Bridonneau, Chantal; Six, Adrien; Langella, Philippe; Richard, Mathias L; Chamaillard, Mathias; Sokol, Harry

2017-08-08

In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 ( CARD9 ), a key innate immunity gene, is required to shape a normal gut microbiota. Card9 -/- mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli . Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms. C. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9 -/- mice. To explore the impact of Card9 -/- microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9 -/- ( Card9 -/- →GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota-host immune system interactions were assessed by quantitative PCR analysis. CARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium -induced colitis was observed in Card9 -/- →GF mice. The microbiota of Card9 -/- mice failed to outcompete the monosaccharide-consuming C. rodentium , worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9 -/- mice. CARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Statistical Physics of T-Cell Development and Pathogen Specificity

NASA Astrophysics Data System (ADS)

Košmrlj, Andrej; Kardar, Mehran; Chakraborty, Arup K.

2013-04-01

In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial pathogens. Remarkably, the adaptive immune system mounts pathogen-specific responses, which can be recalled upon reinfection with the same pathogen. It is difficult to see how the adaptive immune system can be preprogrammed to respond specifically to a vast and unknown set of pathogens. Although major advances have been made in understanding pertinent molecular and cellular phenomena, the precise principles that govern many aspects of an immune response are largely unknown. We discuss complementary approaches from statistical mechanics and cell biology that can shed light on how key components of the adaptive immune system, T cells, develop to enable pathogen-specific responses against many diverse pathogens. The mechanistic understanding that emerges has implications for how host genetics may influence the development of T cells with differing responses to the human immunodeficiency virus (HIV) infection.

Laboratory simulation reveals significant impacts of ocean acidification on microbial community composition and host-pathogen interactions between the blood clam and Vibrio harveyi.

PubMed

Zha, Shanjie; Liu, Saixi; Su, Wenhao; Shi, Wei; Xiao, Guoqiang; Yan, Maocang; Liu, Guangxu

2017-12-01

It has been suggested that climate change may promote the outbreaks of diseases in the sea through altering the host susceptibility, the pathogen virulence, and the host-pathogen interaction. However, the impacts of ocean acidification (OA) on the pathogen components of bacterial community and the host-pathogen interaction of marine bivalves are still poorly understood. Therefore, 16S rRNA high-throughput sequencing and host-pathogen interaction analysis between blood clam (Tegillarca granosa) and Vibrio harveyi were conducted in the present study to gain a better understanding of the ecological impacts of ocean acidification. The results obtained revealed a significant impact of ocean acidification on the composition of microbial community at laboratory scale. Notably, the abundance of Vibrio, a major group of pathogens to many marine organisms, was significantly increased under ocean acidification condition. In addition, the survival rate and haemolytic activity of V. harveyi were significantly higher in the presence of haemolymph of OA treated T. granosa, indicating a compromised immunity of the clam and enhanced virulence of V. harveyi under future ocean acidification scenarios. Conclusively, the results obtained in this study suggest that future ocean acidification may increase the risk of Vibrio pathogen infection for marine bivalve species, such as blood clams. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling the intracellular pathogen-immune interaction with cure rate

NASA Astrophysics Data System (ADS)

Dubey, Balram; Dubey, Preeti; Dubey, Uma S.

2016-09-01

Many common and emergent infectious diseases like Influenza, SARS, Hepatitis, Ebola etc. are caused by viral pathogens. These infections can be controlled or prevented by understanding the dynamics of pathogen-immune interaction in vivo. In this paper, interaction of pathogens with uninfected and infected cells in presence or absence of immune response are considered in four different cases. In the first case, the model considers the saturated nonlinear infection rate and linear cure rate without absorption of pathogens into uninfected cells and without immune response. The next model considers the effect of absorption of pathogens into uninfected cells while all other terms are same as in the first case. The third model incorporates innate immune response, humoral immune response and Cytotoxic T lymphocytes (CTL) mediated immune response with cure rate and without absorption of pathogens into uninfected cells. The last model is an extension of the third model in which the effect of absorption of pathogens into uninfected cells has been considered. Positivity and boundedness of solutions are established to ensure the well-posedness of the problem. It has been found that all the four models have two equilibria, namely, pathogen-free equilibrium point and pathogen-present equilibrium point. In each case, stability analysis of each equilibrium point is investigated. Pathogen-free equilibrium is globally asymptotically stable when basic reproduction number is less or equal to unity. This implies that control or prevention of infection is independent of initial concentration of uninfected cells, infected cells, pathogens and immune responses in the body. The proposed models show that introduction of immune response and cure rate strongly affects the stability behavior of the system. Further, on computing basic reproduction number, it has been found to be minimum for the fourth model vis-a-vis other models. The analytical findings of each model have been exemplified by numerical simulations.

Current ecological understanding of fungal-like pathogens of fish: what lies beneath?

PubMed Central

Gozlan, Rodolphe E.; Marshall, Wyth L.; Lilje, Osu; Jessop, Casey N.; Gleason, Frank H.; Andreou, Demetra

2014-01-01

Despite increasingly sophisticated microbiological techniques, and long after the first discovery of microbes, basic knowledge is still lacking to fully appreciate the ecological importance of microbial parasites in fish. This is likely due to the nature of their habitats as many species of fish suffer from living beneath turbid water away from easy recording. However, fishes represent key ecosystem services for millions of people around the world and the absence of a functional ecological understanding of viruses, prokaryotes, and small eukaryotes in the maintenance of fish populations and of their diversity represents an inherent barrier to aquatic conservation and food security. Among recent emerging infectious diseases responsible for severe population declines in plant and animal taxa, fungal and fungal-like microbes have emerged as significant contributors. Here, we review the current knowledge gaps of fungal and fungal-like parasites and pathogens in fish and put them into an ecological perspective with direct implications for the monitoring of fungal fish pathogens in the wild, their phylogeography as well as their associated ecological impact on fish populations. With increasing fish movement around the world for farming, releases into the wild for sport fishing and human-driven habitat changes, it is expected, along with improved environmental monitoring of fungal and fungal-like infections, that the full extent of the impact of these pathogens on wild fish populations will soon emerge as a major threat to freshwater biodiversity. PMID:24600442

What is the Risk for Exposure to Vector-Borne Pathogens in United States National Parks?

PubMed Central

EISEN, LARS; WONG, DAVID; SHELUS, VICTORIA; EISEN, REBECCA J.

2015-01-01

United States national parks attract >275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. We assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal National Park Service documents and organismal databases. We conclude that, because of lack of systematic surveillance for vector-borne pathogens in national parks, the risk of pathogen exposure for staff and visitors is unclear. Existing data for vectors within national parks were not based on systematic collections and rarely include evaluation for pathogen infection. Extrapolation of human-based surveillance data from neighboring communities likely provides inaccurate estimates for national parks because landscape differences impact transmission of vector-borne pathogens and human-vector contact rates likely differ inside versus outside the parks because of differences in activities or behaviors. Vector-based pathogen surveillance holds promise to define when and where within national parks the risk of exposure to infected vectors is elevated. A pilot effort, including 5–10 strategic national parks, would greatly improve our understanding of the scope and magnitude of vector-borne pathogen transmission in these high-use public settings. Such efforts also will support messaging to promote personal protection measures and inform park visitors and staff of their responsibility for personal protection, which the National Park Service preservation mission dictates as the core strategy to reduce exposure to vector-borne pathogens in national parks. PMID:23540107

Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus.

PubMed

Pizzolla, Angela; Smith, Jeffery M; Brooks, Andrew G; Reading, Patrick C

2017-04-01

Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity. Therefore, a number of approaches have been developed to target specific PRRs in an effort to stimulate innate immunity and reduce disease in a variety of settings, including during influenza infections. Herein, we discuss progress in immunomodulation strategies designed to target cell-associated PRRs of the innate immune system, thereby, modifying innate responses to IAV infection and/or augmenting immune responses to influenza vaccines. © Society for Leukocyte Biology.

Climate and land-use change impact on faecal indicator bacteria in a temperate maritime catchment (the River Conwy, Wales)

NASA Astrophysics Data System (ADS)

Bussi, Gianbattista; Whitehead, Paul G.; Thomas, Amy R. C.; Masante, Dario; Jones, Laurence; Jack Cosby, B.; Emmett, Bridget A.; Malham, Shelagh K.; Prudhomme, Christel; Prosser, Havard

2017-10-01

Water-borne pathogen contamination from untreated sewage effluent and runoff from farms is a serious threat to the use of river water for drinking and commercial purposes, such as downstream estuarine shellfish industries. In this study, the impact of climate change and land-use change on the presence of faecal indicator bacteria in freshwater was evaluated, through the use of a recently-developed catchment-scale pathogen model. The River Conwy in Wales has been used as a case-study, because of the large presence of livestock in the catchment and the importance of the shellfish harvesting activities in its estuary. The INCA-Pathogens catchment model has been calibrated through the use of a Monte-Carlo-based technique, based on faecal indicator bacteria measurements, and then driven by an ensemble of climate projections obtained from the HadRM3-PPE model (Future Flow Climate) plus four land-use scenarios (current land use, managed ecosystem, abandonment and agricultural intensification). The results show that climate change is not expected to have a very large impact on average river flow, although it might alter its seasonality. The abundance of faecal indicator bacteria is expected to decrease in response to climate change, especially during the summer months, due to reduced precipitation, causing reduced runoff, and increased temperature, which enhances the bacterial die-off processes. Land-use change can also have a potentially large impact on pathogens. The "managed ecosystems" scenario proposed in this study can cause a reduction of 15% in average water faecal indicator bacteria and up to 30% in the 90th percentile of water faecal indicator bacteria, mainly due to the conversion of pasture land into grassland and the expansion of forest land. This study provides an example of how to assess the impacts of human interventions on the landscape, and what may be the extent of their effects, for other catchments where the human use of the natural resources in the uplands can jeopardise the use of natural resources downstream.

Systemic acquired tolerance to virulent bacterial pathogens in tomato.

PubMed

Block, Anna; Schmelz, Eric; O'Donnell, Phillip J; Jones, Jeffrey B; Klee, Harry J

2005-07-01

Recent studies on the interactions between plants and pathogenic microorganisms indicate that the processes of disease symptom development and pathogen growth can be uncoupled. Thus, in many instances, the symptoms associated with disease represent an active host response to the presence of a pathogen. These host responses are frequently mediated by phytohormones. For example, ethylene and salicylic acid (SA) mediate symptom development but do not influence bacterial growth in the interaction between tomato (Lycopersicon esculentum) and virulent Xanthomonas campestris pv vesicatoria (Xcv). It is not apparent why extensive tissue death is integral to a defense response if it does not have the effect of limiting pathogen proliferation. One possible function for this hormone-mediated response is to induce a systemic defense response. We therefore assessed the systemic responses of tomato to Xcv. SA- and ethylene-deficient transgenic lines were used to investigate the roles of these phytohormones in systemic signaling. Virulent and avirulent Xcv did induce a systemic response as evidenced by expression of defense-associated pathogenesis-related genes in an ethylene- and SA-dependent manner. This systemic response reduced cell death but not bacterial growth during subsequent challenge with virulent Xcv. This systemic acquired tolerance (SAT) consists of reduced tissue damage in response to secondary challenge with a virulent pathogen with no effect upon pathogen growth. SAT was associated with a rapid ethylene and pathogenesis-related gene induction upon challenge. SAT was also induced by infection with Pseudomonas syringae pv tomato. These data show that SAT resembles systemic acquired resistance without inhibition of pathogen growth.

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

PubMed Central

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants. PMID:29033963

Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens.

PubMed

Doublet, Vincent; Poeschl, Yvonne; Gogol-Döring, Andreas; Alaux, Cédric; Annoscia, Desiderato; Aurori, Christian; Barribeau, Seth M; Bedoya-Reina, Oscar C; Brown, Mark J F; Bull, James C; Flenniken, Michelle L; Galbraith, David A; Genersch, Elke; Gisder, Sebastian; Grosse, Ivo; Holt, Holly L; Hultmark, Dan; Lattorff, H Michael G; Le Conte, Yves; Manfredini, Fabio; McMahon, Dino P; Moritz, Robin F A; Nazzi, Francesco; Niño, Elina L; Nowick, Katja; van Rij, Ronald P; Paxton, Robert J; Grozinger, Christina M

2017-03-02

Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses. We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses. Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.

Combination vaccines against diarrheal diseases

PubMed Central

Venkatesan, Malabi M; Van de Verg, Lillian L

2015-01-01

Abstract Diarrheal diseases remain a leading cause of global childhood mortality and morbidity. Several recent epidemiological studies highlight the rate of diarrheal diseases in different parts of the world and draw attention to the impact on childhood growth and survival. Despite the well-documented global burden of diarrheal diseases, currently there are no combination diarrheal vaccines, only licensed vaccines for rotavirus and cholera, and Salmonella typhi-based vaccines for typhoid fever. The recognition of the impact of diarrheal episodes on infant growth, as seen in resource-poor countries, has spurred action from governmental and non-governmental agencies to accelerate research toward affordable and effective vaccines against diarrheal diseases. Both travelers and children in endemic countries will benefit from a combination diarrheal vaccine, but it can be argued that the greater proportion of any positive impact will be on the public health status of the latter. The history of combination pediatric vaccines indicate that monovalent or single disease vaccines are typically licensed first prior to formulation in a combination vaccine, and that the combinations themselves undergo periodic revision in response to need for improvement in safety or potential for wider coverage of important pediatric pathogens. Nevertheless combination pediatric vaccines have proven to be an effective tool in limiting or eradicating communicable childhood diseases worldwide. The landscape of diarrheal vaccine candidates indicates that there now several in active development that offer options for potential testing of combinations to combat those bacterial and viral pathogens responsible for the heaviest disease burden—rotavirus, ETEC, Shigella, Campylobacter, V. cholera and Salmonella. PMID:25891647

The role of probiotics in the poultry industry.

PubMed

Lutful Kabir, S M

2009-08-12

The increase of productivity in the poultry industry has been accompanied by various impacts, including emergence of a large variety of pathogens and bacterial resistance. These impacts are in part due to the indiscriminate use of chemotherapeutic agents as a result of management practices in rearing cycles. This review provides a summary of the use of probiotics for prevention of bacterial diseases in poultry, as well as demonstrating the potential role of probiotics in the growth performance and immune response of poultry, safety and wholesomeness of dressed poultry meat evidencing consumer's protection, with a critical evaluation of results obtained to date.

Understanding modern-day vaccines: what you need to know.

PubMed

Vetter, Volker; Denizer, Gülhan; Friedland, Leonard R; Krishnan, Jyothsna; Shapiro, Marla

2018-03-01

Vaccines are considered to be one of the greatest public health achievements of the last century. Depending on the biology of the infection, the disease to be prevented, and the targeted population, a vaccine may require the induction of different adaptive immune mechanisms to be effective. Understanding the basic concepts of different vaccines is therefore crucial to understand their mode of action, benefits, risks, and their potential real-life impact on protection. This review aims to provide healthcare professionals with background information about the main vaccine designs and concepts of protection in a simplified way to improve their knowledge and understanding, and increase their confidence in the science of vaccination ( Supplementary Material ). KEY MESSAGE Different vaccine designs, each with different advantages and limitations, can be applied for protection against a particular disease. Vaccines may contain live-attenuated pathogens, inactivated pathogens, or only parts of pathogens and may also contain adjuvants to stimulate the immune responses. This review explains the mode of action, benefits, risks and real-life impact of vaccines by highlighting key vaccine concepts. An improved knowledge and understanding of the main vaccine designs and concepts of protection will help support the appropriate use and expectations of vaccines, increase confidence in the science of vaccination, and help reduce vaccine hesitancy.

Assessing native small mammals' responses to an incipient invasion of beech bark disease through changes in seed production of American beech

Treesearch

Justin N. Rosemier; Andrew J. Storer

2011-01-01

Exotic tree diseases have direct impacts on their host and may have indirect effects on native fauna that rely on host tree species. For example, American beech (Fagus grandifolia [Ehrh.]) is a dominant overstory component throughout its range and, like all tree species, is vulnerable to a broad array of insects and pathogens. These pests include...

Metabolic host responses to infection by intracellular bacterial pathogens

PubMed Central

Eisenreich, Wolfgang; Heesemann, Jürgen; Rudel, Thomas; Goebel, Werner

2013-01-01

The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies. PMID:23847769

Mucosal immunity to pathogenic intestinal bacteria.

PubMed

Perez-Lopez, Araceli; Behnsen, Judith; Nuccio, Sean-Paul; Raffatellu, Manuela

2016-03-01

The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria.

Wildfire disturbance impacts on streamflow from western USA watersheds

NASA Astrophysics Data System (ADS)

Cadol, D.; Wine, M.; Makhnin, O.

2017-12-01

Worldwide rapid changes in climate overlaid on changing land management paradigms have dramatically altered ecological disturbance regimes worldwide including in western North America. Ecological disturbances impacted include woody encroachment, pest pathogen complexes, riparian forest changes, and wildfire. These disturbances impact the hydrologic cycle, though the nature of these impacts has been difficult to quantify. Perhaps the greatest challenge is that most basins worldwide are ungauged. Taking wildfire as a globally relevant example of a key ecological disturbance, even within gauged basins, post-wildfire hydrologic response is spatially and temporally variable, affected by a host of variables including fire frequency, area burned, and recovery trajectory. Hydrologic response to wildfire is further understood to be a non-linear function of watershed characteristics and climate. Here we provide a framework that utilizes remote sensing, statistical modeling, field measurements, and geospatial methods to provide first-order estimates of ecological disturbance hydrologic impacts. We apply this framework to compare ecological disturbance hydrologic impacts amongst selected watersheds in the western USA. Here we show that ecological disturbance impacts on hydrology are highly variable, and in many cases have an effect magnitude similar to that modeled for temperature and precipitation changes.

Subverting Toll-Like Receptor Signaling by Bacterial Pathogens

PubMed Central

McGuire, Victoria A.; Arthur, J. Simon C.

2015-01-01

Pathogenic bacteria are detected by pattern-recognition receptors (PRRs) expressed on innate immune cells, which activate intracellular signal transduction pathways to elicit an immune response. Toll-like receptors are, perhaps, the most studied of the PRRs and can activate the mitogen-activated protein kinase (MAPK) and Nuclear Factor-κB (NF-κB) pathways. These pathways are critical for mounting an effective immune response. In order to evade detection and promote virulence, many pathogens subvert the host immune response by targeting components of these signal transduction pathways. This mini-review highlights the diverse mechanisms that bacterial pathogens have evolved to manipulate the innate immune response, with a particular focus on those that target MAPK and NF-κB signaling pathways. Understanding the elaborate strategies that pathogens employ to subvert the immune response not only highlights the importance of these proteins in mounting effective immune responses, but may also identify novel approaches for treatment or prevention of infection. PMID:26648936

Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

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

Krishnan, A

2006-08-30

The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improvingmore » our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers/scientists in the area of host-pathogen interactions as well as policy makers from federal agencies. The main objectives of the workshop are: (1) to assess the current national needs, capabilities, near-term technologies, and future challenges in applying various diagnostics tools to public health and bio-defense; (2) to evaluate the utility and feasibility of host-response and pathogen biomarker profiling in the diagnosis and management of infectious diseases; and (3) to create a comprehensive developmental strategy from proof-of-concept, through validation, to deployment of appropriate advanced technology for the clinical/public health and bio-defense environments.« less

Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities

PubMed Central

2016-01-01

Infections remain a significant cause of morbidity and mortality in cancer patients. The differential diagnosis for these patients is often wide, and the timely selection of the right clinical tests can have a significant impact on their survival. However, laboratory findings with current methodologies are often negative, challenging clinicians and laboratorians to continue the search for the responsible pathogen. Novel methodologies are providing increased sensitivity and rapid turnaround time to results but also challenging our interpretation of what is a clinically significant pathogen in cancer patients. This minireview provides an overview of the most common infections in cancer patients and discusses some of the challenges and opportunities for the clinical microbiologist supporting the care of cancer patients. PMID:27280421

The enemy within us: lessons from the 2011 European Escherichia coli O104:H4 outbreak.

PubMed

Karch, Helge; Denamur, Erick; Dobrindt, Ulrich; Finlay, B Brett; Hengge, Regine; Johannes, Ludgers; Ron, Eliora Z; Tønjum, Tone; Sansonetti, Philippe J; Vicente, Miguel

2012-09-01

In response to the 2011 European health alert caused by a pathogenic Escherichia coli O104:H4 outbreak, the European Academy of Microbiology (EAM), established by the Federation of European Microbiological Societies (FEMS), convened a meeting in Paris on November 30th, 2011 on 'EHEC infection and control' attended by world renowned experts in pathogenic E. coli. The major aims of this group were to review the scientific issues raised by the outbreak, to assess the handling of the crisis at the scientific and political levels, and to propose future actions. Several conclusions, which will have impact on future potential E. coli outbreaks, are outlined here. Copyright © 2012 EMBO Molecular Medicine.

Lack of Original Antigenic Sin in Recall CD8+ T Cell Responses

PubMed Central

Zehn, Dietmar; Turner, Michael J.; Lefrançois, Leo; Bevan, Michael J.

2010-01-01

In the real world, mice and men are not immunologically naive, having been exposed to numerous antigenic challenges. Prior infections sometimes negatively impact the response to a subsequent infection. This can occur in serial infections with pathogens sharing cross-reactive Ags. At the T cell level it has been proposed that preformed memory T cells, which cross-react with low avidity to epitopes presented in subsequent infections, dampen the response of high-avidity T cells. We investigated this with a series of related MHC class-I restricted Ags expressed by bacterial and viral pathogens. In all cases, we find that high-avidity CD8+ T cell precursors, either naive or memory, massively expand in secondary cross-reactive infections to dominate the response over low-avidity memory T cells. This holds true even when >10% of the CD8+ T cell compartment consists of memory T cells that cross-react weakly with the rechallenge ligand. Occasionally, memory cells generated by low-avidity stimulation in a primary infection recognize a cross-reactive epitope with high avidity and contribute positively to the response to a second infection. Taken together, our data show that the phenomenon of original antigenic sin does not occur in all heterologous infections. PMID:20439913

Prevention and control strategies for ticks and pathogen transmission.

PubMed

de La Fuente, J; Kocan, K M; Contreras, M

2015-04-01

Ticks and tick-borne pathogens have evolved together, resulting in a complex relationship in which the pathogen's life cycle is perfectly coordinated with the tick's feeding cycle, and the tick can harbour high pathogen levels without affecting its biology. Tick-borne diseases (TBDs) continue to emerge and/or spread, and pose an increasing threatto human and animal health. The disruptive impacts of global change have resulted in ecosystem instability and the future outcomes of management and control programmes for ticks and TBDs are difficult to predict. In particular, the selection of acaricide-resistant ticks has reduced the value of acaricides as a sole means of tick control. Vaccines provide an alternative control method, but the use of tick vaccines has not advanced since the first vaccines were registered in the early 1990s. An understanding of the complex molecular relationship between hosts, ticks and pathogens and the use of systems biology and vaccinomics approaches are needed to discover proteins with the relevant biological function in tick feeding, reproduction, development, immune response, the subversion of host immunity and pathogen transmission, all of which mediate tick and pathogen success. The same approaches will also be required to characterise candidate protective antigens and to validate vaccine formulations. Tick vaccines with a dual effect on tick infestations and pathogen transmission could reduce both tick infestations and their vector capacity for humans, animals and reservoir hosts. The development of integrated tick control strategies, including vaccines and synthetic and botanical acaricides, in combination with managing drug resistance and educating producers, should lead to the sustainable control of ticks and TBDs.

Interacting Symbionts and Immunity in the Amphibian Skin Mucosome Predict Disease Risk and Probiotic Effectiveness

PubMed Central

Woodhams, Douglas C.; Brandt, Hannelore; Baumgartner, Simone; Kielgast, Jos; Küpfer, Eliane; Tobler, Ursina; Davis, Leyla R.; Schmidt, Benedikt R.; Bel, Christian; Hodel, Sandro; Knight, Rob; McKenzie, Valerie

2014-01-01

Pathogenesis is strongly dependent on microbial context, but development of probiotic therapies has neglected the impact of ecological interactions. Dynamics among microbial communities, host immune responses, and environmental conditions may alter the effect of probiotics in human and veterinary medicine, agriculture and aquaculture, and the proposed treatment of emerging wildlife and zoonotic diseases such as those occurring on amphibians or vectored by mosquitoes. Here we use a holistic measure of amphibian mucosal defenses to test the effects of probiotic treatments and to assess disease risk under different ecological contexts. We developed a non-invasive assay for antifungal function of the skin mucosal ecosystem (mucosome function) integrating host immune factors and the microbial community as an alternative to pathogen exposure experiments. From approximately 8500 amphibians sampled across Europe, we compared field infection prevalence with mucosome function against the emerging fungal pathogen Batrachochytrium dendrobatidis. Four species were tested with laboratory exposure experiments, and a highly susceptible species, Alytes obstetricans, was treated with a variety of temperature and microbial conditions to test the effects of probiotic therapies and environmental conditions on mucosome function. We found that antifungal function of the amphibian skin mucosome predicts the prevalence of infection with the fungal pathogen in natural populations, and is linked to survival in laboratory exposure experiments. When altered by probiotic therapy, the mucosome increased antifungal capacity, while previous exposure to the pathogen was suppressive. In culture, antifungal properties of probiotics depended strongly on immunological and environmental context including temperature, competition, and pathogen presence. Functional changes in microbiota with shifts in temperature provide an alternative mechanistic explanation for patterns of disease susceptibility related to climate beyond direct impact on host or pathogen. This nonlethal management tool can be used to optimize and quickly assess the relative benefits of probiotic therapies under different climatic, microbial, or host conditions. PMID:24789229

Controlling hormone signaling is a plant and pathogen challenge for growth and survival.

PubMed

López, Miguel Angel; Bannenberg, Gerard; Castresana, Carmen

2008-08-01

Plants and pathogens have continuously confronted each other during evolution in a battle for growth and survival. New advances in the field have provided fascinating insights into the mechanisms that have co-evolved to gain a competitive advantage in this battle. When plants encounter an invading pathogen, not only responses signaled by defense hormones are activated to restrict pathogen invasion, but also the modulation of additional hormone pathways is required to serve other purposes, which are equally important for plant survival, such as re-allocation of resources, control of cell death, regulation of water stress, and modification of plant architecture. Notably, pathogens can counteract both types of responses as a strategy to enhance virulence. Pathogens regulate production and signaling responses of plant hormones during infection, and also produce phytohormones themselves to modulate plant responses. These results indicate that hormone signaling is a relevant component in plant-pathogen interactions, and that the ability to dictate hormonal directionality is critical to the outcome of an interaction.

Pathogen-Sensing and Regulatory T Cells: Integrated Regulators of Immune Responses

PubMed Central

Grossman, Zvi; Paul, William E.

2014-01-01

We present the concept that pathogen-sensing and Tregs mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells. Normally, conventional CD4 T cells recognizing their cognate antigen-presented by a dendritic cell will respond only if the dendritic cell also receives a signal through its pathogen-sensing/ danger / adjuvant recognition systems (the pathogen-sensing triad). However, if Tregs capable of interacting with the same DC are absent, dendritic cells are competent to present antigens, both foreign and self, even without the stimulation provided by the pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is also presenting antigen to a conventional CD4 T cell will prevent such responses but a signal delivered by a member of the pathogen-sensing traid will overcome the Tregs’inhibitory action and will allow responses to go forward. These considerations take on special meaning for responses to “weak antigens” such as many of the antigens displayed by spontaneous human tumors. PMID:24894087

Rhizospheric soil and root endogenous fungal diversity and composition in response to continuous Panax notoginseng cropping practices.

PubMed

Tan, Yong; Cui, Yinshan; Li, Haoyu; Kuang, Anxiu; Li, Xiaoran; Wei, Yunlin; Ji, Xiuling

2017-01-01

Rhizosphere and endophytic fungal communities are considered critically important for plant health and soil fertility. In response to continuous cropping, Panax notoginseng becomes vulnerable to attack by fungal pathogens. In the present study, culture-independent Illumina MiSeq was used to investigate the rhizospheric and root endophytic fungi in response to continuous Panax notoginseng cropping practices. The results demonstrated that fungal diversity is increased inside the roots and in rhizospheric. Ascomycota, Zygomycota, Basidiomycota and Chytridiomycota were the dominant phyla detected during the continuous cropping of Panax notoginseng. The fungal diversity in the rhizospheric soil and roots of root-rot P. notoginseng plants are less than that of healthy plants in the same cultivating year, thus showing that root-rot disease also affects the community structure and diversity of rhizospheric and root endophytic fungi. Similarities in the major fungal components show that endophytic fungal communities are similar to rhizospheric soil fungal community based on a specialized subset of organisms. Canonical correspondence analysis on the fungal communities in root-rot rhizospheric from both healthy plants and rotation soils reveals that the soil pH and organic matter have the greatest impact upon the microbial community composition during continuous cropping, whereas soil nutrition status does not significantly affect the fungal community composition in response to continuous cropping practices. In addition, the results suggest that the unclassified genera Leotiomycetes, Cylindrocarpon, Fusarium and Mycocentrospora are shown as the potential pathogens which are responsible for the obstacles in continuous cropping of P. notoginseng. Further exploration of these potential pathogens might be useful for the biological control of continuous cropping of P. notoginseng. Copyright © 2016 Elsevier GmbH. All rights reserved.

Fungal-mediated mortality explains the different effects of dung leachates on the germination response of grazing increaser and decreaser species

NASA Astrophysics Data System (ADS)

Carmona, Carlos P.; Navarro, Elena; Peco, Begoña

2016-01-01

Depending on their response to grazing, grassland species can be categorized as grazing increasers or decreasers. Grazing by livestock includes several different activities that can impact species differently. Recent evidence suggest that one of these actions, dung deposition, can reduce the germinative performance of decreaser species, thus favouring increasers. The present study tested the hypothesis that decreased germinative success of decreaser species is caused by a greater activity of fungal pathogens under the influence of dung leachates. We performed a phytotron experiment analysing the germination and fungal infections of fourteen species from Mediterranean grasslands. Species were grouped into phylogenetically-related pairs, composed of an increaser and a decreaser species. Seeds of each species were germinated under four different treatments (control, dung leachate addition, fungicide addition and dung leachate and fungicide addition), and the differences in germination percentage, germination speed and infection rate between each increaser species and its decreaser counterpart were analysed. Decreaser species were more affected by mortality than increaser ones, and these differences were higher under the presence of dung leachates. The differences in germinative performance after excluding the effect of seed mortality did not differ between treatments, showing that the main mechanism by which dung leachates favour increaser species is through increased mortality of the seeds of decreaser species. Drastic reductions in the number of dead seeds in the treatments including fungicide addition further revealed that fungal pathogens are responsible for these differences between species with different grazing response. The different vulnerabilities of increaser and decreaser species to the increased activity of fungal pathogens under the presence of dung leachates seems the main reason behind the differential effect of these leachates on species with different grazing response.

Cellular Responses in Sea Fan Corals: Granular Amoebocytes React to Pathogen and Climate Stressors

PubMed Central

Mydlarz, Laura D.; Holthouse, Sally F.; Peters, Esther C.; Harvell, C. Drew

2008-01-01

Background Climate warming is causing environmental change making both marine and terrestrial organisms, and even humans, more susceptible to emerging diseases. Coral reefs are among the most impacted ecosystems by climate stress, and immunity of corals, the most ancient of metazoans, is poorly known. Although coral mortality due to infectious diseases and temperature-related stress is on the rise, the immune effector mechanisms that contribute to the resistance of corals to such events remain elusive. In the Caribbean sea fan corals (Anthozoa, Alcyonacea: Gorgoniidae), the cell-based immune defenses are granular acidophilic amoebocytes, which are known to be involved in wound repair and histocompatibility. Methodology/Principal Findings We demonstrate for the first time in corals that these cells are involved in the organismal response to pathogenic and temperature stress. In sea fans with both naturally occurring infections and experimental inoculations with the fungal pathogen Aspergillus sydowii, an inflammatory response, characterized by a massive increase of amoebocytes, was evident near infections. Melanosomes were detected in amoebocytes adjacent to protective melanin bands in infected sea fans; neither was present in uninfected fans. In naturally infected sea fans a concurrent increase in prophenoloxidase activity was detected in infected tissues with dense amoebocytes. Sea fans sampled in the field during the 2005 Caribbean Bleaching Event (a once-in-hundred-year climate event) responded to heat stress with a systemic increase in amoebocytes and amoebocyte densities were also increased by elevated temperature stress in lab experiments. Conclusions/Significance The observed amoebocyte responses indicate that sea fan corals use cellular defenses to combat fungal infection and temperature stress. The ability to mount an inflammatory response may be a contributing factor that allowed the survival of even infected sea fan corals during a stressful climate event. PMID:18364996

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

PubMed

Vasques, Gabriela A; Funari, Mariana F A; Ferreira, Frederico M; Aza-Carmona, Miriam; Sentchordi-Montané, Lucia; Barraza-García, Jimena; Lerario, Antonio M; Yamamoto, Guilherme L; Naslavsky, Michel S; Duarte, Yeda A O; Bertola, Debora R; Heath, Karen E; Jorge, Alexander A L

2018-02-01

Genetic evaluation has been recognized as an important tool to elucidate the causes of growth disorders. To investigate the cause of short stature and to determine the phenotype of patients with IHH mutations, including the response to recombinant human growth hormone (rhGH) therapy. We studied 17 families with autosomal-dominant short stature by using whole exome sequencing and screened IHH defects in 290 patients with growth disorders. Molecular analyses were performed to evaluate the potential impact of N-terminal IHH variants. We identified 10 pathogenic or possibly pathogenic variants in IHH, an important regulator of endochondral ossification. Molecular analyses revealed a smaller potential energy of mutated IHH molecules. The allele frequency of rare, predicted to be deleterious IHH variants found in short-stature samples (1.6%) was higher than that observed in two control cohorts (0.017% and 0.08%; P < 0.001). Identified IHH variants segregate with short stature in a dominant inheritance pattern. Affected individuals typically manifest mild disproportional short stature with a frequent finding of shortening of the middle phalanx of the fifth finger. None of them have classic features of brachydactyly type A1, which was previously associated with IHH mutations. Five patients heterozygous for IHH variants had a good response to rhGH therapy. The mean change in height standard deviation score in 1 year was 0.6. Our study demonstrated the association of pathogenic variants in IHH with short stature with nonspecific skeletal abnormalities and established a frequent cause of growth disorder, with a preliminary good response to rhGH. Copyright © 2017 Endocrine Society

Plant response to biotic stress: Is there a common epigenetic response during plant-pathogenic and symbiotic interactions?

PubMed

Zogli, Prince; Libault, Marc

2017-10-01

Plants constantly interact with pathogenic and symbiotic microorganisms. Recent studies have revealed several regulatory mechanisms controlling these interactions. Among them, the plant defense system is activated not only in response to pathogenic, but also in response to symbiotic microbes. Interestingly, shortly after symbiotic microbial recognition, the plant defense system is suppressed to promote plant infection by symbionts. Research studies have demonstrated the influence of the plant epigenome in modulating both pathogenic and symbiotic plant-microbe interactions, thereby influencing plant survival, adaptation and evolution of the plant response to microbial infections. It is however unclear if plant pathogenic and symbiotic responses share similar epigenomic profiles or if epigenomic changes differentially regulate plant-microbe symbiosis and pathogenesis. In this mini-review, we provide an update of the current knowledge of epigenomic control on plant immune responses and symbiosis, with a special attention being paid to knowledge gap and potential strategies to fill-in the missing links. Copyright © 2017 Elsevier B.V. All rights reserved.

Estimating the impact on health of poor reliability of drinking water interventions in developing countries.

PubMed

Hunter, Paul R; Zmirou-Navier, Denis; Hartemann, Philippe

2009-04-01

Recent evidence suggests that many improved drinking water supplies suffer from poor reliability. This study investigates what impact poor reliability may have on achieving health improvement targets. A Quantitative Microbiological Risk Assessment was conducted of the impact of interruptions in water supplies that forced people to revert to drinking raw water. Data from the literature were used to construct models on three waterborne pathogens common in Africa: Rotavirus, Cryptosporidium and Enterotoxigenic E. coli. Risk of infection by the target pathogens is substantially greater on days that people revert to raw water consumption. Over the course of a few days raw water consumption, the annual health benefits attributed to consumption of water from an improved supply will be almost all lost. Furthermore, risk of illness on days drinking raw water will fall substantially on very young children who have the highest risk of death following infection. Agencies responsible for implementing improved drinking water provision will not make meaningful contributions to public health targets if those systems are subject to poor reliability. Funders of water quality interventions in developing countries should put more effort into auditing whether interventions are sustainable and whether the health benefits are being achieved.

The role of nitric oxide in the interaction of Arabidopsis thaliana with the biotrophic fungi, Golovinomyces orontii and Erysiphe pisi

PubMed Central

Schlicht, Markus; Kombrink, Erich

2013-01-01

Powdery mildews are a diverse group of pathogenic fungi that can infect a large number of plant species, including many economically important crops. However, basic and applied research on these devastating diseases has been hampered by the obligate biotrophic lifestyle of the pathogens, which require living host cells for growth and reproduction, and lacking genetic and molecular tools for important host plants. The establishment of Arabidopsis thaliana as a host of different powdery mildew species allowed pursuing new strategies to study the molecular mechanisms governing these complex plant–pathogen interactions. Nitric oxide (NO) has emerged as an important signaling molecule in plants, which is produced upon infection and involved in activation of plant immune responses. However, the source and pathway of NO production and its precise function in the regulatory network of reactions leading to resistance is still unknown. We studied the response of Arabidopsis thaliana to infection with the adapted powdery mildew, Golovinomyces orontii (compatible interaction) and the non-adapted, Erysiphe pisi (incompatible interaction). We observed that NO accumulated rapidly and transiently at infection sites and we established a correlation between the resistance phenotype and the amount and timing of NO production. Arabidopsis mutants with defective immune response accumulated lower NO levels compared to wild type. Conversely, increased NO levels, generated by treatment with chemicals or expression of a NO-synthesizing enzyme, resulted in enhanced resistance, but only sustained NO production prevented excessive leaf colonization by the fungus, which was not achieved by a short NO burst although this reduced the initial penetration success. By contrast, lowered NO levels did not impair the ultimate resistance phenotype. Although our results suggest a function of NO in mediating plant immune responses, a direct impact on pathogen growth and development cannot be excluded. PMID:24058365

Ubiquitin Ligases and Deubiquitinating Enzymes in CD4+ T Cell Effector Fate Choice and Function.

PubMed

Layman, Awo A K; Oliver, Paula M

2016-05-15

The human body is exposed to potentially pathogenic microorganisms at barrier sites such as the skin, lungs, and gastrointestinal tract. To mount an effective response against these pathogens, the immune system must recruit the right cells with effector responses that are appropriate for the task at hand. Several types of CD4(+) T cells can be recruited, including Th cells (Th1, Th2, and Th17), T follicular helper cells, and regulatory T cells. These cells help to maintain normal immune homeostasis in the face of constantly changing microbes in the environment. Because these cells differentiate from a common progenitor, the composition of their intracellular milieu of proteins changes to appropriately guide their effector function. One underappreciated process that impacts the levels and functions of effector fate-determining factors is ubiquitylation. This review details our current understanding of how ubiquitylation regulates CD4(+) T cell effector identity and function. Copyright © 2016 by The American Association of Immunologists, Inc.

The personal touch: strategies toward personalized vaccines and predicting immune responses to them

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Haralambieva, Iana H.; Poland, Gregory A.

2014-01-01

The impact of vaccines on public health and well-being has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as: hepatitis C, malaria, or tuberculosis, as well as new and re-emerging pathogens for which lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population. PMID:24702429

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

PubMed

Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

2018-03-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

PubMed Central

2018-01-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. PMID:29436184

Survey of Armillaria spp. in the Oregon East Cascades: Baseline data for predicting climatic influences on Armillaria root disease

Treesearch

J. W. Hanna; A. L. Smith; H. M. Maffei; M.-S. Kim; N. B. Klopfenstein

2008-01-01

Root disease pathogens, such as Armillaria solidipes Peck (recently recognized older name for A. ostoyae), will likely have increasing impacts to forest ecosystems as trees undergo stress due to climate change. Before we can predict future impacts of root disease pathogens, we must first develop an ability to predict current distributions of the pathogens (and their...

Planning for compliance: OSHA's bloodborne pathogen rule.

PubMed

Bednar, B; Duke, M C

1990-11-01

Overall, the bloodborne pathogen rule constitutes a reasonable response to a significant threat to workplace safety. The risks to dialysis workers from HBV and HIV must be minimized or eliminated and the rule is generally consistent with the consensus approach. Unfortunately for dialysis providers, the rule is not exempt from the law of unintended consequences: government regulation will always have impact beyond its object. Promulgation of the final rule will immediately increase the expenses of dialysis providers. Additionally, the enormity of the HBV and HIV problem coupled with the open-ended nature of the rule's key provisions will almost certainly bring additional costs. So long as dialysis reimbursement remains flat, the unintended consequence of the bloodborne pathogen rule may be to quicken the pace of consolidation in the dialysis service market. The added burden of compliance may be too much for small independent facilities. Only large chains may have the resources to comply and survive. To forestall this effect and to provide employees with maximum protection, all dialysis providers should plan now for compliance.

Biosafety and biosecurity in veterinary laboratories

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

Finley, Melissa R.; Astuto-Gribble, Lisa M.; Brass, Van Hildren

Here, with recent outbreaks of MERS-Cov, Anthrax, Nipah, and Highly Pathogenic Avian Influenza, much emphasis has been placed on rapid identification of infectious agents globally. As a result, laboratories are building capacity, conducting more advanced and sophisticated research, increasing laboratory staff, and establishing collections of dangerous pathogens in an attempt to reduce the impact of infectious disease outbreaks and characterize disease causing agents. With this expansion, the global laboratory community has started to focus on laboratory biosafety and biosecurity to prevent the accidental and/or intent ional release o f these agents. Laboratory biosafety and biosecurity systems are used around themore » world to help mit igate the risks posed by dangerous pathogens in the laboratory. Veterinary laboratories carry unique responsibilities to workers and communities to safely and securely handle disease causing microorganisms. Many microorganisms studied in veterinary laboratories not only infect animals, but also have the potential to infect humans. This paper will discuss the fundamentals of laboratory biosafety and biosecurity.« less

Pathogen recognition in the innate immune response.

PubMed

Kumar, Himanshu; Kawai, Taro; Akira, Shizuo

2009-04-28

Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)-like receptors] and NLRs (Nod-like receptors). These receptors recognize pathogens or pathogen-derived products in different cellular compartments, such as the plasma membrane, the endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and instruct pathogen-specific adaptive immune responses. In the present review, we will discuss the recent progress in the study of pathogen recognition by TLRs, RLRs and NLRs and their signalling pathways.

New activity of yamamarin, an insect pentapeptide, on immune system of mealworm, Tenebrio molitor.

PubMed

Walkowiak-Nowicka, K; Nowicki, G; Kuczer, M; Rosiński, G

2017-09-12

In insects, two types of the immune responses, cellular and humoral, constitute a defensive barrier against various parasites and pathogens. In response to pathogens, insects produce a wide range of immune agents that act on pathogens directly, such as cecropins or lysozyme, or indirectly by the stimulation of hemocyte migration or by increasing phenoloxidase (PO) activity. Recently, many new immunologically active substances from insects, such as peptides and polypeptides, have been identified. Nevertheless, in the most cases, their physiological functions are not fully known. One such substance is yamamarin - a pentapeptide isolated from the silk moth Antheraea yamamai. This yamamarin possesses strong antiproliferative properties and is probably involved in diapause regulation. Here, we examined the immunotropic activity of yamamarin by testing its impact on selected functions of the immune system in heterologous bioassays with the beetle Tenebrio molitor, commonly known as a stored grains pest. Our results indicate that the pentapeptide affects the activity of immune processes in the beetle. We show that yamamarin induces changes in both humoral and cellular responses. The yamamarin increases the activity of PO, as well as causes changes in the hemocyte cytoskeleton and stimulates phagocytic activity. We detected an increased number of apoptotic hemocytes, however after the yamamarin injection, no significant variations in the antibacterial activity in the hemolymph were observed. The obtained data suggest that yamamarin could be an important controller of the immune system in T. molitor.

Protective Microbiota: From Localized to Long-Reaching Co-Immunity

PubMed Central

Chiu, Lynn; Bazin, Thomas; Truchetet, Marie-Elise; Schaeverbeke, Thierry; Delhaes, Laurence; Pradeu, Thomas

2017-01-01

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota. PMID:29270167

Plasmodesmal regulation during plant-pathogen interactions.

PubMed

Cheval, Cecilia; Faulkner, Christine

2018-01-01

Contents Summary 62 I. Introduction 62 II. Plasmodesmal regulation is an innate defence response 63 III. Reactive oxygen species regulate plasmodesmal function 63 IV. Plasmodesmal regulation by and of defence-associated small molecules 64 V. Plasmodesmata facilitate systemic defence signalling 64 VI. Virulent pathogens exploit plasmodesmata 66 VII. Outlook 66 Acknowledgements 66 References 66 SUMMARY: Plasmodesmata (PD) are plasma membrane-lined pores that connect neighbouring plant cells, bridging the cell wall and establishing cytoplasmic and membrane continuity between cells. PD are dynamic structures regulated by callose deposition in a variety of stress and developmental contexts. This process crudely controls the aperture of the pore and thus the flux of molecules between cells. During pathogen infection, plant cells initiate a range of immune responses and it was recently identified that, following perception of fungal and bacterial pathogens, plant cells initially close their PD. Systemic defence responses depend on the spread of signals between cells, raising questions about whether PD are in different functional states during different immune responses. It is well established that viral pathogens exploit PD to spread between cells, but it has more recently been identified that protein effectors secreted by fungal pathogens can spread between host cells via PD. It is possible that many classes of pathogens specifically target PD to aid infection, which would infer antagonistic regulation of PD by host and pathogen. How PD regulation benefits both host immune responses and pathogen infection is an important question and demands that we examine the multicellular nature of plant-pathogen interactions. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

The Arabidopsis miR396 mediates pathogen-associated molecular pattern-triggered immune responses against fungal pathogens

PubMed Central

Soto-Suárez, Mauricio; Baldrich, Patricia; Weigel, Detlef; Rubio-Somoza, Ignacio; San Segundo, Blanca

2017-01-01

MicroRNAs (miRNAs) play a pivotal role in regulating gene expression during plant development. Although a substantial fraction of plant miRNAs has proven responsive to pathogen infection, their role in disease resistance remains largely unknown, especially during fungal infections. In this study, we screened Arabidopsis thaliana lines in which miRNA activity has been reduced using artificial miRNA target mimics (MIM lines) for their response to fungal pathogens. Reduced activity of miR396 (MIM396 plants) was found to confer broad resistance to necrotrophic and hemibiotrophic fungal pathogens. MiR396 levels gradually decreased during fungal infection, thus, enabling its GRF (GROWTH-REGULATING FACTOR) transcription factor target genes to trigger host reprogramming. Pathogen resistance in MIM396 plants is based on a superactivation of defense responses consistent with a priming event during pathogen infection. Notably, low levels of miR396 are not translated in developmental defects in absence of pathogen challenge. Our findings support a role of miR396 in regulating plant immunity, and broaden our knowledge about the molecular players and processes that sustain defense priming. That miR396 modulates innate immunity without growth costs also suggests fine-tuning of miR396 levels as an effective biotechnological means for protection against pathogen infection. PMID:28332603

Nucleic Acid-Based Detection and Identification of Bacterial and Fungal Plant Pathogens - Final Report

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

Kingsley, Mark T.

2001-03-13

The threat to American interests from terrorists is not limited to attacks against humans. Terrorists might seek to inflict damage to the U.S. economy by attacking our agricultural sector. Infection of commodity crops by bacterial or fungal crop pathogens could adversely impact U.S. agriculture, either directly from damage to crops or indirectly from damage to our ability to export crops suspected of contamination. Recognizing a terrorist attack against U.S. agriculture, to be able to prosecute the terrorists, is among the responsibilities of the members of Hazardous Material Response Unit (HMRU) of the Federal Bureau of Investigation (FBI). Nucleic acid analysismore » of plant pathogen strains by the use of polymerase chain reaction (PCR) amplification techniques is a powerful method for determining the exact identity of pathogens, as well as their possible region of origin. This type of analysis, however, requires that PCR assays be developed specific to each particular pathogen strain, and analysis protocols developed that are specific to the particular instrument used for detection. The objectives of the work described here were threefold: 1) to assess the potential terrorist threat to U.S. agricultural crops, 2) to determine whether suitable assays exist to monitor that threat, and 3) where assays are needed for priority plant pathogen threats, to modify or develop those assays for use by specialists at the HMRU. The assessment of potential threat to U.S. commodity crops and the availability of assays for those threats were described in detail in the Technical Requirements Document (9) and will be summarized in this report. This report addresses development of specific assays identified in the Technical Requirements Document, and offers recommendations for future development to ensure that HMRU specialists will be prepared with the PCR assays they need to protect against the threat of economic terrorism.« less

Nucleic Acid-Based Detection and Identification of Bacterial and Fungal Plant Pathogens - Final Report

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

Kingsley, Mark T

2001-03-13

The threat to American interests from terrorists is not limited to attacks against humans. Terrorists might seek to inflict damage to the U.S. economy by attacking our agricultural sector. Infection of commodity crops by bacterial or fungal crop pathogens could adversely impact U.S. agriculture, either directly from damage to crops or indirectly from damage to our ability to export crops suspected of contamination. Recognizing a terrorist attack against U.S. agriculture, to be able to prosecute the terrorists, is among the responsibilities of the members of Hazardous Material Response Unit (HMRU) of the Federal Bureau of Investigation (FBI). Nucleic acid analysismore » of plant pathogen strains by the use of polymerase chain reaction (PCR) amplification techniques is a powerful method for determining the exact identity of pathogens, as well as their possible region of origin. This type of analysis, however, requires that PCR assays be developed specific to each particular pathogen strain, an d analysis protocols developed that are specific to the particular instrument used for detection. The objectives of the work described here were threefold: (1) to assess the potential terrorist threat to U.S. agricultural crops, (2) to determine whether suitable assays exist to monitor that threat, and (3) where assays are needed for priority plant pathogen threats, to modify or develop those assays for use by specialists at the HMRU. The assessment of potential threat to U.S. commodity crops and the availability of assays for those threats were described in detail in the Technical Requirements Document (9) and will be summarized in this report. This report addresses development of specific assays identified in the Technical Requirements Document, and offers recommendations for future development to ensure that HMRU specialists will be prepared with the PCR assays they need to protect against the threat of economic terrorism.« less

The impact of a moderate chronic temperature increase on spleen immune-relevant gene transcription depends on whether Atlantic cod (Gadus morhua) are stimulated with bacterial versus viral antigens.

PubMed

Hori, Tiago S; Gamperl, A Kurt; Nash, Gord; Booman, Marije; Barat, Ashoktaru; Rise, Matthew L

2013-10-01

Exposure to elevated temperature is an inherent feature of Atlantic cod (Gadus morhua) sea-cage culture in some regions (e.g., Newfoundland) and may also become an increasingly prevalent challenge for wild fish populations because of accelerated climate change. Therefore, understanding how elevated temperatures impacts the immune response of this commercially important species may help to reduce the potential negative impacts of such challenges. Previously, we investigated the impacts of moderately elevated temperature on the antiviral responses of Atlantic cod (Hori et al. 2012) and reported that elevated temperature modulated the spleen transcriptome response to polyriboinosinic polyribocytidylic acid (pIC, a viral mimic). Herein, we report a complementary microarray study that investigated the impact of the same elevated temperature regime on the Atlantic cod spleen transcriptome response to intraperitoneal (IP) injection of formalin-killed Aeromonas salmonicida (ASAL). Fish were held at two different temperatures (10 °C and 16 °C) prior to immune stimulation and sampled 6 and 24 h post-injection (HPI). In this experiment, we identified 711 and 666 nonredundant ASAL-responsive genes at 6HPI and 24HPI, respectively. These included several known antibacterial genes, including hepcidin, cathelicidin, ferritin heavy subunit, and interleukin 8. However, we only identified 15 differentially expressed genes at 6HPI and 2 at 24HPI (FDR 1%) when comparing ASAL-injected fish held at 10 °C versus 16 °C. In contrast, the same comparisons with pIC-injected fish yielded 290 and 339 differentially expressed genes (FDR 1%) at 6HPI and 24HPI, respectively. These results suggest that moderately elevated temperature has a lesser effect on the Atlantic cod spleen transcriptome response to ASAL (i.e., the antibacterial response) than to pIC (i.e., antiviral response). Thus, the impacts of high temperatures on the cod's immune response may be pathogen dependent.

The other white-nose syndrome transcriptome: Tolerant and susceptible hosts respond differently to the pathogen Pseudogymnoascus destructans.

PubMed

Davy, Christina M; Donaldson, Michael E; Willis, Craig K R; Saville, Barry J; McGuire, Liam P; Mayberry, Heather; Wilcox, Alana; Wibbelt, Gudrun; Misra, Vikram; Bollinger, Trent; Kyle, Christopher J

2017-09-01

Mitigation of emerging infectious diseases that threaten global biodiversity requires an understanding of critical host and pathogen responses to infection. For multihost pathogens where pathogen virulence or host susceptibility is variable, host-pathogen interactions in tolerant species may identify potential avenues for adaptive evolution in recently exposed, susceptible hosts. For example, the fungus Pseudogymnoascus destructans causes white-nose syndrome (WNS) in hibernating bats and is responsible for catastrophic declines in some species in North America, where it was recently introduced. Bats in Europe and Asia, where the pathogen is endemic, are only mildly affected. Different environmental conditions among Nearctic and Palearctic hibernacula have been proposed as an explanation for variable disease outcomes, but this hypothesis has not been experimentally tested. We report the first controlled, experimental investigation of response to P. destructans in a tolerant, European species of bat (the greater mouse-eared bat, Myotis myotis ). We compared body condition, disease outcomes and gene expression in control (sham-exposed) and exposed M. myotis that hibernated under controlled environmental conditions following treatment. Tolerant M. myotis experienced extremely limited fungal growth and did not exhibit symptoms of WNS. However, we detected no differential expression of genes associated with immune response in exposed bats, indicating that immune response does not drive tolerance of P. destructans in late hibernation. Variable responses to P. destructans among bat species cannot be attributed solely to environmental or ecological factors. Instead, our results implicate coevolution with the pathogen, and highlight the dynamic nature of the "white-nose syndrome transcriptome." Interspecific variation in response to exposure by the host (and possibly pathogen) emphasizes the importance of context in studies of the bat-WNS system, and robust characterization of genetic responses to exposure in various hosts and the pathogen should precede any attempts to use particular bat species as generalizable "model hosts."

Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis.

PubMed

de Jong, Emma; Hancock, David G; Wells, Christine; Richmond, Peter; Simmer, Karen; Burgner, David; Strunk, Tobias; Currie, Andrew J

2018-03-13

Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here, we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and postchallenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis-exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis-exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens. © 2018 Australasian Society for Immunology Inc.

Loss of competition in the outside host environment generates outbreaks of environmental opportunist pathogens.

PubMed

Anttila, Jani; Ruokolainen, Lasse; Kaitala, Veijo; Laakso, Jouni

2013-01-01

Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka-Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens.

Host identity matters in the amphibian-Batrachochytrium dendrobatidis system: fine-scale patterns of variation in responses to a multi-host pathogen

Treesearch

Stephanie Gervasi; Carmen Gondhalekar; Deanna H. Olson; Andrew R. Blaustein

2013-01-01

Species composition within ecological assemblages can drive disease dynamics including pathogen invasion, spread, and persistence. In multi-host pathogen systems, interspecific variation in responses to infection creates important context dependency when predicting the outcome of disease. Here, we examine the responses of three sympatric host species to a single fungal...

The NADPH oxidase Cpnox1 is required for full pathogenicity of the ergot fungus Claviceps purpurea.

PubMed

Giesbert, Sabine; Schürg, Timo; Scheele, Sandra; Tudzynski, Paul

2008-05-01

The role of reactive oxygen species (ROS) in interactions between phytopathogenic fungi and their hosts is well established. An oxidative burst mainly caused by superoxide formation by membrane-associated NADPH oxidases is an essential element of plant defence reactions. Apart from primary effects, ROS play a major role as a second messenger in host response. Recently, NADPH oxidase (nox)-encoding genes have been identified in filamentous fungi. Functional analyses have shown that these fungal enzymes are involved in sexual differentiation, and there is growing evidence that they also affect developmental programmes involved in fungus-plant interactions. Here we show that in the biotrophic plant pathogen Claviceps purpurea deletion of the cpnox1 gene, probably encoding an NADPH oxidase, has impact on germination of conidia and pathogenicity: Deltacpnox1 mutants can penetrate the host epidermis, but they are impaired in colonization of the plant ovarian tissue. In the few cases where macroscopic signs of infection (honeydew) appear, they are extremely delayed and fully developed sclerotia have never been observed. C. purpurea Nox1 is important for the interaction with its host, probably by directly affecting pathogenic differentiation of the fungus.

The enemy within: phloem-limited pathogens

USDA-ARS?s Scientific Manuscript database

The growing impact of phloem-limited pathogens on high-value crops has led to a renewed interest in understanding how they cause disease. Although these pathogens cause substantial crop losses, many are poorly characterized. In this review, we present examples of phloem-limited pathogens that includ...

Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity.

PubMed

Odorizzi, Pamela M; Feeney, Margaret E

2016-10-01

Pregnancy-associated malaria, including placental malaria, causes significant morbidity and mortality worldwide. Recently, it has been suggested that in utero exposure of the fetus to malaria antigens may negatively impact the developing immune system and result in tolerance to malaria. Here, we review our current knowledge of fetal immunity to malaria, focusing on the dynamic interactions between maternal malaria infection, placental development, and the fetal immune system. A better understanding of the long-term impact of in utero malaria exposure on the development of natural immunity to malaria, immune responses to other childhood pathogens, and vaccine immunogenicity is urgently needed. This may guide the implementation of novel chemoprevention strategies during pregnancy and facilitate the push toward malaria vaccines. Published by Elsevier Ltd.

Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors.

PubMed

Bliska, James B; Wang, Xiaoying; Viboud, Gloria I; Brodsky, Igor E

2013-10-01

The innate immune system of mammals responds to microbial infection through detection of conserved molecular determinants called 'pathogen-associated molecular patterns' (PAMPs). Pathogens use virulence factors to counteract PAMP-directed responses. The innate immune system can in turn recognize signals generated by virulence factors, allowing for a heightened response to dangerous pathogens. Many Gram-negative bacterial pathogens encode type III secretion systems (T3SSs) that translocate effector proteins, subvert PAMP-directed responses and are critical for infection. A plasmid-encoded T3SS in the human-pathogenic Yersinia species translocates seven effectors into infected host cells. Delivery of effectors by the T3SS requires plasma membrane insertion of two translocators, which are thought to form a channel called a translocon. Studies of the Yersinia T3SS have provided key advances in our understanding of how innate immune responses are generated by perturbations in plasma membrane and other signals that result from translocon insertion. Additionally, studies in this system revealed that effectors function to inhibit innateimmune responses resulting from insertion of translocons into plasma membrane. Here, we review these advances with the goal of providing insight into how a T3SS can activate and inhibit innate immune responses, allowing a virulent pathogen to bypass host defences. © 2013 John Wiley & Sons Ltd.

Effects of Bacillus amyloliquefaciens FZB42 on Lettuce Growth and Health under Pathogen Pressure and Its Impact on the Rhizosphere Bacterial Community

PubMed Central

Rändler, Manuela; Schmid, Michael; Junge, Helmut; Borriss, Rainer; Hartmann, Anton; Grosch, Rita

2013-01-01

The soil-borne pathogen Rhizoctonia solani is responsible for crop losses on a wide range of important crops worldwide. The lack of effective control strategies and the increasing demand for organically grown food has stimulated research on biological control. The aim of the present study was to evaluate the rhizosphere competence of the commercially available inoculant Bacillus amyloliquefaciens FZB42 on lettuce growth and health together with its impact on the indigenous rhizosphere bacterial community in field and pot experiments. Results of both experiments demonstrated that FZB42 is able to effectively colonize the rhizosphere (7.45 to 6.61 Log 10 CFU g−1 root dry mass) within the growth period of lettuce in the field. The disease severity (DS) of bottom rot on lettuce was significantly reduced from severe symptoms with DS category 5 to slight symptom expression with DS category 3 on average through treatment of young plants with FZB42 before and after planting. The 16S rRNA gene based fingerprinting method terminal restriction fragment length polymorphism (T-RFLP) showed that the treatment with FZB42 did not have a major impact on the indigenous rhizosphere bacterial community. However, the bacterial community showed a clear temporal shift. The results also indicated that the pathogen R. solani AG1-IB affects the rhizosphere microbial community after inoculation. Thus, we revealed that the inoculant FZB42 could establish itself successfully in the rhizosphere without showing any durable effect on the rhizosphere bacterial community. PMID:23935892

Yersinia vs. host Immunity: how a pathogen evades or triggers a protective response

PubMed Central

Chung, Lawton K.; Bliska, James B.

2015-01-01

The human pathogenic Yersinia species cause diseases that represent a significant source of morbidity and mortality. Despite this, specific mechanisms underlying Yersinia pathogenesis and protective host responses remain poorly understood. Recent studies have shown that Yersinia disrupt cell death pathways, perturb inflammatory processes and exploit immune cells to promote disease. The ensuing host responses following Yersinia infection include coordination of innate and adaptive immune responses in an attempt to control bacterial replication. Here, we highlight current advances in our understanding of the interactions between the pathogenic yersiniae and host cells, as well as the protective host responses mobilized to counteract these pathogens. Together, these studies enhance our understanding of Yersinia pathogenesis and highlight the ongoing battle between host and microbe. PMID:26638030

Identification, characterisation and expression analysis of natural killer receptor genes in Chlamydia pecorum infected koalas (Phascolarctos cinereus).

PubMed

Morris, Katrina M; Mathew, Marina; Waugh, Courtney; Ujvari, Beata; Timms, Peter; Polkinghorne, Adam; Belov, Katherine

2015-10-15

Koalas (Phascolarctos cinereus), an iconic Australian marsupial, are being heavily impacted by the spread of Chlamydia pecorum, an obligate intracellular bacterial pathogen. Koalas vary in their response to this pathogen, with some showing no symptoms, while others suffer severe symptoms leading to infertility, blindness or death. Little is known about the pathology of this disease and the immune response against it in this host. Studies have demonstrated that natural killer (NK) cells, key components of the innate immune system, are involved in the immune response to chlamydial infections in humans. These cells can directly lyse cells infected by intracellular pathogens and their ability to recognise these infected cells is mediated through NK receptors on their surface. These are encoded in two regions of the genome, the leukocyte receptor complex (LRC) and the natural killer complex (NKC). These two families evolve rapidly and different repertoires of genes, which have evolved by gene duplication, are seen in different species. In this study we aimed to characterise genes belonging to the NK receptor clusters in the koala by searching available koala transcriptomes using a combination of search methods. We developed a qPCR assay to quantify relative expression of four genes, two encoded within the NK receptor cluster (CLEC1B, CLEC4E) and two known to play a role in NK response to Chalmydia in humans (NCR3, PRF1). We found that the NK receptor repertoire of the koala closely resembles that of the Tasmanian devil, with minimal genes in the NKC, but with lineage specific expansions in the LRC. Additional genes important for NK cell activity, NCR3 and PRF1, were also identified and characterised. In a preliminary study to investigate whether these genes are involved in the koala immune response to infection by its chlamydial pathogen, C. pecorum, we investigated the expression of four genes in koalas with active chlamydia infection, those with past infection and those without infection using qPCR. This analysis revealed that one of these four, CLEC4E, may be upregulated in response to chlamydia infection. We have characterised genes of the NKC and LRC in koalas and have discovered evidence that one of these genes may be upregulated in koalas with chlamydia, suggesting that these receptors may play a role in the immune response of koalas to chlamydia infection.

Seed bank survival of an invasive species, but not of two native species, declines with invasion.

PubMed

Orrock, John L; Christopher, Cory C; Dutra, Humberto P

2012-04-01

Soil-borne seed pathogens may play an important role in either hindering or facilitating the spread of invasive exotic plants. We examined whether the invasive shrub Lonicera maackii (Caprifoliaceae) affected fungi-mediated mortality of conspecific and native shrub seeds in a deciduous forest in eastern Missouri. Using a combination of L. maackii removal and fungicide treatments, we found no effect of L. maackii invasion on seed viability of the native Symphoricarpos orbiculatus (Caprifoliaceae) or Cornus drummondii (Cornaceae). In contrast, fungi were significant agents of L. maackii seed mortality in invaded habitats. Losses of L. maackii to soil fungi were also significant in invaded habitats where L. maackii had been removed, although the magnitude of the effect of fungi was lower, suggesting that changes in soil chemistry or microhabitat caused by L. maackii were responsible for affecting fungal seed pathogens. Our work suggests that apparent competition via soil pathogens is not an important factor contributing to impacts of L. maackii on native shrubs. Rather, we found that fungal seed pathogens have density-dependent effects on L. maackii seed survival. Therefore, while fungal pathogens may provide little biotic resistance to early invasion by L. maackii, our study illustrates that more work is needed to understand how changes in fungal pathogens during the course of an invasion contribute to the potential for restoration of invaded systems. More generally, our study suggests that increased rates of fungal pathogen attack may be realized by invasive plants, such as L. maackii, that change the chemical or physical environment of the habitats they invade.

Impact of Nosema ceranae and Nosema apis on individual worker bees of the two host species (Apis cerana and Apis mellifera) and regulation of host immune response.

PubMed

Sinpoo, Chainarong; Paxton, Robert J; Disayathanoowat, Terd; Krongdang, Sasiprapa; Chantawannakul, Panuwan

Nosema apis and Nosema ceranae are obligate intracellular microsporidian parasites infecting midgut epithelial cells of host adult honey bees, originally Apis mellifera and Apis cerana respectively. Each microsporidia cross-infects the other host and both microsporidia nowadays have a worldwide distribution. In this study, cross-infection experiments using both N. apis and N. ceranae in both A. mellifera and A. cerana were carried out to compare pathogen proliferation and impact on hosts, including host immune response. Infection by N. ceranae led to higher spore loads than by N. apis in both host species, and there was greater proliferation of microsporidia in A. mellifera compared to A. cerana. Both N. apis and N. ceranae were pathogenic in both host Apis species. N. ceranae induced subtly, though not significantly, higher mortality than N. apis in both host species, yet survival of A. cerana was no different to that of A. mellifera in response to N. apis or N. ceranae. Infections of both host species with N. apis and N. ceranae caused significant up-regulation of AMP genes and cellular mediated immune genes but did not greatly alter apoptosis-related gene expression. In this study, A. cerana enlisted a higher immune response and displayed lower loads of N. apis and N. ceranae spores than A. mellifera, suggesting it may be better able to defend itself against microsporidia infection. We caution against over-interpretation of our results, though, because differences between host and parasite species in survival were insignificant and because size differences between microsporidia species and between host Apis species may alternatively explain the differential proliferation of N. ceranae in A. mellifera. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Probiotics in the Poultry Industry

PubMed Central

Lutful Kabir, S. M.

2009-01-01

The increase of productivity in the poultry industry has been accompanied by various impacts, including emergence of a large variety of pathogens and bacterial resistance. These impacts are in part due to the indiscriminate use of chemotherapeutic agents as a result of management practices in rearing cycles. This review provides a summary of the use of probiotics for prevention of bacterial diseases in poultry, as well as demonstrating the potential role of probiotics in the growth performance and immune response of poultry, safety and wholesomeness of dressed poultry meat evidencing consumer’s protection, with a critical evaluation of results obtained to date. PMID:20111681

Host-Microbe Interactions in Microgravity: Assessment and Implications

PubMed Central

Foster, Jamie S.; Wheeler, Raymond M.; Pamphile, Regine

2014-01-01

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes. PMID:25370197

Host-microbe interactions in microgravity: assessment and implications.

PubMed

Foster, Jamie S; Wheeler, Raymond M; Pamphile, Regine

2014-05-26

Spaceflight imposes several unique stresses on biological life that together can have a profound impact on the homeostasis between eukaryotes and their associated microbes. One such stressor, microgravity, has been shown to alter host-microbe interactions at the genetic and physiological levels. Recent sequencing of the microbiomes associated with plants and animals have shown that these interactions are essential for maintaining host health through the regulation of several metabolic and immune responses. Disruptions to various environmental parameters or community characteristics may impact the resiliency of the microbiome, thus potentially driving host-microbe associations towards disease. In this review, we discuss our current understanding of host-microbe interactions in microgravity and assess the impact of this unique environmental stress on the normal physiological and genetic responses of both pathogenic and mutualistic associations. As humans move beyond our biosphere and undergo longer duration space flights, it will be essential to more fully understand microbial fitness in microgravity conditions in order to maintain a healthy homeostasis between humans, plants and their respective microbiomes.

Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

PubMed Central

Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P; Sempowski, Gregory D; Frelinger, Jeffrey A

2015-01-01

Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c.DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data. PMID:26029367

Climate warming and disease risks for terrestrial and marine biota

USGS Publications Warehouse

Harvell, C.D.; Mitchell, C.E.; Ward, J.R.; Altizer, S.; Dobson, A.P.; Ostfeld, R.S.; Samuel, M.D.

2002-01-01

Infectious diseases can cause rapid population declines or species extinctions. Many pathogens of terrestrial and marine taxa are sensitive to temperature, rainfall, and humidity, creating synergisms that could affect biodiversity. Climate warming can increase pathogen development and survival rates, disease transmission, and host susceptibility. Although most host-parasite systems are predicted to experience more frequent or severe disease impacts with warming, a subset of pathogens might decline with warming, releasing hosts from disease. Recently, changes in El Niño–Southern Oscillation events have had a detectable influence on marine and terrestrial pathogens, including coral diseases, oyster pathogens, crop pathogens, Rift Valley fever, and human cholera. To improve our ability to predict epidemics in wild populations, it will be necessary to separate the independent and interactive effects of multiple climate drivers on disease impact.

Climate Warming and Disease Risks for Terrestrial and Marine Biota

NASA Astrophysics Data System (ADS)

Harvell, C. Drew; Mitchell, Charles E.; Ward, Jessica R.; Altizer, Sonia; Dobson, Andrew P.; Ostfeld, Richard S.; Samuel, Michael D.

2002-06-01

Infectious diseases can cause rapid population declines or species extinctions. Many pathogens of terrestrial and marine taxa are sensitive to temperature, rainfall, and humidity, creating synergisms that could affect biodiversity. Climate warming can increase pathogen development and survival rates, disease transmission, and host susceptibility. Although most host-parasite systems are predicted to experience more frequent or severe disease impacts with warming, a subset of pathogens might decline with warming, releasing hosts from disease. Recently, changes in El Niño-Southern Oscillation events have had a detectable influence on marine and terrestrial pathogens, including coral diseases, oyster pathogens, crop pathogens, Rift Valley fever, and human cholera. To improve our ability to predict epidemics in wild populations, it will be necessary to separate the independent and interactive effects of multiple climate drivers on disease impact.

Ca2+ conduction by plant cyclic nucleotide gated channels and associated signaling components in pathogen defense signal transduction cascades.

PubMed

Ma, Wei; Berkowitz, Gerald A

2011-05-01

Ca(2+) elevation in the cytosol is an essential early event during pathogen response signaling cascades. However, the specific ion channels involved in Ca(2+) influx into plant cells, and how Ca(2+) signals are initiated and regulate downstream events during pathogen defense responses, are at present unclear. Plant cyclic nucleotide gated ion channels (CNGCs) provide a pathway for Ca(2+) conductance across the plasma membrane (PM) and facilitate cytosolic Ca(2+) elevation in response to pathogen signals. Recent studies indicate that the recognition of pathogens results in cyclic nucleotide production and the activation of CNGCs, which leads to downstream generation of pivotal signaling molecules (such as nitric oxide (NO)). Calmodulins (CaMs) and CaM-like proteins (CMLs) are also involved in this signaling, functioning as Ca(2+) sensors and mediating the synthesis of NO during the plant pathogen response signaling cascade. In this article, these and other pivotal signaling components downstream from the Ca(2+) signal, such as Ca(2+)-dependent protein kinases (CDPKs) and CaM-binding transcription activators (CAMTAs), are discussed in terms of their involvement in the pathogen response signal transduction cascade. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

GLOBAL WARMING AND TRANS-BOUNDARY MOVEMENT OF WATERBORNE MICROBIAL PATHOGENS

EPA Science Inventory

Subtle increases in temperatures can have profound impacts on the prevalence of various waterborne microbial pathogens. Such impacts may be seen in three major areas: 1) fecally-contaminated drinking waters; 2) fresh produce that has been irrigated or processed with contaminated ...

OsMADS26 Negatively Regulates Resistance to Pathogens and Drought Tolerance in Rice1[OPEN

PubMed Central

Khong, Giang Ngan; Richaud, Frédérique; Parizot, Boris; Mai, Chung Duc; Bès, Martine; Bourrié, Isabelle; Meynard, Donaldo; Beeckman, Tom; Selvaraj, Michael Gomez; Manabu, Ishitani; Brugidou, Christophe; Nang Do, Vinh; Guiderdoni, Emmanuel; Morel, Jean-Benoit; Gantet, Pascal

2015-01-01

Functional analyses of MADS-box transcription factors in plants have unraveled their role in major developmental programs (e.g. flowering and floral organ identity) as well as stress-related developmental processes, such as abscission, fruit ripening, and senescence. Overexpression of the rice (Oryza sativa) MADS26 gene in rice has revealed a possible function related to stress response. Here, we show that OsMADS26-down-regulated plants exhibit enhanced resistance against two major rice pathogens: Magnaporthe oryzae and Xanthomonas oryzae. Despite this enhanced resistance to biotic stresses, OsMADS26-down-regulated plants also displayed enhanced tolerance to water deficit. These phenotypes were observed in both controlled and field conditions. Interestingly, alteration of OsMADS26 expression does not have a strong impact on plant development. Gene expression profiling revealed that a majority of genes misregulated in overexpresser and down-regulated OsMADS26 lines compared with control plants are associated to biotic or abiotic stress response. Altogether, our data indicate that OsMADS26 acts as an upstream regulator of stress-associated genes and thereby, a hub to modulate the response to various stresses in the rice plant. PMID:26424158

Insect immunology and hematopoiesis.

PubMed

Hillyer, Julián F

2016-05-01

Insects combat infection by mounting powerful immune responses that are mediated by hemocytes, the fat body, the midgut, the salivary glands and other tissues. Foreign organisms that have entered the body of an insect are recognized by the immune system when pathogen-associated molecular patterns bind host-derived pattern recognition receptors. This, in turn, activates immune signaling pathways that amplify the immune response, induce the production of factors with antimicrobial activity, and activate effector pathways. Among the immune signaling pathways are the Toll, Imd, Jak/Stat, JNK, and insulin pathways. Activation of these and other pathways leads to pathogen killing via phagocytosis, melanization, cellular encapsulation, nodulation, lysis, RNAi-mediated virus destruction, autophagy and apoptosis. This review details these and other aspects of immunity in insects, and discusses how the immune and circulatory systems have co-adapted to combat infection, how hemocyte replication and differentiation takes place (hematopoiesis), how an infection prepares an insect for a subsequent infection (immune priming), how environmental factors such as temperature and the age of the insect impact the immune response, and how social immunity protects entire groups. Finally, this review highlights some underexplored areas in the field of insect immunobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-colonization by Haemophilus influenzae with Streptococcus pneumoniae enhances pneumococcal-specific antibody response in young children.

PubMed

Xu, Qingfu; Pichichero, Michael E

2014-02-03

Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mcat) are common bacterial pathogens of respiratory infections and common commensal microbes in the human nasopharynx (NP). The effect of interactions among theses bacteria during co-colonization of the NP on the host immune response has not been evaluated. The objective of this study was to assess the impact of co-colonization by Hi or Mcat on the systemic antibody response to vaccine protein candidate antigens of Spn and similarly the impact of co-colonization by Spn and Mcat on antibody responses to Hi vaccine protein candidate antigens. Serum samples were collected from healthy children at 6, 9, 15, 18, and 24 months of age when they were colonized with Spn, Hi, Mcat or their combinations. Quantitative ELISA was used to determine serum IgA and IgG against three Spn antigens and three Hi antigens, and as well as whole cells of non-typeable (NT) Spn and Hi. NP colonization by Spn increased serum IgA and IgG titers against Spn antigens PhtD, PcpA and PlyD and whole cells of NTSpn, and co-colonization of Hi or Mcat with Spn resulted in further increases of serum pneumococcal-specific antibody levels. NP colonization by Hi increased serum IgA and IgG titers against Hi antigens P6, Protein D and OMP26 and whole cells of NTHi, but co-colonization of Spn or Mcat with Hi did not result in further increase of serum NTHi-specific antibody levels. Co-colonization of Hi or Mcat with Spn enhances serum antibody response to NTSpn whole cells and Spn vaccine candidate antigens PhtD, PcPA and PlyD1. Co-colonization appears to variably modulate pathogen species-specific host adaptive immune response. Published by Elsevier Ltd.

Interventions for the control of diarrhoeal diseases among young children: improving water supplies and excreta disposal facilities*

PubMed Central

Esrey, S. A.; Feachem, R. G.; Hughes, J. M.

1985-01-01

A theoretical model is proposed that relates the level of ingestion of diarrhoea-causing pathogens to the frequency of diarrhoea in the community. The implications of this model are that, in poor communities with inadequate water supply and excreta disposal, reducing the level of enteric pathogen ingestion by a given amount will have a greater impact on diarrhoea mortality rates than on morbidity rates, a greater impact on the incidence rate of severe diarrhoea than on that of mild diarrhoea, and a greater impact on diarrhoea caused by pathogens having high infectious doses than on diarrhoea caused by pathogens of a low infectious dose. The impact of water supply and sanitation on diarrhoea, related infections, nutritional status, and mortality is analysed by reviewing 67 studies from 28 countries. The median reductions in diarrhoea morbidity rates are 22% from all studies and 27% from a few better-designed studies. All studies of the impact on total mortality rates show a median reduction of 21%, while the few better-designed studies give a median reduction of 30%. Improvements in water quality have less of an impact than improvements in water availability or excreta disposal. PMID:3878742

Intersections between immune responses and morphological regulation in plants.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2010-06-01

Successful plant pathogens have developed strategies to interfere with the defence mechanisms of their host plants through evolution. Conversely, host plants have evolved systems to counteract pathogen attack. Some pathogens induce pathogenic symptoms on plants that include morphological changes in addition to interference with plant growth. Recent studies, based on molecular biology and genetics using Arabidopsis thaliana, have revealed that factors derived from pathogens can modulate host systems and/or host factors that play important roles in the morphological regulation of host plants. Other reports, meanwhile, have shown that factors known to have roles in plant morphology also function in plant immune responses. Evolutionary conservation of these factors and systems implies that host-pathogen interactions and the evolution they drive have yielded tight links between morphological processes and immune responses. In this review, recent findings about these topics are introduced and discussed.

Immune evasion by pathogens of bovine respiratory disease complex.

PubMed

Srikumaran, Subramaniam; Kelling, Clayton L; Ambagala, Aruna

2007-12-01

Bovine respiratory tract disease is a multi-factorial disease complex involving several viruses and bacteria. Viruses that play prominent roles in causing the bovine respiratory disease complex include bovine herpesvirus-1, bovine respiratory syncytial virus, bovine viral diarrhea virus and parinfluenza-3 virus. Bacteria that play prominent roles in this disease complex are Mannheimia haemolytica and Mycoplasma bovis. Other bacteria that infect the bovine respiratory tract of cattle are Histophilus (Haemophilus) somni and Pasteurella multocida. Frequently, severe respiratory tract disease in cattle is associated with concurrent infections of these pathogens. Like other pathogens, the viral and bacterial pathogens of this disease complex have co-evolved with their hosts over millions of years. As much as the hosts have diversified and fine-tuned the components of their immune system, the pathogens have also evolved diverse and sophisticated strategies to evade the host immune responses. These pathogens have developed intricate mechanisms to thwart both the innate and adaptive arms of the immune responses of their hosts. This review presents an overview of the strategies by which the pathogens suppress host immune responses, as well as the strategies by which the pathogens modify themselves or their locations in the host to evade host immune responses. These immune evasion strategies likely contribute to the failure of currently-available vaccines to provide complete protection to cattle against these pathogens.

Visualizing pathogen internalization pathways in fresh tomatoes using MicroCT and confocal laser scanning microscopy

USDA-ARS?s Scientific Manuscript database

Pathogen contamination of fresh produce significantly impacts public health and the produce industry's economic well-being. In tomato fruits, studies have shown that the stem-scar plays an important role in pathogen infiltration. However, the exact mechanisms and pathways for pathogen movement insi...

The Role of TLR2 in Infection and Immunity

PubMed Central

Oliveira-Nascimento, Laura; Massari, Paola; Wetzler, Lee M.

2012-01-01

Toll-like receptors (TLRs) are recognition molecules for multiple pathogens, including bacteria, viruses, fungi, and parasites. TLR2 forms heterodimers with TLR1 and TLR6, which is the initial step in a cascade of events leading to significant innate immune responses, development of adaptive immunity to pathogens and protection from immune sequelae related to infection with these pathogens. This review will discuss the current status of TLR2 mediated immune responses by recognition of pathogen-associated molecular patterns (PAMPS) on these organisms. We will emphasize both canonical and non-canonical responses to TLR2 ligands with emphasis on whether the inflammation induced by these responses contributes to the disease state or to protection from diseases. PMID:22566960

Protein interaction networks at the host-microbe interface in Diaphorina citri, the insect vector of the citrus greening pathogen.

PubMed

Ramsey, J S; Chavez, J D; Johnson, R; Hosseinzadeh, S; Mahoney, J E; Mohr, J P; Robison, F; Zhong, X; Hall, D G; MacCoss, M; Bruce, J; Cilia, M

2017-02-01

The Asian citrus psyllid ( Diaphorina citri) is the insect vector responsible for the worldwide spread of ' Candidatus Liberibacter asiaticus' (CLas), the bacterial pathogen associated with citrus greening disease. Developmental changes in the insect vector impact pathogen transmission, such that D. citri transmission of CLas is more efficient when bacteria are acquired by nymphs when compared with adults. We hypothesize that expression changes in the D. citri immune system and commensal microbiota occur during development and regulate vector competency. In support of this hypothesis, more proteins, with greater fold changes, were differentially expressed in response to CLas in adults when compared with nymphs, including insect proteins involved in bacterial adhesion and immunity. Compared with nymphs, adult insects had a higher titre of CLas and the bacterial endosymbionts Wolbachia, Profftella and Carsonella. All Wolbachia and Profftella proteins differentially expressed between nymphs and adults are upregulated in adults, while most differentially expressed Carsonella proteins are upregulated in nymphs. Discovery of protein interaction networks has broad applicability to the study of host-microbe relationships. Using protein interaction reporter technology, a D. citri haemocyanin protein highly upregulated in response to CLas was found to physically interact with the CLas coenzyme A (CoA) biosynthesis enzyme phosphopantothenoylcysteine synthetase/decarboxylase. CLas pantothenate kinase, which catalyses the rate-limiting step of CoA biosynthesis, was found to interact with a D. citri myosin protein. Two Carsonella enzymes involved in histidine and tryptophan biosynthesis were found to physically interact with D. citri proteins. These co-evolved protein interaction networks at the host-microbe interface are highly specific targets for controlling the insect vector responsible for the spread of citrus greening.

Protein interaction networks at the host–microbe interface in Diaphorina citri, the insect vector of the citrus greening pathogen

PubMed Central

Chavez, J. D.; Johnson, R.; Hosseinzadeh, S.; Mahoney, J. E.; Mohr, J. P.; Robison, F.; Zhong, X.; Hall, D. G.; MacCoss, M.; Bruce, J.; Cilia, M.

2017-01-01

The Asian citrus psyllid (Diaphorina citri) is the insect vector responsible for the worldwide spread of ‘Candidatus Liberibacter asiaticus’ (CLas), the bacterial pathogen associated with citrus greening disease. Developmental changes in the insect vector impact pathogen transmission, such that D. citri transmission of CLas is more efficient when bacteria are acquired by nymphs when compared with adults. We hypothesize that expression changes in the D. citri immune system and commensal microbiota occur during development and regulate vector competency. In support of this hypothesis, more proteins, with greater fold changes, were differentially expressed in response to CLas in adults when compared with nymphs, including insect proteins involved in bacterial adhesion and immunity. Compared with nymphs, adult insects had a higher titre of CLas and the bacterial endosymbionts Wolbachia, Profftella and Carsonella. All Wolbachia and Profftella proteins differentially expressed between nymphs and adults are upregulated in adults, while most differentially expressed Carsonella proteins are upregulated in nymphs. Discovery of protein interaction networks has broad applicability to the study of host–microbe relationships. Using protein interaction reporter technology, a D. citri haemocyanin protein highly upregulated in response to CLas was found to physically interact with the CLas coenzyme A (CoA) biosynthesis enzyme phosphopantothenoylcysteine synthetase/decarboxylase. CLas pantothenate kinase, which catalyses the rate-limiting step of CoA biosynthesis, was found to interact with a D. citri myosin protein. Two Carsonella enzymes involved in histidine and tryptophan biosynthesis were found to physically interact with D. citri proteins. These co-evolved protein interaction networks at the host–microbe interface are highly specific targets for controlling the insect vector responsible for the spread of citrus greening. PMID:28386418

Evolutionary Conservation of Divergent Pro-Inflammatory and Homeostatic Responses in Lamprey Phagocytes

PubMed Central

Havixbeck, Jeffrey J.; Rieger, Aja M.; Wong, Michael E.; Wilkie, Michael P.; Barreda, Daniel R.

2014-01-01

In higher vertebrates, phagocytosis plays a critical role in development and immunity, based on the internalization and removal of apoptotic cells and invading pathogens, respectively. Previous studies describe the effective uptake of these particles by lower vertebrate and invertebrate phagocytes, and identify important molecular players that contribute to this internalization. However, it remains unclear if individual phagocytes mediate internalization processes in these ancient organisms, and how this impacts the balance of pro-inflammatory and homeostatic events within their infection sites. Herein we show that individual phagocytes of the jawless vertebrate Petromyzon marinus (sea lamprey), like those of teleost fish and mice, display the capacity for divergent pro-inflammatory and homeostatic responses following internalization of zymosan and apoptotic cells, respectively. Professional phagocytes (macrophages, monocytes, neutrophils) were the primary contributors to the internalization of pro-inflammatory particles among goldfish (C. auratus) and lamprey (P. marinus) hematopoietic leukocytes. However, goldfish showed a greater ability for zymosan phagocytosis when compared to their jawless counterparts. Coupled to this increase was a significantly lower sensitivity of goldfish phagocytes to homeostatic signals derived from apoptotic cell internalization. Together, this translated into a significantly greater capacity for induction of antimicrobial respiratory burst responses compared to lamprey phagocytes, but also a decreased efficacy in apoptotic cell-driven leukocyte homeostatic mechanisms that attenuate this pro-inflammatory process. Overall, our results show the long-standing evolutionary contribution of intrinsic phagocyte mechanisms for the control of inflammation, and illustrate one effective evolutionary strategy for increased responsiveness against invading pathogens. In addition, they highlight the need for development of complementary regulatory mechanisms of inflammation to ensure continued maintenance of host integrity amidst increasing challenges from invading pathogens. PMID:24465992

Evolutionary conservation of divergent pro-inflammatory and homeostatic responses in Lamprey phagocytes.

PubMed

Havixbeck, Jeffrey J; Rieger, Aja M; Wong, Michael E; Wilkie, Michael P; Barreda, Daniel R

2014-01-01

In higher vertebrates, phagocytosis plays a critical role in development and immunity, based on the internalization and removal of apoptotic cells and invading pathogens, respectively. Previous studies describe the effective uptake of these particles by lower vertebrate and invertebrate phagocytes, and identify important molecular players that contribute to this internalization. However, it remains unclear if individual phagocytes mediate internalization processes in these ancient organisms, and how this impacts the balance of pro-inflammatory and homeostatic events within their infection sites. Herein we show that individual phagocytes of the jawless vertebrate Petromyzon marinus (sea lamprey), like those of teleost fish and mice, display the capacity for divergent pro-inflammatory and homeostatic responses following internalization of zymosan and apoptotic cells, respectively. Professional phagocytes (macrophages, monocytes, neutrophils) were the primary contributors to the internalization of pro-inflammatory particles among goldfish (C. auratus) and lamprey (P. marinus) hematopoietic leukocytes. However, goldfish showed a greater ability for zymosan phagocytosis when compared to their jawless counterparts. Coupled to this increase was a significantly lower sensitivity of goldfish phagocytes to homeostatic signals derived from apoptotic cell internalization. Together, this translated into a significantly greater capacity for induction of antimicrobial respiratory burst responses compared to lamprey phagocytes, but also a decreased efficacy in apoptotic cell-driven leukocyte homeostatic mechanisms that attenuate this pro-inflammatory process. Overall, our results show the long-standing evolutionary contribution of intrinsic phagocyte mechanisms for the control of inflammation, and illustrate one effective evolutionary strategy for increased responsiveness against invading pathogens. In addition, they highlight the need for development of complementary regulatory mechanisms of inflammation to ensure continued maintenance of host integrity amidst increasing challenges from invading pathogens.

The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections.

PubMed

Egli, Adrian; Santer, Deanna M; O'Shea, Daire; Tyrrell, D Lorne; Houghton, Michael

2014-07-01

Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host-pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

Peptidoglycan sensing by octopaminergic neurons modulates Drosophila oviposition

PubMed Central

Kurz, C Leopold; Charroux, Bernard; Chaduli, Delphine; Viallat-Lieutaud, Annelise; Royet, Julien

2017-01-01

As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection, animals can engage in behaviors that lower the impact of the infection. The molecular mechanisms by which microbes impact host behavior are not well understood. We demonstrate that bacterial infection of Drosophila females reduces oviposition and that peptidoglycan, the component that activates Drosophila antibacterial response, is also the elicitor of this behavioral change. We show that peptidoglycan regulates egg-laying rate by activating NF-κB signaling pathway in octopaminergic neurons and that, a dedicated peptidoglycan degrading enzyme acts in these neurons to buffer this behavioral response. This study shows that a unique ligand and signaling cascade are used in immune cells to mount an immune response and in neurons to control fly behavior following infection. This may represent a case of behavioral immunity. DOI: http://dx.doi.org/10.7554/eLife.21937.001 PMID:28264763

Targeted gene flow for conservation.

PubMed

Kelly, Ella; Phillips, Ben L

2016-04-01

Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

Quantifying climate change impacts on runoff of zoonotic pathogens from land

NASA Astrophysics Data System (ADS)

Sterk, Ankie; de Roda Husman, Ana Maria; Stergiadi, Maria; de Nijs, Ton; Schijven, Jack

2013-04-01

Several studies have shown a correlation between rainfall and waterborne disease outbreaks. One of the mechanisms whereby rainfall may cause outbreaks is through an increase in runoff of animal faeces from fields to surface waters. Faeces originating from wildlife, domestic animals or manure-fertilized fields, is considered an important source of zoonotic pathogens to which people may be exposed by water recreation or drinking-water consumption. Climate changes affect runoff because of increasing winter precipitation and more extreme precipitation events, as well as changes in evaporation. Furthermore, drier summers are leading to longer periods of high soil moisture deficits, increasing the hydrophobicity of soil and consequently changing infiltration capacities. A conceptual model is designed to describe the impacts of climate changes on the terrestrial and aquatic ecosystems, which are both directly and indirectly affecting pathogen loads in the environment and subsequent public health risks. One of the major outcomes was the lack of quantitative data and limited qualitative analyses of impacts of climate changes on pathogen runoff. Quantifying the processes by which micro-organisms are transported from fields to waters is important to be able to estimate such impacts to enable targeted implementation of effective intervention measures. A quantitative model using Mathematica software will be developed to estimate concentrations of pathogens originating from overland flow during runoff events. Different input sources will be included by applying different land-use scenarios, including point source faecal pollution from dairy cows and geese and diffuse source pollution by fertilization. Zoonotic pathogens, i.e. Cryptosporidium and Campylobacter, were selected based on transport properties, faecal loads and disease burden. Transport and survival rates of these pathogens are determined including effects of changes in precipitation but also temperature induced changes on die-off. Moreover, besides climate and surface variables, changes in soil or vegetation and adjustments in agricultural policy are considered. Output of this model can be used to assess how expected climate changes could affect pathogen concentrations in surface waters. The long term aim is to include this information in a larger framework, to quantify the impact of climate change on the infection and eventual disease risks due to exposure to water transmitted pathogens.

Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection

PubMed Central

Xu, Zhipeng; Xu, Lei; Li, Wei; Jin, Xin; Song, Xian; Chen, Xiaojun; Zhu, Jifeng; Zhou, Sha; Li, Yong; Zhang, Weiwei; Dong, Xiaoxiao; Yang, Xiaowei; Liu, Feng; Bai, Hui; Chen, Qi; Su, Chuan

2017-01-01

The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction. Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards M2, which subsequently switches T-helper responses from type 1 to type 2. Our study identifies a role for SR-A as an innate PRR in regulating adaptive immune responses. PMID:28695899

Yersinia versus host immunity: how a pathogen evades or triggers a protective response.

PubMed

Chung, Lawton K; Bliska, James B

2016-02-01

The human pathogenic Yersinia species cause diseases that represent a significant source of morbidity and mortality. Despite this, specific mechanisms underlying Yersinia pathogenesis and protective host responses remain poorly understood. Recent studies have shown that Yersinia disrupt cell death pathways, perturb inflammatory processes and exploit immune cells to promote disease. The ensuing host responses following Yersinia infection include coordination of innate and adaptive immune responses in an attempt to control bacterial replication. Here, we highlight current advances in our understanding of the interactions between the pathogenic yersiniae and host cells, as well as the protective host responses mobilized to counteract these pathogens. Together, these studies enhance our understanding of Yersinia pathogenesis and highlight the ongoing battle between host and microbe. Copyright © 2015 Elsevier Ltd. All rights reserved.

The function of small RNAs in plant biotic stress response.

PubMed

Huang, Juan; Yang, Meiling; Zhang, Xiaoming

2016-04-01

Small RNAs (sRNAs) play essential roles in plants upon biotic stress. Plants utilize RNA silencing machinery to facilitate pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity to defend against pathogen attack or to facilitate defense against insect herbivores. Pathogens, on the other hand, are also able to generate effectors and sRNAs to counter the host immune response. The arms race between plants and pathogens/insect herbivores has triggered the evolution of sRNAs, RNA silencing machinery and pathogen effectors. A great number of studies have been performed to investigate the roles of sRNAs in plant defense, bringing in the opportunity to utilize sRNAs in plant protection. Transgenic plants with pathogen-derived resistance ability or transgenerational defense have been generated, which show promising potential as solutions for pathogen/insect herbivore problems in the field. Here we summarize the recent progress on the function of sRNAs in response to biotic stress, mainly in plant-pathogen/insect herbivore interaction, and the application of sRNAs in disease and insect herbivore control. © 2016 Institute of Botany, Chinese Academy of Sciences.

Immunoglobulin gene usage in the human anti-pathogen response.

PubMed

Newkirk, M M; Rioux, J D

1995-09-01

The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

A sex-dependent change in behavioral temperature regulation in African house snakes (Lamprophis fuliginosus) challenged with different pathogens.

PubMed

Ryan, Michael P; Neuman-Lee, Lorin A; Durham, Susan L; Smith, Geoffrey D; French, Susannah S

2018-04-01

Behavioral fever in reptiles is often considered an adaptive response used to eliminate pathogens, yet empirical data showing the wide-spread use of this response is mixed. This behavioral change can be beneficial by enhancing the host's immune response and increasing the animal's chance of survival, but it can also be detrimental in terms of host energetic requirements and enzymatic performance. Thus, we examined whether captive-bred African house snakes (Lamprophis fuliginosus) employed behavioral fever in response to pathogen stimulus. Twenty-one African house snakes were injected separately with three different strains of ultraviolet (UV) light-killed bacteria (Escherichia coli, Staphylococcus aureus, Salmonella enterica). We found an increased variance of hourly cloacal temperatures following exposure to pathogens in male but not female house snakes. We did not, however, find a significant febrile response to pathogen exposure as measured via mean cloacal temperature. This research adds critical information to the field of reptilian physiology as this field remains understudied. Reptilian immune function and its relationship with thermal biology is ever more pertinent as new challenges arise, such as novel pathogens and changing climate. Copyright © 2018 Elsevier Ltd. All rights reserved.

Shared and organism-specific host responses to childhood diarrheal diseases revealed by whole blood transcript profiling.

PubMed

DeBerg, Hannah A; Zaidi, Mussaret B; Altman, Matthew C; Khaenam, Prasong; Gersuk, Vivian H; Campos, Freddy D; Perez-Martinez, Iza; Meza-Segura, Mario; Chaussabel, Damien; Banchereau, Jacques; Estrada-Garcia, Teresa; Linsley, Peter S

2018-01-01

Globally, diarrheal diseases are a leading cause of death in children under five and disproportionately affect children in developing countries. Children who contract diarrheal diseases are rarely screened to identify the etiologic agent due to time and cost considerations associated with pathogen-specific screening and hence pathogen-directed therapy is uncommon. The development of biomarkers to rapidly identify underlying pathogens could improve treatment options and clinical outcomes in childhood diarrheal diseases. Here, we perform RNA sequencing on blood samples collected from children evaluated in an emergency room setting with diarrheal disease where the pathogen(s) present are known. We determine host response gene signatures specific to Salmonella, Shigella and rotavirus, but not E. coli, infections that distinguish them from each other and from healthy controls. Specifically, we observed differential expression of genes related to chemokine receptors or inflammasome signaling in Shigella cases, such as CCR3, CXCR8, and NLRC4, and interferon response genes, such as IFI44 and OASL, in rotavirus cases. Our findings add insight into the host peripheral immune response to these pathogens, and suggest strategies and limitations for the use host response transcript signatures for diagnosing the etiologic agent of childhood diarrheal diseases.

A cellular backline: specialization of host membranes for defence.

PubMed

Faulkner, Christine

2015-03-01

In plant-pathogen interactions, the host plasma membrane serves as a defence front for pathogens that invade from the extracellular environment. As such, the lipid bilayer acts as a scaffold that targets and delivers defence responses to the site of attack. During pathogen infection, numerous changes in plasma membrane composition, organization, and structure occur. There is increasing evidence that this facilitates the execution of a variety of responses, highlighting the regulatory role membranes play in cellular responses. Membrane microdomains such as lipid rafts are hypothesized to create signalling platforms for receptor signalling in response to pathogen perception and for callose synthesis. Further, the genesis of pathogen-associated structures such as papillae and the extra-haustorial membrane necessitates polarization of membranes and membrane trafficking pathways. Unlocking the mechanisms by which this occurs will enable greater understanding of how targeted defences, some of which result in resistance, are executed. This review will survey some of the changes that occur in host membranes during pathogen attack and how these are associated with the generation of defence responses. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Review of the Interactions between Wheat and Wheat Pathogens: Zymoseptoria tritici, Fusarium spp. and Parastagonospora nodorum

PubMed Central

Duba, Adrian; Goriewa-Duba, Klaudia; Wachowska, Urszula

2018-01-01

Zymoseptoria tritici is a hemibiotrophic pathogen which causes Septoria leaf blotch in wheat. The pathogenesis of the disease consists of a biotrophic phase and a necrotrophic phase. The pathogen infects the host plant by suppressing its immune response in the first stage of infection. Hemibiotrophic pathogens of the genus Fusarium cause Fusarium head blight, and the necrotrophic Parastagonospora nodorum is responsible for Septoria nodorum blotch in wheat. Cell wall-degrading enzymes in plants promote infections by necrotrophic and hemibiotrophic pathogens, and trichothecenes, secondary fungal metabolites, facilitate infections caused by fungi of the genus Fusarium. There are no sources of complete resistance to the above pathogens in wheat. Defense mechanisms in wheat are controlled by many genes encoding resistance traits. In the wheat genome, the characteristic features of loci responsible for resistance to pathogenic infections indicate that at least several dozen genes encode resistance to pathogens. The molecular interactions between wheat and Z. tritici, P. nodorum and Fusarium spp. pathogens have been insufficiently investigated. Most studies focus on the mechanisms by which the hemibiotrophic Z. tritici suppresses immune responses in plants and the role of mycotoxins and effector proteins in infections caused by P. nodorum and Fusarium spp. fungi. Trichothecene glycosylation and effector proteins, which are involved in defense responses in wheat, have been described at the molecular level. Recent advances in molecular biology have produced interesting findings which should be further elucidated in studies of molecular interactions between wheat and fungal pathogens. The Clustered Regularly-Interspaced Short Palindromic Repeats/ CRISPR associated (CRISPR/Cas) system can be used to introduce targeted mutations into the wheat genome and confer resistance to selected fungal diseases. Host-induced gene silencing and spray-induced gene silencing are also useful tools for analyzing wheat–pathogens interactions which can be used to develop new strategies for controlling fungal diseases. PMID:29642627

Import risk assessment incorporating a dose-response model: introduction of highly pathogenic porcine reproductive and respiratory syndrome into Australia via illegally imported raw pork.

PubMed

Brookes, V J; Hernández-Jover, M; Holyoake, P; Ward, M P

2014-03-01

Highly pathogenic porcine reproductive and respiratory syndrome (PRRS) has spread through parts of south-east Asia, posing a risk to Australia. The objective of this study was to assess the probability of infection of a feral or domestic pig in Australia with highly pathogenic PRRS following ingestion of illegally imported raw pork. A conservative scenario was considered in which 500 g of raw pork was imported from the Philippines into Australia without being detected by border security, then discarded from a household and potentially accessed by a pig. Monte Carlo simulation of a two-dimensional, stochastic model was used to estimate the probability of entry and exposure, and the probability of infection was assessed by incorporating a virus-decay and mechanistic dose-response model. Results indicated that the probability of infection of a feral pig after ingestion of raw meat was higher than the probability of infection of a domestic pig. Sensitivity analysis was used to assess the influence of input parameters on model output probability estimates, and extension of the virus-decay and dose-response model was used to explore the impact of different temperatures and time from slaughter to ingestion of the meat, different weights of meat, and the level of viraemia at slaughter on the infectivity of meat. Parameters with the highest influence on the model output were the level of viraemia of a pig prior to slaughter and the probability of access by a feral pig to food-waste discarded on property surrounding a household. Extension of the decay and dose-response model showed that small pieces of meat (10 g) from a highly pathogenic PRRS viraemic pig could contain enough virus to have a high probability of infection of a pig, and that routes to Australia by sea or air from all highly pathogenic PRRS virus endemic countries were of interest dependent on the temperature of the raw meat during transport. This study highlighted the importance of mitigation strategies such as disposal of food-waste from international traffic as quarantine waste, and the need for further research into the probability of access to food-waste on properties by feral pigs. Copyright © 2014 Elsevier B.V. All rights reserved.

DETECTING AND MITIGATING THE ENVIRONMENTAL IMPACT OF FECAL PATHOGENS ORIGINATING FROM CONFINED ANIMAL FEEDING OPERATIONS: REVIEW

EPA Science Inventory

This report presents a review of literature regarding the potential impact of fecal pathogens originating from animal agriculture in the United States. Livestock production and dairy operations continue their trend toward larger and more concentrated facilities. These operations ...

Global Warming and Trans-Boundary Movement of Waterborne Microbial Pathogens - Book Chapter

EPA Science Inventory

Subtle increases in temperature can have profound impacts on the prevalence of various waterborne microbial pathogens. Such impacts may be seen in three major areas, 1) fecally contaminated drinking water, 2) fresh produce that has been irrigated or processed with contaminated wa...

A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4

PubMed Central

Alsina, L; Israelsson, E; Altman, MC; Dang, KK; Ghandil, P; Israel, L; von Bernuth, H; Baldwin, N; Qin, H; Jin, Z; Banchereau, R; Anguiano, E; Ionan, A; Abel, L; Puel, A; Picard, C; Pascual, V; Casanova, JL; Chaussabel, D

2014-01-01

Loss of function in the kinase IRAK-4 or the adapter MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. Yet patients with loss of function mutations are surprisingly only susceptible to a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients’ blood to Toll-like receptor and interleukin-1 receptor agonists, and whole pathogens. Responses to purified agonists were globally abolished but variable residual responses were present following exposure to whole pathogens. Further dissection of the latter responses identified a narrow repertoire of immune transcriptional programs affected by loss of MyD88 or IRAK-4 function. This work introduces the use of a systems approach for the global assessment of innate immune responses, and the characterization of human primary immunodeficiencies. PMID:25344726

Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency of Anaplasma marginale

USDA-ARS?s Scientific Manuscript database

The relative fitness of arthropod-borne pathogens within the vector can be a major determinant of pathogen prevalence within the mammalian host population. Strains of the tick-borne rickettsia Anaplasma marginale differ markedly in transmission efficiency with consequent impact on pathogen strain st...

Pathogen Loading From Canada Geese Faeces in Freshwater: Potential Risks to Human Health Through Recreational Water Exposure.

PubMed

Gorham, T J; Lee, J

2016-05-01

Canada geese (Branta canadensis) faeces have been shown to contain pathogenic protozoa and bacteria in numerous studies over the past 15 years. Further, increases in both the Canada geese populations and their ideal habitat requirements in the United States (US) translate to a greater presence of these human pathogens in public areas, such as recreational freshwater beaches. Combining these factors, the potential health risk posed by Canada geese faeces at freshwater beaches presents an emerging public health issue that warrants further study. Here, literature concerning human pathogens in Canada geese faeces is reviewed and the potential impacts these pathogens may have on human health are discussed. Pathogens of potential concern include Campylobacter jejuni, Salmonella Typhimurium, Listeria monocytogenes, Helicobacter canadensis, Arcobacter spp., Enterohemorragic Escherichia coli pathogenic strains, Chlamydia psitacci, Cryptosporidium parvum and Giardia lamblia. Scenarios presenting potential exposure to pathogens eluted from faeces include bathers swimming in lakes, children playing with wet and dry sand impacted by geese droppings and other common recreational activities associated with public beaches. Recent recreational water-associated disease outbreaks in the US support the plausibility for some of these pathogens, including Cryptosporidium spp. and C. jejuni, to cause human illness in this setting. In view of these findings and the uncertainties associated with the real health risk posed by Canada geese faecal pathogens to users of freshwater lakes, it is recommended that beach managers use microbial source tracking and conduct a quantitative microbial risk assessment to analyse the local impact of Canada geese on microbial water quality during their decision-making process in beach and watershed management. © 2015 Blackwell Verlag GmbH.

Differential apple transcriptomic responses to penicillium expansum (pathogen) and penicillium digitatum (non-host pathogen) infection

USDA-ARS?s Scientific Manuscript database

Penicillium expansum is the causal agent of blue mould of pome fruits and is responsible for important economical losses during postharvest handling in all producing countries. Although control of this pathogen can be achieved by using chemical fungicides, the appearance of resistant strains and in...

Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection.

PubMed

Estep, Ryan D; Messaoudi, Ilhem; O'Connor, Megan A; Li, Helen; Sprague, Jerald; Barron, Alexander; Engelmann, Flora; Yen, Bonnie; Powers, Michael F; Jones, John M; Robinson, Bridget A; Orzechowska, Beata U; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Wilk, Jennifer; Axthelm, Michael K; Wong, Scott W

2011-09-01

Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola virus, the causative agent of smallpox. Human MPXV infection results in a disease that is similar to smallpox and can also be fatal. Two clades of MPXV have been identified, with viruses of the central African clade displaying more pathogenic properties than those within the west African clade. The monkeypox inhibitor of complement enzymes (MOPICE), which is not expressed by viruses of the west African clade, has been hypothesized to be a main virulence factor responsible for increased pathogenic properties of central African strains of MPXV. To gain a better understanding of the role of MOPICE during MPXV-mediated disease, we compared the host adaptive immune response and disease severity following intrabronchial infection with MPXV-Zaire (n = 4), or a recombinant MPXV-Zaire (n = 4) lacking expression of MOPICE in rhesus macaques (RM). Data presented here demonstrate that infection of RM with MPXV leads to significant viral replication in the peripheral blood and lungs and results in the induction of a robust and sustained adaptive immune response against the virus. More importantly, we show that the loss of MOPICE expression results in enhanced viral replication in vivo, as well as a dampened adaptive immune response against MPXV. Taken together, these findings suggest that MOPICE modulates the anti-MPXV immune response and that this protein is not the sole virulence factor of the central African clade of MPXV.

Crude oil impairs immune function and increases susceptibility to pathogenic bacteria in southern flounder

PubMed Central

Bayha, Keith M.; Ortell, Natalie; Ryan, Caitlin N.; Griffitt, Kimberly J.; Krasnec, Michelle; Sena, Johnny; Ramaraj, Thiruvarangan; Takeshita, Ryan; Mayer, Gregory D.; Schilkey, Faye; Griffitt, Robert J.

2017-01-01

Exposure to crude oil or its individual constituents can have detrimental impacts on fish species, including impairment of the immune response. Increased observations of skin lesions in northern Gulf of Mexico fish during the 2010 Deepwater Horizon oil spill indicated the possibility of oil-induced immunocompromisation resulting in bacterial or viral infection. This study used a full factorial design of oil exposure and bacterial challenge to examine how oil exposure impairs southern flounder (Paralichthys lethostigma) immune function and increases susceptibility to the bacteria Vibrio anguillarum, a causative agent of vibriosis. Fish exposed to oil prior to bacterial challenge exhibited 94.4% mortality within 48 hours of bacterial exposure. Flounder challenged with V. anguillarum without prior oil exposure had <10% mortality. Exposure resulted in taxonomically distinct gill and intestine bacterial communities. Mortality strongly correlated with V. anguillarum levels, where it comprised a significantly higher percentage of the microbiome in Oil/Pathogen challenged fish and was nearly non-existent in the No Oil/Pathogen challenged fish bacterial community. Elevated V. anguillarum levels were a direct result of oil exposure-induced immunosuppression. Oil-exposure reduced expression of immunoglobulin M, the major systemic fish antibody, and resulted in an overall downregulation in transcriptome response, particularly in genes related to immune function, response to stimulus and hemostasis. Ultimately, sediment-borne oil exposure impairs immune function, leading to increased incidences of bacterial infections. This type of sediment-borne exposure may result in long-term marine ecosystem effects, as oil-bound sediment in the northern Gulf of Mexico will likely remain a contamination source for years to come. PMID:28464028

Impacts of fever on locust life-history traits: costs or benefits?

PubMed Central

Elliot, Sam L; Horton, Charlotte M; Blanford, Simon; Thomas, Matthew B

2005-01-01

Fever, like other mechanisms for defence against pathogens, may have positive and negative consequences for host fitness. In ectotherms, fever can be attained through modified behavioural thermoregulation. Here we examine potential costs of behavioural fever by holding adult, gregarious desert locusts at elevated temperatures simulating a range of fever intensities. We found no effect of fever temperatures on primary fitness correlates of survival and fecundity. However, flight capacity and mate competition were reduced, although there was no relation between time spent at fever temperatures and magnitude of the response. While these effects could indicate a direct cost of fever, they are also consistent with a shift towards the solitaria phase state that, in a field context, could be considered an adaptive life-history response to limit the impact of disease. These conflicting interpretations highlight the importance of considering complex defence mechanisms and trade-offs in an appropriate ecological context. PMID:17148161

Simulating the recent impacts of multiple biotic disturbances on forest carbon cycling across the United States.

PubMed

Kautz, Markus; Anthoni, Peter; Meddens, Arjan J H; Pugh, Thomas A M; Arneth, Almut

2018-05-01

Biotic disturbances (BDs, for example, insects, pathogens, and wildlife herbivory) substantially affect boreal and temperate forest ecosystems globally. However, accurate impact assessments comprising larger spatial scales are lacking to date although these are critically needed given the expected disturbance intensification under a warming climate. Hence, our quantitative knowledge on current and future BD impacts, for example, on forest carbon (C) cycling, is strongly limited. We extended a dynamic global vegetation model to simulate ecosystem response to prescribed tree mortality and defoliation due to multiple biotic agents across United States forests during the period 1997-2015, and quantified the BD-induced vegetation C loss, that is, C fluxes from live vegetation to dead organic matter pools. Annual disturbance fractions separated by BD type (tree mortality and defoliation) and agent (bark beetles, defoliator insects, other insects, pathogens, and other biotic agents) were calculated at 0.5° resolution from aerial-surveyed data and applied within the model. Simulated BD-induced C fluxes totaled 251.6 Mt C (annual mean: 13.2 Mt C year -1 , SD ±7.3 Mt C year -1 between years) across the study domain, to which tree mortality contributed 95% and defoliation 5%. Among BD agents, bark beetles caused most C fluxes (61%), and total insect-induced C fluxes were about five times larger compared to non-insect agents, for example, pathogens and wildlife. Our findings further demonstrate that BD-induced C cycle impacts (i) displayed high spatio-temporal variability, (ii) were dominated by different agents across BD types and regions, and (iii) were comparable in magnitude to fire-induced impacts. This study provides the first ecosystem model-based assessment of BD-induced impacts on forest C cycling at the continental scale and going beyond single agent-host systems, thus allowing for comparisons across regions, BD types, and agents. Ultimately, a perspective on the potential and limitations of a more process-based incorporation of multiple BDs in ecosystem models is offered. © 2017 John Wiley & Sons Ltd.

Post-translational derepression of invertase activity in source leaves via down-regulation of invertase inhibitor expression is part of the plant defense response.

PubMed

Bonfig, Katharina B; Gabler, Andrea; Simon, Uwe K; Luschin-Ebengreuth, Nora; Hatz, Martina; Berger, Susanne; Muhammad, Naseem; Zeier, Jürgen; Sinha, Alok K; Roitsch, Thomas

2010-11-01

There is increasing evidence that pathogens do not only elicit direct defense responses, but also cause pronounced changes in primary carbohydrate metabolism. Cell-wall-bound invertases belong to the key regulators of carbohydrate partitioning and source-sink relations. Whereas studies have focused so far only on the transcriptional induction of invertase genes in response to pathogen infection, the role of post-translational regulation of invertase activity has been neglected and was the focus of the present study. Expression analyses revealed that the high mRNA level of one out of three proteinaceous invertase inhibitors in source leaves of Arabidopsis thaliana is strongly repressed upon infection by a virulent strain of Pseudomonas syringae pv. tomato DC3000. This repression is paralleled by a decrease in invertase inhibitor activity. The physiological role of this regulatory mechanism is revealed by the finding that in situ invertase activity was detectable only upon infection by P. syringae. In contrast, a high invertase activity could be measured in vitro in crude and cell wall extracts prepared from both infected and non-infected leaves. The discrepancy between the in situ and in vitro invertase activity of control leaves and the high in situ invertase activity in infected leaves can be explained by the pathogen-dependent repression of invertase inhibitor expression and a concomitant reduction in invertase inhibitor activity. The functional importance of the release of invertase from post-translational inhibition for the defense response was substantiated by the application of the competitive chemical invertase inhibitor acarbose. Post-translational inhibition of extracellular invertase activity by infiltration of acarbose in leaves was shown to increase the susceptibility to P. syringae. The impact of invertase inhibition on spatial and temporal dynamics of the repression of photosynthesis and promotion of bacterial growth during pathogen infection supports a role for extracellular invertase in plant defense. The acarbose-mediated increase in susceptibility was also detectable in sid2 and cpr6 mutants and resulted in slightly elevated levels of salicylic acid, demonstrating that the effect is independent of the salicylic acid-regulated defense pathway. These findings provide an explanation for high extractable invertase activity found in source leaves that is kept inhibited in situ by post-translational interaction between invertase and the invertase inhibitor proteins. Upon pathogen infection, the invertase activity is released by repression of invertase inhibitor expression, thus linking the local induction of sink strength to the plant defense response.

Impact of hormonal crosstalk on plant resistance and fitness under multi-attacker conditions

PubMed Central

Vos, Irene A.; Moritz, Liselotte; Pieterse, Corné M. J.; Van Wees, Saskia C. M.

2015-01-01

The hormone salicylic acid (SA) generally induces plant defenses against biotrophic pathogens. Jasmonic acid (JA) and its oxylipin derivatives together with ethylene (ET) are generally important hormonal regulators of induced plant defenses against necrotrophic pathogens, whereas JAs together with abscisic acid (ABA) are implicated in induced plant defenses against herbivorous insects. Hormonal crosstalk between the different plant defense pathways has often been hypothesized to be a cost-saving strategy that has evolved as a means of the plant to reduce allocation costs by repression of unnecessary defenses, thereby minimizing trade-offs between plant defense and growth. However, proof for this hypothesis has not been demonstrated yet. In this study the impact of hormonal crosstalk on disease resistance and fitness of Arabidopsis thaliana when under multi-species attack was investigated. Induction of SA- or JA/ABA-dependent defense responses by the biotrophic pathogen Hyaloperonospora arabidopsidis or the herbivorous insect Pieris rapae, respectively, was shown to reduce the level of induced JA/ET-dependent defense against subsequent infection with the necrotrophic pathogen Botrytis cinerea. However, despite the enhanced susceptibility to this second attacker, no additional long-term negative effects were observed on plant fitness when plants had been challenged by multiple attackers. Similarly, when plants were grown in dense competition stands to enlarge fitness effects of induced defenses, treatment with a combination of SA and MeJA did not cause additional negative effects on plant fitness in comparison to the single MeJA treatment. Together, these data support the notion that hormonal crosstalk in plants during multi-attacker interactions allows plants to prioritize their defenses, while limiting the fitness costs associated with induction of defenses. PMID:26347758

A Meta-Analysis of the Impact of Anaerobic Soil Disinfestation on Pest Suppression and Yield of Horticultural Crops

PubMed Central

Shrestha, Utsala; Augé, Robert M.; Butler, David M.

2016-01-01

Anaerobic soil disinfestation (ASD) is a proven but relatively new strategy to control soil borne pests of horticultural crops through anaerobic decomposition of organic soil amendments. The ASD technique has primarily been used to control soil borne pathogens; however, this technique has also shown potential to control plant parasitic nematodes and weeds. ASD can utilize a broad range of carbon (C) amendments and optimization may improve efficacy across environments. In this context, a meta-analysis using a random-effects model was conducted to determine effect sizes of the ASD effect on soil borne pathogens (533 studies), plant parasitic nematodes (91 studies), and weeds (88 studies) compared with unamended controls. Yield response to ASD was evaluated (123 studies) compared to unamended and fumigated controls. We also examined moderator variables for environmental conditions and amendments to explore the impact of these moderators on ASD effectiveness on pests and yield. Across all pathogen types with the exception of Sclerotinia spp., ASD studies show suppression of bacterial, oomycete and fungal pathogens (59 to 94%). Pathogen suppression was effective under all environmental conditions (50 to 94%) and amendment types (53 to 97%), except when amendments were applied at rates less than 0.3 kg m-2. The ASD effect ranged from 15 to 56% for nematode suppression and 32 to 81% for weed suppression, but these differences were not significant. Significant nematode moderators included study type, soil type, sampling depth, incubation period, and use of mixed amendments. Weed suppression due to ASD showed significant heterogeneity for all environmental conditions, confirming that these studies do not share a common effect size. Total crop yield was not reduced by ASD when compared to a fumigant control and yield was significantly higher (30%) compared to an unamended control, suggesting ASD as a feasible option to maintain yield without chemical soil fumigants. We conclude ASD is effective against soil borne pathogens and while not conclusive due to a limited number of studies, we expect the same for nematodes and weeds given observed effect sizes. Findings should assist researchers in exploring ASD efficacy in particular environmental conditions and allow for development of standard treatment protocols. PMID:27617017

Evaluating the success of an emergency response medical information system.

PubMed

Petter, Stacie; Fruhling, Ann

2011-07-01

STATPack™ is an information system used to aid in the diagnosis of pathogens in hospitals and state public health laboratories. STATPack™ is used as a communication and telemedicine diagnosis tool during emergencies. This paper explores the success of this emergency response medical information system (ERMIS) using a well-known framework of information systems success developed by DeLone and McLean. Using an online survey, the entire population of STATPack™ users evaluated the success of the information system by considering system quality, information quality, system use, intention to use, user satisfaction, individual impact, and organizational impact. The results indicate that the overall quality of this ERMIS (i.e., system quality, information quality, and service quality) has a positive impact on both user satisfaction and intention to use the system. However, given the nature of ERMIS, overall quality does not necessarily predict use of the system. Moreover, the user's satisfaction with the information system positively affected the intention to use the system. User satisfaction, intention to use, and system use had a positive influence on the system's impact on the individual. Finally, the organizational impacts of the system were positively influenced by use of the system and the system's individual impact on the user. The results of the study demonstrate how to evaluate the success of an ERMIS as well as introduce potential changes in how one applies the DeLone and McLean success model in an emergency response medical information system context. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Regulation of Stomatal Immunity by Interdependent Functions of a Pathogen-Responsive MPK3/MPK6 Cascade and Abscisic Acid

PubMed Central

Zhang, Lawrence; Sun, Tiefeng

2017-01-01

Activation of mitogen-activated protein kinases (MAPKs) is one of the earliest responses after plants sense an invading pathogen. Here, we show that MPK3 and MPK6, two Arabidopsis thaliana pathogen-responsive MAPKs, and their upstream MAPK kinases, MKK4 and MKK5, are essential to both stomatal and apoplastic immunity. Loss of function of MPK3 and MPK6, or their upstream MKK4 and MKK5, abolishes pathogen/microbe-associated molecular pattern- and pathogen-induced stomatal closure. Gain-of-function activation of MPK3/MPK6 induces stomatal closure independently of abscisic acid (ABA) biosynthesis and signaling. In contrast, exogenously applied organic acids such as malate or citrate are able to reverse the stomatal closure induced by MPK3/MPK6 activation. Gene expression analysis and in situ enzyme activity staining revealed that malate metabolism increases in guard cells after activation of MPK3/MPK6 or inoculation of pathogen. In addition, pathogen-induced malate metabolism requires functional MKK4/MKK5 and MPK3/MPK6. We propose that the pathogen-responsive MPK3/MPK6 cascade and ABA are two essential signaling pathways that control, respectively, the organic acid metabolism and ion channels, two main branches of osmotic regulation in guard cells that function interdependently to control stomatal opening/closure. PMID:28254778

Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?

PubMed Central

Aronoff, David M.

2012-01-01

Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach “worked” in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings. PMID:22665954

Crop Fertilization Impacts Epidemics and Optimal Latent Period of Biotrophic Fungal Pathogens.

PubMed

Précigout, Pierre-Antoine; Claessen, David; Robert, Corinne

2017-10-01

Crop pathogens are known to rapidly adapt to agricultural practices. Although cultivar resistance breakdown and resistance to pesticides have been broadly studied, little is known about the adaptation of crop pathogens to fertilization regimes and no epidemiological model has addressed that question. However, this is a critical issue for developing sustainable low-input agriculture. In this article, we use a model of life history evolution of biotrophic wheat fungal pathogens in order to understand how they could adapt to changes in fertilization practices. We focus on a single pathogen life history trait, the latent period, which directly determines the amount of resources allocated to growth and reproduction along with the speed of canopy colonization. We implemented three fertilization scenarios, corresponding to major effects of increased nitrogen fertilization on crops: (i) increase in nutrient concentration in leaves, (ii) increase of leaf lifespan, and (iii) increase of leaf number (tillering) and size that leads to a bigger canopy size. For every scenario, we used two different fitness measures to identify putative evolutionary responses of latent period to changes in fertilization level. We observed that annual spore production increases with fertilization, because it results in more resources available to the pathogens. Thus, diminishing the use of fertilizers could reduce biotrophic fungal epidemics. We found a positive relationship between the optimal latent period and fertilization when maximizing total spore production over an entire season. In contrast, we found a negative relationship between the optimal latent period and fertilization when maximizing the within-season exponential growth rate of the pathogen. These contrasting results were consistent over the three tested fertilization scenarios. They suggest that between-strain diversity in the latent period, as has been observed in the field, may be due to diversifying selection in different cultural environments.

Molecular profiling of the Phytophthora plurivora secretome: a step towards understanding the cross-talk between plant pathogenic oomycetes and their hosts.

PubMed

Severino, Valeria; Farina, Annarita; Fleischmann, Frank; Dalio, Ronaldo J D; Di Maro, Antimo; Scognamiglio, Monica; Fiorentino, Antonio; Parente, Augusto; Osswald, Wolfgang; Chambery, Angela

2014-01-01

The understanding of molecular mechanisms underlying host-pathogen interactions in plant diseases is of crucial importance to gain insights on different virulence strategies of pathogens and unravel their role in plant immunity. Among plant pathogens, Phytophthora species are eliciting a growing interest for their considerable economical and environmental impact. Plant infection by Phytophthora phytopathogens is a complex process coordinated by a plethora of extracellular signals secreted by both host plants and pathogens. The characterization of the repertoire of effectors secreted by oomycetes has become an active area of research for deciphering molecular mechanisms responsible for host plants colonization and infection. Putative secreted proteins by Phytophthora species have been catalogued by applying high-throughput genome-based strategies and bioinformatic approaches. However, a comprehensive analysis of the effective secretome profile of Phytophthora is still lacking. Here, we report the first large-scale profiling of P. plurivora secretome using a shotgun LC-MS/MS strategy. To gain insight on the molecular signals underlying the cross-talk between plant pathogenic oomycetes and their host plants, we also investigate the quantitative changes of secreted protein following interaction of P. plurivora with the root exudate of Fagus sylvatica which is highly susceptible to the root pathogen. We show that besides known effectors, the expression and/or secretion levels of cell-wall-degrading enzymes were altered following the interaction with the host plant root exudate. In addition, a characterization of the F. sylvatica root exudate was performed by NMR and amino acid analysis, allowing the identification of the main released low-molecular weight components, including organic acids and free amino acids. This study provides important insights for deciphering the extracellular network involved in the highly susceptible P. plurivora-F. sylvatica interaction.

Short term memory of Caenorhabditis elegans against bacterial pathogens involves CREB transcription factor.

PubMed

Prithika, Udayakumar; Vikneswari, Ramaraj; Balamurugan, Krishnaswamy

2017-04-01

One of the key issues pertaining to the control of memory is to respond to a consistently changing environment or microbial niche present in it. Human cyclic AMP response element binding protein (CREB) transcription factor which plays a crucial role in memory has a homolog in C. elegans, crh-1. crh-1 appears to influence memory processes to certain extent by habituation of the host to a particular environment. The discrimination between the pathogen and a non-pathogen is essential for C. elegans in a microbial niche which determines its survival. Training the nematodes in the presence of a virulent pathogen (S. aureus) and an opportunistic pathogen (P. mirabilis) separately exhibits a different behavioural paradigm. This appears to be dependent on the CREB transcription factor. Here we show that C. elegans homolog crh-1 helps in memory response for a short term against the interacting pathogens. Following conditioning of the nematodes to S. aureus and P. mirabilis, the wild type nematodes exhibited a positive response towards the respective pathogens which diminished slowly after 2h. By contrast, the crh-1 deficient nematodes had a defective memory post conditioning. The molecular data reinforces the importance of crh-1 gene in retaining the memory of nematode. Our results also suggest that involvement of neurotransmitters play a crucial role in modulating the memory of the nematode with the assistance of CREB. Therefore, we elucidate that CREB is responsible for the short term memory response in C. elegans against bacterial pathogens. Copyright © 2016 Elsevier GmbH. All rights reserved.

Applications of nanomaterials as vaccine adjuvants

PubMed Central

Zhu, Motao; Wang, Rongfu; Nie, Guangjun

2014-01-01

Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

Virulence of oomycete pathogens from Phragmites australis-invaded and noninvaded soils to seedlings of wetland plant species

PubMed Central

Crocker, Ellen V; Karp, Mary Ann; Nelson, Eric B

2015-01-01

Soil pathogens affect plant community structure and function through negative plant–soil feedbacks that may contribute to the invasiveness of non-native plant species. Our understanding of these pathogen-induced soil feedbacks has relied largely on observations of the collective impact of the soil biota on plant populations, with few observations of accompanying changes in populations of specific soil pathogens and their impacts on invasive and noninvasive species. As a result, the roles of specific soil pathogens in plant invasions remain unknown. In this study, we examine the diversity and virulence of soil oomycete pathogens in freshwater wetland soils invaded by non-native Phragmites australis (European common reed) to better understand the potential for soil pathogen communities to impact a range of native and non-native species and influence invasiveness. We isolated oomycetes from four sites over a 2-year period, collecting nearly 500 isolates belonging to 36 different species. These sites were dominated by species of Pythium, many of which decreased seedling survival of a range of native and invasive plants. Despite any clear host specialization, many of the Pythium species were differentially virulent to the native and non-native plant species tested. Isolates from invaded and noninvaded soils were equally virulent to given individual plant species, and no apparent differences in susceptibility were observed between the collective groups of native and non-native plant species. PMID:26078850

Influence of oak woodland composition and structure on infection by Phytophthora ramorum

Treesearch

Nathan Rank; Hall Cushman; Brian Anacker; David Rizzo; Ross Meentemeyer

2008-01-01

Introduced plant pathogens have major ecological impacts in many parts of the world. While the spread of pathogens can be strongly mediated by the composition and structure of local host plant communities, little is known about effects of plant community structure on invasion dynamics of introduced pathogens. The progress of infection by the invasive pathogen ...

Transcriptome Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

PubMed Central

Kolliopoulou, Anna; Van Nieuwerburgh, Filip; Stravopodis, Dimitrios J.; Deforce, Dieter; Swevers, Luc; Smagghe, Guy

2015-01-01

Many insects can be persistently infected with viruses but do not show any obvious adverse effects with respect to physiology, development or reproduction. Here, Bombyx mori strain Daizo, persistently infected with cytoplasmic polyhedrosis virus (BmCPV), was used to study the host’s transcriptional response after pathogenic infection with the same virus in midgut tissue of larvae persistently and pathogenically infected as 2nd and 4th instars. Next generation sequencing revealed that from 13,769 expressed genes, 167 were upregulated and 141 downregulated in both larval instars following pathogenic infection. Several genes that could possibly be involved in B. mori immune response against BmCPV or that may be induced by the virus in order to increase infectivity were identified, whereas classification of differentially expressed transcripts (confirmed by qRT-PCR) resulted in gene categories related to physical barriers, immune responses, proteolytic / metabolic enzymes, heat-shock proteins, hormonal signaling and uncharacterized proteins. Comparison of our data with the available literature (pathogenic infection of persistently vs. non-persistently infected larvae) unveiled various similarities of response in both cases, which suggests that pre-existing persistent infection does not affect in a major way the transcriptome response against pathogenic infection. To investigate the possible host’s RNAi response against BmCPV challenge, the differential expression of RNAi-related genes and the accumulation of viral small RNAs (vsRNAs) were studied. During pathogenic infection, siRNA-like traces like the 2-fold up-regulation of the core RNAi genes Ago-2 and Dcr-2 as well as a peak of 20 nt small RNAs were observed. Interestingly, vsRNAs of the same size were detected at lower rates in persistently infected larvae. Collectively, our data provide an initial assessment of the relative significance of persistent infection of silkworm larvae on the host response following pathogenic infection with CPV, while they also highlight the relative importance of RNAi as an antiviral mechanism. PMID:25816294

Streptococcus pyogenes Infection and the Human Proteome with a Special Focus on the Immunoglobulin G-cleaving Enzyme IdeS.

PubMed

Karlsson, Christofer A Q; Järnum, Sofia; Winstedt, Lena; Kjellman, Christian; Björck, Lars; Linder, Adam; Malmström, Johan A

2018-06-01

Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a combined mass spectrometry-based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes , with a particular focus on bacterial cleavage of IgG in vivo In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG. S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Ustilago maydis populations tracked maize through domestication and cultivation in the Americas

PubMed Central

Munkacsi, Andrew B; Stoxen, Sam; May, Georgiana

2008-01-01

The domestication of crops and the development of agricultural societies not only brought about major changes in human interactions with the environment but also in plants' interactions with the diseases that challenge them. We evaluated the impact of the domestication of maize from teosinte and the widespread cultivation of maize on the historical demography of Ustilago maydis, a fungal pathogen of maize. To determine the evolutionary response of the pathogen's populations, we obtained multilocus genotypes for 1088 U. maydis diploid individuals from two teosinte subspecies in Mexico and from maize in Mexico and throughout the Americas. Results identified five major U. maydis populations: two in Mexico; two in South America; and one in the United States. The two populations in Mexico diverged from the other populations at times comparable to those for the domestication of maize at 6000–10 000 years before present. Maize domestication and agriculture enforced sweeping changes in U. maydis populations such that the standing variation in extant pathogen populations reflects evolution only since the time of the crop's domestication. PMID:18252671

Water quality impacts from on-site waste disposal systems to coastal areas through groundwater discharge

NASA Astrophysics Data System (ADS)

Harris, P. J.

1995-12-01

This report summarizes research studies linking on-site waste disposal systems (OSDS) to pathogen and nutrient concentrations in groundwater with the potential to impact coastal embayments. Few studies connect OSDS to coastal water quality. Most studies examined pathogen and nutrient impacts to groundwater and omitted estimations of contaminants discharged to surface water. The majority of studies focused on nitrogen, with little information on pathogens and even less on phosphorus. Nitrogen discharged from OSDS poses the greatest threat to water quality. Vertical distance of septic tank infiltration system from the water table, septic system design, and siting remain the key components in minimizing potential impacts from OSDS for control of both pathogens and nutrients. The most comprehensive information connecting nutrient contributions from OSDS to surface water quality was the study conducted on Buttermilk Bay in Massachusetts where 74% of nitrogen to the bay was attributed to onsite disposal systems. In conclusion, further studies on the viability and transport of pathogens and nutrients through the groundwater aquifer and across the groundwater/surface-water interface are needed. Additional research on the importance of septic system design on the availability of contaminants to groundwater as well as the minimum distance between the septic system and water table necessary to protect groundwater are also indicated.

Modelling the impact of co-circulating low pathogenic avian influenza viruses on epidemics of highly pathogenic avian influenza in poultry.

PubMed

Nickbakhsh, Sema; Hall, Matthew D; Dorigatti, Ilaria; Lycett, Samantha J; Mulatti, Paolo; Monne, Isabella; Fusaro, Alice; Woolhouse, Mark E J; Rambaut, Andrew; Kao, Rowland R

2016-12-01

It is well known that highly pathogenic avian influenza (HPAI) viruses emerge through mutation of precursor low pathogenic avian influenza (LPAI) viruses in domestic poultry populations. The potential for immunological cross-protection between these pathogenic variants is recognised but the epidemiological impact during co-circulation is not well understood. Here we use mathematical models to investigate whether altered flock infection parameters consequent to primary LPAI infections can impact on the spread of HPAI at the population level. First we used mechanistic models reflecting the co-circulatory dynamics of LPAI and HPAI within a single commercial poultry flock. We found that primary infections with LPAI led to HPAI prevalence being maximised under a scenario of high but partial cross-protection. We then tested the population impact in spatially-explicit simulations motivated by a major avian influenza A(H7N1) epidemic that afflicted the Italian poultry industry in 1999-2001. We found that partial cross-protection can lead to a prolongation of HPAI epidemic duration. Our findings have implications for the control of HPAI in poultry particularly for settings in which LPAI and HPAI frequently co-circulate. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Molecular effects of resistance elicitors from biological origin and their potential for crop protection

PubMed Central

Wiesel, Lea; Newton, Adrian C.; Elliott, Ian; Booty, David; Gilroy, Eleanor M.; Birch, Paul R. J.; Hein, Ingo

2014-01-01

Plants contain a sophisticated innate immune network to prevent pathogenic microbes from gaining access to nutrients and from colonizing internal structures. The first layer of inducible response is governed by the plant following the perception of microbe- or modified plant-derived molecules. As the perception of these molecules results in a plant response that can provide efficient resistance toward non-adapted pathogens they can also be described as “defense elicitors.” In compatible plant/microbe interactions, adapted microorganisms have means to avoid or disable this resistance response and promote virulence. However, this requires a detailed spatial and temporal response from the invading pathogens. In agricultural practice, treating plants with isolated defense elicitors in the absence of pathogens can promote plant resistance by uncoupling defense activation from the effects of pathogen virulence determinants. The plant responses to plant, bacterial, oomycete, or fungal-derived elicitors are not, in all cases, universal and need elucidating prior to the application in agriculture. This review provides an overview of currently known elicitors of biological rather than synthetic origin and places their activity into a molecular context. PMID:25484886

Molecular effects of resistance elicitors from biological origin and their potential for crop protection.

PubMed

Wiesel, Lea; Newton, Adrian C; Elliott, Ian; Booty, David; Gilroy, Eleanor M; Birch, Paul R J; Hein, Ingo

2014-01-01

Plants contain a sophisticated innate immune network to prevent pathogenic microbes from gaining access to nutrients and from colonizing internal structures. The first layer of inducible response is governed by the plant following the perception of microbe- or modified plant-derived molecules. As the perception of these molecules results in a plant response that can provide efficient resistance toward non-adapted pathogens they can also be described as "defense elicitors." In compatible plant/microbe interactions, adapted microorganisms have means to avoid or disable this resistance response and promote virulence. However, this requires a detailed spatial and temporal response from the invading pathogens. In agricultural practice, treating plants with isolated defense elicitors in the absence of pathogens can promote plant resistance by uncoupling defense activation from the effects of pathogen virulence determinants. The plant responses to plant, bacterial, oomycete, or fungal-derived elicitors are not, in all cases, universal and need elucidating prior to the application in agriculture. This review provides an overview of currently known elicitors of biological rather than synthetic origin and places their activity into a molecular context.

Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens.

PubMed

Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M

2010-08-01

Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling, and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens--notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)--also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across Kingdoms.

Linking ecology and epidemiology to understand predictors of multi-host responses to an emerging pathogen, the amphibian chytrid fungus

Treesearch

Stephanie S. Gervasi; Patrick R. Stephens; Jessica Hua; Catherine L. Searle; Gisselle Yang Xie; Jenny Urbina; Deanna H. Olson; Betsy A. Bancroft; Virginia Weis; John I. Hammond; Rick A. Relyea; Andrew R. Blaustein; Stefan Lötters

2017-01-01

Variation in host responses to pathogens can have cascading effects on populations and communities when some individuals or groups of individuals display disproportionate vulnerability to infection or differ in their competence to transmit infection. The fungal pathogen, Batrachochytrium dendrobatidis (Bd) has been detected in almost 700 different...

Pathogen-induced elicitin production in transgenic tobacco generates a hypersensitive response and nonspecific disease resistance.

PubMed Central

Keller, H; Pamboukdjian, N; Ponchet, M; Poupet, A; Delon, R; Verrier, J L; Roby, D; Ricci, P

1999-01-01

The rapid and effective activation of disease resistance responses is essential for plant defense against pathogen attack. These responses are initiated when pathogen-derived molecules (elicitors) are recognized by the host. We have developed a strategy for creating novel disease resistance traits whereby transgenic plants respond to infection by a virulent pathogen with the production of an elicitor. To this end, we generated transgenic tobacco plants harboring a fusion between the pathogen-inducible tobacco hsr 203J gene promoter and a Phytophthora cryptogea gene encoding the highly active elicitor cryptogein. Under noninduced conditions, the transgene was silent, and no cryptogein could be detected in the transgenic plants. In contrast, infection by the virulent fungus P. parasitica var nicotianae stimulated cryptogein production that coincided with the fast induction of several defense genes at and around the infection sites. Induced elicitor production resulted in a localized necrosis that resembled a P. cryptogea-induced hypersensitive response and that restricted further growth of the pathogen. The transgenic plants displayed enhanced resistance to fungal pathogens that were unrelated to Phytophthora species, such as Thielaviopsis basicola, Erysiphe cichoracearum, and Botrytis cinerea. Thus, broad-spectrum disease resistance of a plant can be generated without the constitutive synthesis of a transgene product. PMID:9927640

Fueling the caries process: carbohydrate metabolism and gene regulation by Streptococcus mutans

PubMed Central

Moye, Zachary D.; Zeng, Lin; Burne, Robert A.

2014-01-01

The nature of the oral cavity and host behaviors has mandated that the oral microbiota evolve mechanisms for coping with environmental fluctuations, especially changes in the type and availability of carbohydrates. In the case of human dental caries, the presence of excess carbohydrates is often responsible for altering the local environment to be more favorable for species associated with the initiation and progression of disease, including Streptococcus mutans. Some of the earliest endeavors to understand how cariogenic species respond to environmental perturbations were carried out using chemostat cultivation, which provides fine control over culture conditions and bacterial behaviors. The development of genome-scale methodologies has allowed for the combination of sophisticated cultivation technologies with genome-level analysis to more thoroughly probe how bacterial pathogens respond to environmental stimuli. Recent investigations in S. mutans and other closely related streptococci have begun to reveal that carbohydrate metabolism can drastically impact pathogenic potential and highlight the important influence that nutrient acquisition has on the success of pathogens; inside and outside of the oral cavity. Collectively, research into pathogenic streptococci, which have evolved in close association with the human host, has begun to unveil the essential nature of careful orchestration of carbohydrate acquisition and catabolism to allow the organisms to persist and, when conditions allow, initiate or worsen disease. PMID:25317251

Comparative analysis of European bat lyssavirus 1 pathogenicity in the mouse model.

PubMed

Eggerbauer, Elisa; Pfaff, Florian; Finke, Stefan; Höper, Dirk; Beer, Martin; Mettenleiter, Thomas C; Nolden, Tobias; Teifke, Jens-Peter; Müller, Thomas; Freuling, Conrad M

2017-06-01

European bat lyssavirus 1 is responsible for most bat rabies cases in Europe. Although EBLV-1 isolates display a high degree of sequence identity, different sublineages exist. In individual isolates various insertions and deletions have been identified, with unknown impact on viral replication and pathogenicity. In order to assess whether different genetic features of EBLV-1 isolates correlate with phenotypic changes, different EBLV-1 variants were compared for pathogenicity in the mouse model. Groups of three mice were infected intracranially (i.c.) with 102 TCID50/ml and groups of six mice were infected intramuscularly (i.m.) with 105 TCID50/ml and 102 TCID50/ml as well as intranasally (i.n.) with 102 TCID50/ml. Significant differences in survival following i.m. inoculation with low doses as well as i.n. inoculation were observed. Also, striking variations in incubation periods following i.c. inoculation and i.m. inoculation with high doses were seen. Hereby, the clinical picture differed between general symptoms, spasms and aggressiveness depending on the inoculation route. Immunohistochemistry of mouse brains showed that the virus distribution in the brain depended on the inoculation route. In conclusion, different EBLV-1 isolates differ in pathogenicity indicating variation which is not reflected in studies of single isolates.

Comparative analysis of European bat lyssavirus 1 pathogenicity in the mouse model

PubMed Central

Eggerbauer, Elisa; Pfaff, Florian; Finke, Stefan; Höper, Dirk; Beer, Martin; Mettenleiter, Thomas C.; Nolden, Tobias; Teifke, Jens-Peter; Müller, Thomas

2017-01-01

European bat lyssavirus 1 is responsible for most bat rabies cases in Europe. Although EBLV-1 isolates display a high degree of sequence identity, different sublineages exist. In individual isolates various insertions and deletions have been identified, with unknown impact on viral replication and pathogenicity. In order to assess whether different genetic features of EBLV-1 isolates correlate with phenotypic changes, different EBLV-1 variants were compared for pathogenicity in the mouse model. Groups of three mice were infected intracranially (i.c.) with 102 TCID50/ml and groups of six mice were infected intramuscularly (i.m.) with 105 TCID50/ml and 102 TCID50/ml as well as intranasally (i.n.) with 102 TCID50/ml. Significant differences in survival following i.m. inoculation with low doses as well as i.n. inoculation were observed. Also, striking variations in incubation periods following i.c. inoculation and i.m. inoculation with high doses were seen. Hereby, the clinical picture differed between general symptoms, spasms and aggressiveness depending on the inoculation route. Immunohistochemistry of mouse brains showed that the virus distribution in the brain depended on the inoculation route. In conclusion, different EBLV-1 isolates differ in pathogenicity indicating variation which is not reflected in studies of single isolates. PMID:28628617

Systematic characterization of the peroxidase gene family provides new insights into fungal pathogenicity in Magnaporthe oryzae

PubMed Central

Mir, Albely Afifa; Park, Sook-Young; Sadat, Md. Abu; Kim, Seongbeom; Choi, Jaeyoung; Jeon, Junhyun; Lee, Yong-Hwan

2015-01-01

Fungal pathogens have evolved antioxidant defense against reactive oxygen species produced as a part of host innate immunity. Recent studies proposed peroxidases as components of antioxidant defense system. However, the role of fungal peroxidases during interaction with host plants has not been explored at the genomic level. Here, we systematically identified peroxidase genes and analyzed their impact on fungal pathogenesis in a model plant pathogenic fungus, Magnaporthe oryzae. Phylogeny reconstruction placed 27 putative peroxidase genes into 15 clades. Expression profiles showed that majority of them are responsive to in planta condition and in vitro H2O2. Our analysis of individual deletion mutants for seven selected genes including MoPRX1 revealed that these genes contribute to fungal development and/or pathogenesis. We identified significant and positive correlations among sensitivity to H2O2, peroxidase activity and fungal pathogenicity. In-depth analysis of MoPRX1 demonstrated that it is a functional ortholog of thioredoxin peroxidase in Saccharomyces cerevisiae and is required for detoxification of the oxidative burst within host cells. Transcriptional profiling of other peroxidases in ΔMoprx1 suggested interwoven nature of the peroxidase-mediated antioxidant defense system. The results from this study provide insight into the infection strategy built on evolutionarily conserved peroxidases in the rice blast fungus. PMID:26134974

Giardia: a pathogen or commensal for children in high prevalence settings?

PubMed Central

Bartelt, Luther A.

2016-01-01

Purpose of review Giardia is a common intestinal parasite worldwide, and infection can be associated with clear and sometimes persistent symptomatology. However, in children in high prevalence settings, it is not associated with or is perhaps even protective against acute diarrhea, and the association with long-term outcomes has been difficult to discern. Recent findings Recent studies have made progress in helping us disentangle this apparent paradox. First, prospective, well-characterized cohort studies have added to the data on the association between Giardia and diarrhea in these settings and have further characterized associations between Giardia infection and nutrition, gut function, and growth. Second, animal models have further characterized the host response to Giardia and helped elucidate mechanisms by which Giardia could impair child development. Finally, new work has shed light on the heterogeneity of human Giardia strains, which may both explain discrepant findings in the literature and help guide higher-resolution analyses of this pathogen in the future. Summary The true clinical impact of endemic pediatric giardiasis remains unclear, but recent prospective studies have confirmed a high prevalence of persistent, subclinical Giardia infections and associated growth shortfalls. Integrating how nutritional, microbial, metabolic, and pathogen-strain variables influence these outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite. PMID:27479025

Giardia: a pathogen or commensal for children in high-prevalence settings?

PubMed

Bartelt, Luther A; Platts-Mills, James A

2016-10-01

Giardia is a common intestinal parasite worldwide, and infection can be associated with clear and sometimes persistent symptomatology. However, in children in high-prevalence settings, it is not associated with or is perhaps even protective against acute diarrhea, and the association with long-term outcomes has been difficult to discern. Recent studies have made progress in helping us disentangle this apparent paradox. First, prospective, well-characterized cohort studies have added to the data on the association between Giardia and diarrhea in these settings and have further characterized associations between Giardia infection and nutrition, gut function, and growth. Second, animal models have further characterized the host response to Giardia and helped elucidate mechanisms by which Giardia could impair child development. Finally, new work has shed light on the heterogeneity of human Giardia strains, which may both explain discrepant findings in the literature and help guide higher-resolution analyses of this pathogen in the future. The true clinical impact of endemic pediatric giardiasis remains unclear, but recent prospective studies have confirmed a high prevalence of persistent, subclinical Giardia infections and associated growth shortfalls. Integrating how nutritional, microbial, metabolic, and pathogen-strain variables influence these outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite.

Improved Phytophthora resistance in commercial chickpea (Cicer arietinum) varieties negatively impacts symbiotic gene signalling and symbiotic potential in some varieties.

PubMed

Plett, Jonathan M; Plett, Krista L; Bithell, Sean L; Mitchell, Chris; Moore, Kevin; Powell, Jeff R; Anderson, Ian C

2016-08-01

Breeding disease-resistant varieties is one of the most effective and economical means to combat soilborne diseases in pulse crops. Commonalities between pathogenic and mutualistic microbe colonization strategies, however, raises the concern that reduced susceptibility to pathogens may simultaneously reduce colonization by beneficial microbes. We investigate here the degree of overlap in the transcriptional response of the Phytophthora medicaginis susceptible chickpea variety 'Sonali' to the early colonization stages of either Phytophthora, rhizobial bacteria or arbuscular mycorrhizal fungi. From a total of 6476 genes differentially expressed in Sonali roots during colonization by any of the microbes tested, 10.2% were regulated in a similar manner regardless of whether it was the pathogenic oomycete or a mutualistic microbe colonizing the roots. Of these genes, 49.7% were oppositely regulated under the same conditions in the moderately Phytophthora resistant chickpea variety 'PBA HatTrick'. Chickpea varieties with improved resistance to Phytophthora also displayed lower colonization by rhizobial bacteria and mycorrhizal fungi leading to an increased reliance on N and P from soil. Together, our results suggest that marker-based breeding in crops such as chickpea should be further investigated such that plant disease resistance can be tailored to a specific pathogen without affecting mutualistic plant:microbe interactions. © 2016 John Wiley & Sons Ltd.

A time series analysis of the relationship of ambient temperature and common bacterial enteric infections in two Canadian provinces

NASA Astrophysics Data System (ADS)

Fleury, Manon; Charron, Dominique F.; Holt, John D.; Allen, O. Brian; Maarouf, Abdel R.

2006-07-01

The incidence of enteric infections in the Canadian population varies seasonally, and may be expected to be change in response to global climate changes. To better understand any potential impact of warmer temperature on enteric infections in Canada, we investigated the relationship between ambient temperature and weekly reports of confirmed cases of three pathogens in Canada: Salmonella, pathogenic Escherichia coli and Campylobacter, between 1992 and 2000 in two Canadian provinces. We used generalized linear models (GLMs) and generalized additive models (GAMs) to estimate the effect of seasonal adjustments on the estimated models. We found a strong non-linear association between ambient temperature and the occurrence of all three enteric pathogens in Alberta, Canada, and of Campylobacter in Newfoundland-Labrador. Threshold models were used to quantify the relationship of disease and temperature with thresholds chosen from 0 to -10°C depending on the pathogen modeled. For Alberta, the log relative risk of Salmonella weekly case counts increased by 1.2%, Campylobacter weekly case counts increased by 2.2%, and E. coli weekly case counts increased by 6.0% for every degree increase in weekly mean temperature. For Newfoundland-Labrador the log relative risk increased by 4.5% for Campylobacter for every degree increase in weekly mean temperature.

Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants.

PubMed

Larsen, Jeppe Madura; Brix, Susanne; Thysen, Anna Hammerich; Birch, Sune; Rasmussen, Morten Arendt; Bisgaard, Hans

2014-04-01

Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonization of neonatal airways with the pathogenic bacterial strains Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy. We aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years. The Copenhagen Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response was assessed based on the pattern of cytokines produced and T-cell activation. The immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17 (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition. Children with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic bacteria colonizing the airways in early life might lead to chronic airway inflammation and childhood asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Bacteremia due to ESKAPE pathogens: An emerging problem in cancer patients.

PubMed

El-Mahallawy, Hadir A; Hassan, Safaa Shawky; El-Wakil, Mohamed; Moneer, Manar M

2016-09-01

In recent years, a few of the antibiotic-resistant bacteria, known as ESKAPE pathogens, have been found responsible for serious infections. We investigated the risk factors, and impact of ESKAPE pathogens on course of blood stream infections (BSIs) in cancer patients in comparison to coagulase negative Staphylococci (CoNS). The data of patients with ESKAPE positive blood cultures at National Cancer Institute, Cairo University were analyzed. Identification and antimicrobial susceptibility of isolates were done using Microscan Walk Away 96. In a 6month period, ESKAPE pathogens were isolated from non-duplicate blood cultures in 81 episodes of 72 cases of pediatric cancer patients, while CoNS were isolated from 135 blood cultures of 116 patients. The ESKAPE pathogens isolated were Enterobacter spp., methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci in 12%, 23%, 37%, 10%, 9%, and 9% of episodes, respectively. Health-care acquired infections constituted 75% of ESKAPE infections. Duration of episodes and overall mortality were significantly higher in ESKAPE BSIs when compared to CoNS (14.5±7.6 versus 09.9±6.9), and (26% versus 4%); respectively, p value <0.001. ESKAPE pathogens were significantly associated with higher rates of morbidity and mortality indicating the need for improving the means of prevention of these types of infections within health care premises. Microbiology laboratories have a role in defining more dangerous infections and rapid diagnostics are required in the era of resistance. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Decreased waterborne pathogenic bacteria in an urban aquifer related to intense shallow geothermal exploitation.

PubMed

García-Gil, Alejandro; Gasco-Cavero, Samanta; Garrido, Eduardo; Mejías, Miguel; Epting, Jannis; Navarro-Elipe, Mercedes; Alejandre, Carmen; Sevilla-Alcaine, Elena

2018-08-15

The implications of intensive use of shallow geothermal energy resources in shallow urban aquifers are still not known for waterborne pathogens relevant to human health. Firstly, we hypothesized that waterborne enteric pathogens would be relatively increased in heated groundwater plumes. To prove this, microbiological sampling of 31 piezometers covering the domain of an urban groundwater body affected by microbiological contamination and energetically exploited by 70 groundwater heat pump systems was performed. Mean differences of pathogenic bacteria contents between impacted and non-impacted monitoring points were assessed with a two-tailed independent Student's t-test or Mann-Whitney U and correlation coefficients were also calculated. Surprisingly, the results obtained revealed a significant and generalized decrease in waterborne pathogen contents in thermally impacted piezometers compared to that of non-impacted piezometers. This decrease is hypothesized to be caused by a heat shock to bacteria within the heat exchangers. The statistically significant negative correlations obtained between waterborne pathogen counts and temperature could be explained by the spatial distribution of the bacteria, finding that bacteria start to recover with increasing distance from the injection point. Also, different behavior groups fitting exponential regression models were found for the bacteria species studied, justified by the different presence and influence of several aquifer parameters and major, minor and trace elements studied, as well as the coexistence with other bacteria species. The results obtained from this work reinforce the concept of shallow geothermal resources as a clean energy source, as they could also provide the basis to control the pathogenic bacteria contents in groundwater bodies. Copyright © 2018 Elsevier B.V. All rights reserved.

Insights From Natural Host-Parasite Interactions: The Drosophila Model

PubMed Central

Keebaugh, Erin S.; Schlenke, Todd A.

2013-01-01

Immune responses against opportunistic pathogens have been extensively studied in Drosophila, leading to a detailed map of the genetics behind innate immunity networks including the Toll, Imd, Jak-Stat, and JNK pathways. However, immune mechanisms of other organisms, particularly plants, have primarily been investigated using natural pathogens. It was the use of natural pathogens in plant research that revealed the plant R/Avr system, a specialized immune response derived from antagonistic coevolution between plant immune proteins and their natural pathogens’ virulence proteins. Thus, we recommend that researchers begin to use natural Drosophila pathogens to identify novel immune mechanisms that may have arisen through antagonistic coevolution with common natural pathogens. In this review, we address the benefits of using natural pathogens in research, describe the known natural pathogens of Drosophila, and discuss exciting prospects for future research on select natural pathogens of Drosophila. PMID:23764256

Antigenic Variation and Immune Escape in the MTBC

PubMed Central

2017-01-01

Microbes that infect other organisms encounter host immune responses, and must overcome or evade innate and adaptive immune responses to successfully establish infection. Highly successful microbial pathogens, including M. tuberculosis, are able to evade adaptive immune responses (mediated by antibodies and/or T lymphocytes) and thereby establish long-term chronic infection. One mechanism that diverse pathogens use to evade adaptive immunity is antigenic variation, in which structural variants emerge that alter recognition by established immune responses and allow those pathogens to persist and/or to infect previously-immune hosts. Despite the wide use of antigenic variation by diverse pathogens, this mechanism appears to be infrequent in M. tuberculosis, as indicated by findings that known and predicted human T cell epitopes in this organism are highly conserved, although there are exceptions. These findings have implications for diagnostic tests that are based on measuring host immune responses, and for vaccine design and development. PMID:29116635

Chemokine-mediated immune responses in the female genital tract mucosa.

PubMed

Deruaz, Maud; Luster, Andrew D

2015-04-01

The genital tract mucosa is the site where sexually transmitted infections gain entry to the host. The immune response at this site is thus critical to provide innate protection against pathogens that are seen for the very first time as well as provide long-term pathogen-specific immunity, which would be required for an effective vaccine against sexually transmitted infection. A finely regulated immune response is therefore required to provide an effective barrier against pathogens without compromising the capacity of the genital tract to allow for successful conception and fetal development. We review recent developments in our understanding of the immune response in the female genital tract to infectious pathogens, using herpes simplex virus-2, human immunodeficiency virus-1 and Chlamydia trachomatis as examples, with a particular focus on the role of chemokines in orchestrating immune cell migration necessary to achieve effective innate and adaptive immune responses in the female genital tract.

Skin-transmitted pathogens and the heebie jeebies: evidence for a subclass of disgust stimuli that evoke a qualitatively unique emotional response.

PubMed

Blake, Khandis R; Yih, Jennifer; Zhao, Kun; Sung, Billy; Harmon-Jones, Cindy

2017-09-01

Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response "the heebie jeebies". In Study 1, coding of 76 participants' experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin-crawling sensations and an urge to protect the skin. In Experiment 2,350 participants' responses to skin-transmitted pathogen, fear-inducing, and disgust-inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli (178 participants). Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct.

The Role of Stress and Stress Adaptations in Determining the Fate of the Bacterial Pathogen Listeria monocytogenes in the Food Chain.

PubMed

NicAogáin, Kerrie; O'Byrne, Conor P

2016-01-01

The foodborne pathogen Listeria monocytogenes is a highly adaptable organism that can persist in a wide range of environmental and food-related niches. The consumption of contaminated ready-to-eat foods can cause infections, termed listeriosis, in vulnerable humans, particularly those with weakened immune systems. Although these infections are comparatively rare they are associated with high mortality rates and therefore this pathogen has a significant impact on food safety. L. monocytogenes can adapt to and survive a wide range of stress conditions including low pH, low water activity, and low temperature, which makes it problematic for food producers who rely on these stresses for preservation. Stress tolerance in L. monocytogenes can be explained partially by the presence of the general stress response (GSR), a transcriptional response under the control of the alternative sigma factor sigma B (σ B ) that reconfigures gene transcription to provide homeostatic and protective functions to cope with the stress. Within the host σ B also plays a key role in surviving the harsh conditions found in the gastrointestinal tract. As the infection progresses beyond the GI tract L. monocytogenes uses an intracellular infectious cycle to propagate, spread and remain protected from the host's humoral immunity. Many of the virulence genes that facilitate this infectious cycle are under the control of a master transcriptional regulator called PrfA. In this review we consider the environmental reservoirs that enable L. monocytogenes to gain access to the food chain and discuss the stresses that the pathogen must overcome to survive and grow in these environments. The overlap that exists between stress tolerance and virulence is described. We review the principal measures that are used to control the pathogen and point to exciting new approaches that might provide improved means of control in the future.

The Role of Stress and Stress Adaptations in Determining the Fate of the Bacterial Pathogen Listeria monocytogenes in the Food Chain

PubMed Central

NicAogáin, Kerrie; O’Byrne, Conor P.

2016-01-01

The foodborne pathogen Listeria monocytogenes is a highly adaptable organism that can persist in a wide range of environmental and food-related niches. The consumption of contaminated ready-to-eat foods can cause infections, termed listeriosis, in vulnerable humans, particularly those with weakened immune systems. Although these infections are comparatively rare they are associated with high mortality rates and therefore this pathogen has a significant impact on food safety. L. monocytogenes can adapt to and survive a wide range of stress conditions including low pH, low water activity, and low temperature, which makes it problematic for food producers who rely on these stresses for preservation. Stress tolerance in L. monocytogenes can be explained partially by the presence of the general stress response (GSR), a transcriptional response under the control of the alternative sigma factor sigma B (σB) that reconfigures gene transcription to provide homeostatic and protective functions to cope with the stress. Within the host σB also plays a key role in surviving the harsh conditions found in the gastrointestinal tract. As the infection progresses beyond the GI tract L. monocytogenes uses an intracellular infectious cycle to propagate, spread and remain protected from the host’s humoral immunity. Many of the virulence genes that facilitate this infectious cycle are under the control of a master transcriptional regulator called PrfA. In this review we consider the environmental reservoirs that enable L. monocytogenes to gain access to the food chain and discuss the stresses that the pathogen must overcome to survive and grow in these environments. The overlap that exists between stress tolerance and virulence is described. We review the principal measures that are used to control the pathogen and point to exciting new approaches that might provide improved means of control in the future. PMID:27933042

Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions

PubMed Central

Lehnert, Teresa; Timme, Sandra; Pollmächer, Johannes; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-01-01

Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole-blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation. PMID:26150807

Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions.

PubMed

Lehnert, Teresa; Timme, Sandra; Pollmächer, Johannes; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-01-01

Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole-blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation.

Adenoviral vaccine induction of CD8+ T cell memory inflation: Impact of co-infection and infection order.

PubMed

Lee, Lian N; Bolinger, Beatrice; Banki, Zoltan; de Lara, Catherine; Highton, Andrew J; Colston, Julia M; Hutchings, Claire; Klenerman, Paul

2017-12-01

The efficacies of many new T cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory CD8 T cells. However, it is now increasingly recognized that prior infection history impacts on the host immune response. Additionally, the order in which these infections are acquired could have a major effect. Exploiting the ability to generate large sustained effector memory (i.e. inflationary) T cell populations from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, the impact of new infections on pre-existing memory and the capacity of the host's memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model. Simultaneous and sequential infections, first with MCMV followed by Ad-lacZ, generated inflationary populations towards both viruses with similar kinetics and magnitude to mono-infected groups. However, in Ad-lacZ immune mice, subsequent acute MCMV infection led to a rapid decline of the pre-existing Ad-LacZ-specific inflating population, associated with bystander activation of Fas-dependent apoptotic pathways. However, responses were maintained long-term and boosting with Ad-lacZ led to rapid re-expansion of the inflating population. These data indicate firstly that multiple specificities of inflating memory cells can be acquired at different times and stably co-exist. Some acute infections may also deplete pre-existing memory populations, thus revealing the importance of the order of infection acquisition. Importantly, immunization with an AdHu5 vector did not alter the size of the pre-existing memory. These phenomena are relevant to the development of adenoviral vectors as novel vaccination strategies for diverse infections and cancers. (241 words).

Adenoviral vaccine induction of CD8+ T cell memory inflation: Impact of co-infection and infection order

PubMed Central

Bolinger, Beatrice; de Lara, Catherine; Hutchings, Claire

2017-01-01

The efficacies of many new T cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory CD8 T cells. However, it is now increasingly recognized that prior infection history impacts on the host immune response. Additionally, the order in which these infections are acquired could have a major effect. Exploiting the ability to generate large sustained effector memory (i.e. inflationary) T cell populations from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, the impact of new infections on pre-existing memory and the capacity of the host’s memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model. Simultaneous and sequential infections, first with MCMV followed by Ad-lacZ, generated inflationary populations towards both viruses with similar kinetics and magnitude to mono-infected groups. However, in Ad-lacZ immune mice, subsequent acute MCMV infection led to a rapid decline of the pre-existing Ad-LacZ-specific inflating population, associated with bystander activation of Fas-dependent apoptotic pathways. However, responses were maintained long-term and boosting with Ad-lacZ led to rapid re-expansion of the inflating population. These data indicate firstly that multiple specificities of inflating memory cells can be acquired at different times and stably co-exist. Some acute infections may also deplete pre-existing memory populations, thus revealing the importance of the order of infection acquisition. Importantly, immunization with an AdHu5 vector did not alter the size of the pre-existing memory. These phenomena are relevant to the development of adenoviral vectors as novel vaccination strategies for diverse infections and cancers. (241 words) PMID:29281733

Ambient ozone and pulmonary innate immunity

PubMed Central

Al-Hegelan, Mashael; Tighe, Robert M.; Castillo, Christian; Hollingsworth, John W.

2013-01-01

Ambient ozone is a criteria air pollutant that impacts both human morbidity and mortality. The effect of ozone inhalation includes both toxicity to lung tissue and alteration of the host immunologic response. The innate immune system facilitates immediate recognition of both foreign pathogens and tissue damage. Emerging evidence supports that ozone can modify the host innate immune response and that this response to inhaled ozone is dependent on genes of innate immunity. Improved understanding of the complex interaction between environmental ozone and host innate immunity will provide fundamental insight into the pathogenesis of inflammatory airways disease. We review the current evidence supporting that environmental ozone inhalation: (1) modifies cell types required for intact innate immunity, (2) is partially dependent on genes of innate immunity, (3) primes pulmonary innate immune responses to LPS, and (4) contributes to innate-adaptive immune system cross-talk. PMID:21132467

Evaluating the importance of faecal sources in human-impacted waters.

PubMed

Schoen, Mary E; Soller, Jeffrey A; Ashbolt, Nicholas J

2011-04-01

Quantitative microbial risk assessment (QMRA) was used to evaluate the relative contribution of faecal indicators and pathogens when a mixture of human sources impacts a recreational waterbody. The waterbody was assumed to be impacted with a mixture of secondary-treated disinfected municipal wastewater and untreated (or poorly treated) sewage, using Norovirus as the reference pathogen and enterococci as the reference faecal indicator. The contribution made by each source to the total waterbody volume, indicator density, pathogen density, and illness risk was estimated for a number of scenarios that accounted for pathogen and indicator inactivation based on the age of the effluent (source-to-receptor), possible sedimentation of microorganisms, and the addition of a non-pathogenic source of faecal indicators (such as old sediments or an animal population with low occurrence of human-infectious pathogens). The waterbody indicator density was held constant at 35 CFU 100 mL(-1) enterococci to compare results across scenarios. For the combinations evaluated, either the untreated sewage or the non-pathogenic source of faecal indicators dominated the recreational waterbody enterococci density assuming a culture method. In contrast, indicator density assayed by qPCR, pathogen density, and bather gastrointestinal illness risks were largely dominated by secondary disinfected municipal wastewater, with untreated sewage being increasingly less important as the faecal indicator load increased from a non-pathogenic source. The results support the use of a calibrated qPCR total enterococci indicator, compared to a culture-based assay, to index infectious human enteric viruses released in treated human wastewater, and illustrate that the source contributing the majority of risk in a mixture may be overlooked when only assessing faecal indicators by a culture-based method. Published by Elsevier Ltd.

Design and descriptive epidemiology of the Infectious Diseases of East African Livestock (IDEAL) project, a longitudinal calf cohort study in western Kenya

PubMed Central

2013-01-01

Background There is a widely recognised lack of baseline epidemiological data on the dynamics and impacts of infectious cattle diseases in east Africa. The Infectious Diseases of East African Livestock (IDEAL) project is an epidemiological study of cattle health in western Kenya with the aim of providing baseline epidemiological data, investigating the impact of different infections on key responses such as growth, mortality and morbidity, the additive and/or multiplicative effects of co-infections, and the influence of management and genetic factors. A longitudinal cohort study of newborn calves was conducted in western Kenya between 2007-2009. Calves were randomly selected from all those reported in a 2 stage clustered sampling strategy. Calves were recruited between 3 and 7 days old. A team of veterinarians and animal health assistants carried out 5-weekly, clinical and postmortem visits. Blood and tissue samples were collected in association with all visits and screened using a range of laboratory based diagnostic methods for over 100 different pathogens or infectious exposures. Results The study followed the 548 calves over the first 51 weeks of life or until death and when they were reported clinically ill. The cohort experienced a high all cause mortality rate of 16% with at least 13% of these due to infectious diseases. Only 307 (6%) of routine visits were classified as clinical episodes, with a further 216 reported by farmers. 54% of calves reached one year without a reported clinical episode. Mortality was mainly to east coast fever, haemonchosis, and heartwater. Over 50 pathogens were detected in this population with exposure to a further 6 viruses and bacteria. Conclusion The IDEAL study has demonstrated that it is possible to mount population based longitudinal animal studies. The results quantify for the first time in an animal population the high diversity of pathogens a population may have to deal with and the levels of co-infections with key pathogens such as Theileria parva. This study highlights the need to develop new systems based approaches to study pathogens in their natural settings to understand the impacts of co-infections on clinical outcomes and to develop new evidence based interventions that are relevant. PMID:24000820

Design and descriptive epidemiology of the Infectious Diseases of East African Livestock (IDEAL) project, a longitudinal calf cohort study in western Kenya.

PubMed

de Clare Bronsvoort, Barend Mark; Thumbi, Samuel Mwangi; Poole, Elizabeth Jane; Kiara, Henry; Auguet, Olga Tosas; Handel, Ian Graham; Jennings, Amy; Conradie, Ilana; Mbole-Kariuki, Mary Ndila; Toye, Philip G; Hanotte, Olivier; Coetzer, J A W; Woolhouse, Mark E J

2013-08-30

There is a widely recognised lack of baseline epidemiological data on the dynamics and impacts of infectious cattle diseases in east Africa. The Infectious Diseases of East African Livestock (IDEAL) project is an epidemiological study of cattle health in western Kenya with the aim of providing baseline epidemiological data, investigating the impact of different infections on key responses such as growth, mortality and morbidity, the additive and/or multiplicative effects of co-infections, and the influence of management and genetic factors.A longitudinal cohort study of newborn calves was conducted in western Kenya between 2007-2009. Calves were randomly selected from all those reported in a 2 stage clustered sampling strategy. Calves were recruited between 3 and 7 days old. A team of veterinarians and animal health assistants carried out 5-weekly, clinical and postmortem visits. Blood and tissue samples were collected in association with all visits and screened using a range of laboratory based diagnostic methods for over 100 different pathogens or infectious exposures. The study followed the 548 calves over the first 51 weeks of life or until death and when they were reported clinically ill. The cohort experienced a high all cause mortality rate of 16% with at least 13% of these due to infectious diseases. Only 307 (6%) of routine visits were classified as clinical episodes, with a further 216 reported by farmers. 54% of calves reached one year without a reported clinical episode. Mortality was mainly to east coast fever, haemonchosis, and heartwater. Over 50 pathogens were detected in this population with exposure to a further 6 viruses and bacteria. The IDEAL study has demonstrated that it is possible to mount population based longitudinal animal studies. The results quantify for the first time in an animal population the high diversity of pathogens a population may have to deal with and the levels of co-infections with key pathogens such as Theileria parva. This study highlights the need to develop new systems based approaches to study pathogens in their natural settings to understand the impacts of co-infections on clinical outcomes and to develop new evidence based interventions that are relevant.

Protective mucosal Th2 immune response against Toxoplasma gondii by murine mesenteric lymph node dendritic cells.

PubMed

Dimier-Poisson, Isabelle; Aline, Fleur; Mévélec, Marie-Noëlle; Beauvillain, Céline; Buzoni-Gatel, Dominique; Bout, Daniel

2003-09-01

Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response to T. gondii. Despite considerable effort, Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo with T. gondii antigens (TAg) as a novel investigation approach to vaccination against T. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosal Toxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity to T. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.

Tropospheric ozone as a fungal elicitor.

PubMed

Zuccarini, Paolo

2009-03-01

Tropospheric ozone has been proven to trigger biochemical plant responses that are similar to the ones induced by an attack of fungal pathogens,i.e. it resembles fungal elicitors.This suggests that ozone can represent a valid tool for the study of stress responses and induction of resistance to pathogens. This review provides an overview of the implications of such a phenomenon for basic and applied research. After an introduction about the environmental implications of tropospheric ozone and plant responses to biotic stresses, the biochemistry of ozone stress is analysed, pointing out its similarities with plant responses to pathogens and its possible applications.

LAMP detection assays for boxwood blight pathogens: a comparative genomics approach

USDA-ARS?s Scientific Manuscript database

Rapid and accurate molecular diagnostic tools are critical to efforts to minimize the impact and spread of emergent pathogens. The identification of diagnostic markers for novel pathogens presents several challenges, especially in the absence of information about population diversity, and where gen...

The effect of agrochemicals on indicator bacteria densities in outdoor mesocosms.

PubMed

Staley, Zachery R; Rohr, Jason R; Harwood, Valerie J

2010-12-01

Water bodies, which are monitored for microbial water quality by quantification of faecal indicator organisms (IOs), can contain various zoonotic pathogens contributed by livestock waste and other sources. Sediments can serve as reservoirs of IOs and other enteric microorganisms, including pathogens. Agrochemicals may influence the survival of these microorganisms in water bodies impacted by livestock waste by enhancing or reducing their survival. Complex, 1100 l, freshwater mesocosms containing leaf litter, zooplankton, periphyton, phytoplankton, and invertebrate and vertebrate animals were used to investigate the response of Escherichia coli and enterococci to agrochemicals. Replicate tanks were treated with atrazine, malathion, chlorothalonil and inorganic fertilizer, either alone at 1× or 2× their expected environmental concentrations (EECs) or in pair-wise combinations at their EECs. IOs inoculated in sediment (∼10⁴ cfu per 100 ml) were enumerated over 28 days. IOs generally declined over time, but manova revealed that addition of fertilizer and atrazine resulted in significantly greater IO densities. Malathion, chlorothalonil and agrochemical concentration (1× vs 2×) did not significantly affect IO densities and no significant interactions between agrochemicals were noted. The augmentation of IO densities in sediments by fertilizer and atrazine may impact their reliability as accurate predictors of water quality and human health risk, and indicates the need for a better understanding of the fate of IOs and enteric pathogens in sediments exposed to agrochemicals. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Host–Multi-Pathogen Warfare: Pathogen Interactions in Co-infected Plants

PubMed Central

Abdullah, Araz S.; Moffat, Caroline S.; Lopez-Ruiz, Francisco J.; Gibberd, Mark R.; Hamblin, John; Zerihun, Ayalsew

2017-01-01

Studies of plant–pathogen interactions have historically focused on simple models of infection involving single host-single disease systems. However, plant infections often involve multiple species and/or genotypes and exhibit complexities not captured in single host-single disease systems. Here, we review recent insights into co-infection systems focusing on the dynamics of host-multi-pathogen interactions and the implications for host susceptibility/resistance. In co-infection systems, pathogen interactions include: (i) Competition, in which competing pathogens develop physical barriers or utilize toxins to exclude competitors from resource-dense niches; (ii) Cooperation, whereby pathogens beneficially interact, by providing mutual biochemical signals essential for pathogenesis, or through functional complementation via the exchange of resources necessary for survival; (iii) Coexistence, whereby pathogens can stably coexist through niche specialization. Furthermore, hosts are also able to, actively or passively, modulate niche competition through defense responses that target at least one pathogen. Typically, however, virulent pathogens subvert host defenses to facilitate infection, and responses elicited by one pathogen may be modified in the presence of another pathogen. Evidence also exists, albeit rare, of pathogens incorporating foreign genes that broaden niche adaptation and improve virulence. Throughout this review, we draw upon examples of co-infection systems from a range of pathogen types and identify outstanding questions for future innovation in disease control strategies. PMID:29118773

Nonhost Resistance of Barley to Different Fungal Pathogens Is Associated with Largely Distinct, Quantitative Transcriptional Responses1[W][OA

PubMed Central

Zellerhoff, Nina; Himmelbach, Axel; Dong, Wubei; Bieri, Stephane; Schaffrath, Ulrich; Schweizer, Patrick

2010-01-01

Nonhost resistance protects plants against attack by the vast majority of potential pathogens, including phytopathogenic fungi. Despite its high biological importance, the molecular architecture of nonhost resistance has remained largely unexplored. Here, we describe the transcriptional responses of one particular genotype of barley (Hordeum vulgare subsp. vulgare ‘Ingrid’) to three different pairs of adapted (host) and nonadapted (nonhost) isolates of fungal pathogens, which belong to the genera Blumeria (powdery mildew), Puccinia (rust), and Magnaporthe (blast). Nonhost resistance against each of these pathogens was associated with changes in transcript abundance of distinct sets of nonhost-specific genes, although general (not nonhost-associated) transcriptional responses to the different pathogens overlapped considerably. The powdery mildew- and blast-induced differences in transcript abundance between host and nonhost interactions were significantly correlated with differences between a near-isogenic pair of barley lines that carry either the Mlo wild-type allele or the mutated mlo5 allele, which mediates basal resistance to powdery mildew. Moreover, during the interactions of barley with the different host or nonhost pathogens, similar patterns of overrepresented and underrepresented functional categories of genes were found. The results suggest that nonhost resistance and basal host defense of barley are functionally related and that nonhost resistance to different fungal pathogens is associated with more robust regulation of complex but largely nonoverlapping sets of pathogen-responsive genes involved in similar metabolic or signaling pathways. PMID:20172964

Host Identity Matters in the Amphibian-Batrachochytrium dendrobatidis System: Fine-Scale Patterns of Variation in Responses to a Multi-Host Pathogen

PubMed Central

Gervasi, Stephanie; Gondhalekar, Carmen; Olson, Deanna H.; Blaustein, Andrew R.

2013-01-01

Species composition within ecological assemblages can drive disease dynamics including pathogen invasion, spread, and persistence. In multi-host pathogen systems, interspecific variation in responses to infection creates important context dependency when predicting the outcome of disease. Here, we examine the responses of three sympatric host species to a single fungal pathogen, Batrachochytrium dendrobatidis, which is associated with worldwide amphibian population declines and extinctions. Using an experimental approach, we show that amphibian species from three different genera display significant differences in patterns of pathgen-induced mortality as well as the magnitude and temporal dynamics of infection load. We exposed amphibians to one of four inoculation dose treatments at both larval and post- metamorphic stages and quantified infection load on day 8 and day 15 post-inoculation. Of the three species examined, only one (the Pacific treefrog; Pseudacris regilla) displayed “dose-dependent” responses; survival was reduced and infection load was elevated as inoculation dose was increased. We observed a reduction in survival but no differences in infection load across pathogen treatments in Cascades frogs (Rana cascadae). Western toads (Anaxyrus boreas) displayed differences in infection load but no differences in survival across pathogen treatments. Within species, responses to the pathogen varied with life history stage, and the most heavily infected species at the larval stage was different from the most heavily infected species at the post-metamorphic stage. Temporal changes in infection load were species and life history stage-specific. We show that variation in susceptibility to this multi-host pathogen is complex when viewed at a fine-scale and may be mediated through intrinsic host traits. PMID:23382904

Endoplasmic Reticulum Stress and Obesity.

PubMed

Yilmaz, Erkan

2017-01-01

In recent years, the world has seen an alarming increase in obesity and closely associated with insulin resistance which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) play in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably other causes for obesity-related insulin resistance and inflammation. One of these appears to be endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.

Food for contagion: Synthesis and future directions for studying host–parasite responses to resource shifts in anthropogenic environments

PubMed Central

Altizer, Sonia. M.; Becker, Daniel J.; Epstein, Jonathan H.; Forbes, Kristian M.; Gillespie, Thomas R.; Hall, Richard J.; Hawley, Dana; Hernandez, Sonia M.; Martin, Lynn B.; Plowright, Raina K.; Satterfield, Dara A.; Streicker, Daniel G.

2018-01-01

Human-provided resource subsidies for wildlife are diverse, common, and have profound consequences for wildlife–pathogen interactions, as demonstrated by papers in this themed issue spanning empirical, theoretical, and management perspectives from a range of study systems. Contributions cut across scales of organization, from the within-host dynamics of immune function, to population-level impacts on parasite transmission, to landscape- and regional-scale patterns of infection. In this concluding paper, we identify common threads and key findings from author contributions, including the consequences of resource subsidies for (i) host immunity; (ii) animal aggregation and contact rates; (iii) host movement and landscape-level infection patterns; and (iv) inter-specific contacts and cross-species transmission. Exciting avenues for future work include studies that integrate mechanistic modeling and empirical approaches to better explore cross-scale processes, and experimental manipulations of food resources to quantify host and pathogen responses. Work is also needed to examine evolutionary responses to provisioning, and ask how diet-altered changes to the host microbiome influence infection processes. Given the massive public health and conservation implications of anthropogenic resource shifts, we end by underscoring the need for practical recommendations to manage supplemental feeding practices, limit human–wildlife conflicts over shared food resources, and reduce cross-species transmission risks, including to humans. PMID:29531154

Nutritional modulation of resistance to infectious diseases.

PubMed

Klasing, K C

1998-08-01

Dietary characteristics can modulate a bird's susceptibility to infectious challenges and subtle influences due to the level of nutrients or the types of ingredients may at times be of critical importance. This review considers seven mechanisms for nutritional modulation of resistance to infectious disease in poultry. 1) Nutrition may impact the development of the immune system, both in ovo and in the first weeks posthatch. Micronutrient deficiencies that affect developmental events, such as the seeding of lymphoid organs and clonal expansion of lymphocyte clones, can negatively impact the immune system later in life. 2) A substrate role of nutrients is necessary for the immune response so that responding cells can divide and synthesize effector molecules. The quantitative need for nutrients for supporting a normal immune system, as well as the proliferation of leukocytes and the production of antibodies during an infectious challenge, is very small relative to uses for growth or egg production. It is likely that the systemic acute phase response that accompanies most infectious challenges is a more significant consumer of nutrients than the immune system itself. 3) The low concentration of some nutrients (e.g., iron) in body fluids makes them the limiting substrates for the proliferation of invading pathogens and the supply of these nutrients is further limited during the immune response. 4) Some nutrients (e.g., fatty acids and vitamins A, D, and E) have direct regulatory actions on leukocytes by binding to intracellular receptors or by modifying the release of second messengers. 5) The diet may also have indirect regulatory effects that are mediated by the classical endocrine system. 6) Physical and chemical aspects of the diet can modify the populations of microorganisms in the gastrointestinal tract, the capacity of pathogens to attach to enterocytes, and the integrity of the intestinal epithelium.

Helminths as vectors of pathogens in vertebrate hosts: a theoretical approach.

PubMed

Perkins, Sarah E; Fenton, Andy

2006-07-01

Pathogens frequently use vectors to facilitate transmission between hosts and, for vertebrate hosts, the vectors are typically ectoparasitic arthropods. However, other parasites that are intimately associated with their hosts may also be ideal candidate vectors; namely the parasitic helminths. Here, we present empirical evidence that helminth vectoring of pathogens occurs in a range of vertebrate systems by a variety of helminth taxa. Using a novel theoretical framework we explore the dynamics of helminth vectoring and determine which host-helminth-pathogen characteristics may favour the evolution of helminth vectoring. We use two theoretical models: the first is a population dynamic model amalgamated from standard macro- and microparasite models, which serves as a framework for investigation of within-host interactions between co-infecting pathogens and helminths. The second is an evolutionary model, which we use to predict the ecological conditions under which we would expect helminth vectoring to evolve. We show that, like arthropod vectors, helminth vectors increase pathogen fitness. However, unlike arthropod vectors, helminth vectoring increases the pathogenic impact on the host and may allow the evolution of high pathogen virulence. We show that concomitant infection of a host with a helminth and pathogen are not necessarily independent of one another, due to helminth vectoring of microparasites, with profound consequences for pathogen persistence and the impact of disease on the host population.

Ionic Liquids as Unforeseen Assets to Fight Life-Threatening Mycotic Diseases.

PubMed

Hartmann, Diego O; Petkovic, Marija; Silva Pereira, Cristina

2016-01-01

Ionic liquids discovery has celebrated 100 years. They consist solely of ions, one of which is typically organic and asymmetrical. Remarkable physical and chemical properties stirred their use as alternative solvents in many chemical processes. The recent demonstration of their occurrence in nature might boost their interest in biological sciences. In the search of mechanistic understandings of ionic liquids' ecotoxicological impacts in fungi, we have analyzed the proteome, transcriptome, and metabolome responses to this chemical stress. Data illuminated new hypotheses that altered our research path - exploit ionic liquids as tools for the discovery of pathways and metabolites that may impact fungal development and pathogenicity. As we get closer to solve the primary effects of each ionic liquid family and their specific gene targets, the vision of developing antifungal ionic liquids and/or materials, by taking advantage of elegant progresses in this field, might become a reality. Task-designed formulations may improve the performance of conventional antifungal drugs, build functional coatings for reducing allergens production, or aid in the recovery of antifungal plant polymers. The frontier research in this cross-disciplinary field may provide us unforeseen means to address the global concern of mycotic diseases. Pathogenic and opportunistic fungi are responsible for numerous infections, killing annually nearly 1.5 million immunocompromised individuals worldwide, a similar rate to malaria or tuberculosis. This perspective will review our major findings and current hypotheses, contextualizing how they might bring us closer to efficient strategies to prevent and fight mycotic diseases.

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

PubMed

Kurian, Allison W; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Hawley, Sarah T; Morrow, Monica; McLeod, M Chandler; Jagsi, Reshma; Katz, Steven J

2017-07-10

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.

Sucrose and invertases, a part of the plant defense response to the biotic stresses

PubMed Central

Tauzin, Alexandra S.; Giardina, Thierry

2014-01-01

Sucrose is the main form of assimilated carbon which is produced during photosynthesis and then transported from source to sink tissues via the phloem. This disaccharide is known to have important roles as signaling molecule and it is involved in many metabolic processes in plants. Essential for plant growth and development, sucrose is engaged in plant defense by activating plant immune responses against pathogens. During infection, pathogens reallocate the plant sugars for their own needs forcing the plants to modify their sugar content and triggering their defense responses. Among enzymes that hydrolyze sucrose and alter carbohydrate partitioning, invertases have been reported to be affected during plant-pathogen interactions. Recent highlights on the role of invertases in the establishment of plant defense responses suggest a more complex regulation of sugar signaling in plant-pathogen interaction. PMID:25002866

Innate signaling by mycobacterial cell wall components and relevance for development of adjuvants for subunit vaccines.

PubMed

Tima, Hermann Giresse; Huygen, Kris; Romano, Marta

2016-11-01

Pathogen recognition receptors (PRRs) recognize pathogen-associated molecular patterns, triggering the induction of inflammatory innate responses and contributing to the development of specific adaptive immune responses. Novel adjuvants have been developed based on agonists of PRRs. Areas covered: Lipid pathogen-associated molecular patterns (PAMPs) present in the cell wall of mycobacteria are revised, with emphasis on agonists of C-type lectin receptors, signaling pathways, and preclinical data supporting their use as novel adjuvants inducing cell-mediated immune responses. Their potential use as lipid antigens in novel tuberculosis subunit vaccines is also discussed. Expert commentary: Few adjuvants are licensed for human use and mainly favour antibody-mediated protective immunity. Use of lipid PAMPs that trigger cell-mediated immune responses could lead to the development of adjuvants for vaccines against intracellular pathogens and cancer.

Proteomic Characterization of Host Response to Yersinia pestis

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

Chromy, B; Perkins, J; Heidbrink, J

Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct formore » the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.« less

Development of model infectious disease protocols for fire and EMS personnel.

PubMed

Miller, Nancy L; Gudmestad, Tom; Eisenberg, Mickey S

2005-01-01

To develop model infectious disease exposure plans for emergency medical services agencies in King County, Washington. All fire departments in King County, Washington, were surveyed to determine their pathogen exposure policies. After these agencies were surveyed, model response plans were developed for both bloodborne and airborne pathogen exposure. Twenty-four of the 35 fire departments in King County submitted infectious disease exposure policies. There was diversity among the plans, and not all were deemed able to provide prophylaxis in a timely fashion. Based on this lack of uniformity among response plans, model response plans were developed for bloodborne and airborne infectious disease pathogens. Great variety was present throughout the exposure plans currently in use throughout King County, Washington. Model plans would likely universalize response to pathogen exposure and help to ensure prompt and appropriate postexposure prophylaxis.

Accessible and inexpensive tools for global HPAI surveillance: A mobile-phone based system.

PubMed

Lin, Yibo; Heffernan, Claire

2011-02-01

Highly pathogenic avian influenza (HPAI) disproportionately impacts poor livestock keepers in southern countries. Although the estimated cost of the disease in the billions, response to the epidemic remains fragmented and information channels slow. Given the continuing threat of outbreaks, and what appears to be the politicisation of outbreak reporting, new tools are needed to enforce transparency in stakeholder communication. In response to this need, we created a mobile-phone based surveillance system to aid critical information transfer among policy makers, practitioners and the poor themselves. The tool operates at the local, national and global levels and further links decision-makers to international databases. Copyright © 2010 Elsevier B.V. All rights reserved.

Subcontinental impacts of an invasive tree disease on forest structure and dynamics

Treesearch

Jeffrey R. Garnas; Matthew P. Ayres; Andrew M. Liebhold; Celia. Evans

2011-01-01

Introduced pests and pathogens are a major source of disturbance to ecosystems world-wide. The famous examples have produced dramatic reductions in host abundance, including virtual extirpation, but most introductions have more subtle impacts that are hard to quantify but are potentially at least as important due to the pathogens' effects on host reproduction,...

Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay

USDA-ARS?s Scientific Manuscript database

Highly pathogenic avian influenza virus (HPAIV) infections in chickens produce a negative impact on egg production, and virus is deposited on surface and internal contents of eggs. Previously, vaccination maintained egg production and reduced egg contamination when challenged with a North American H...

Foliar aphid feeding recruits rhizosphere bacteria and primes plant immunity against pathogenic and non-pathogenic bacteria in pepper.

PubMed

Lee, Boyoung; Lee, Soohyun; Ryu, Choong-Min

2012-07-01

Plants modulate defence signalling networks in response to different biotic stresses. The present study evaluated the effect of a phloem-sucking aphid on plant defence mechanisms in pepper (Capsicum annuum) during subsequent pathogen attacks on leaves and rhizosphere bacteria on roots. Plants were pretreated with aphids and/or the chemical trigger benzothiadiazol (BTH) 7 d before being challenged with two pathogenic bacteria, Xanthomonas axonopodis pv. vesicatoria (Xav) as a compatible pathogen and X. axonopodis pv. glycines (Xag) as an incompatible (non-host) pathogen. Disease severity was noticeably lower in aphid- and BTH + aphid-treated plants than in controls. Although treatment with BTH or aphids alone did not affect the hypersensitive response (HR) against Xag strain 8ra, the combination treatment had a synergistic effect on the HR. The aphid population was reduced by BTH pretreatment and by combination treatment with BTH and bacterial pathogens in a synergistic manner. Analysis of the expression of the defence-related genes Capsicum annum pathogenesis-related gene 9 (CaPR9), chitinase 2 (CaCHI2), SAR8·2 and Lipoxygenase1 (CaLOX1) revealed that aphid infestation resulted in the priming of the systemic defence responses against compatible and incompatible pathogens. Conversely, pre-challenge with the compatible pathogen Xav on pepper leaves significantly reduced aphid numbers. Aphid infestation increased the population of the beneficial Bacillus subtilis GB03 but reduced that of the pathogenic Ralstonia solanacearum SL1931. The expression of defence-related genes in the root and leaf after aphid feeding indicated that the above-ground aphid infestation elicited salicylic acid and jasmonic acid signalling throughout the whole plant. The findings of this study show that aphid feeding elicits plant resistance responses and attracts beneficial bacterial populations to help the plant cope with subsequent pathogen attacks.

Foliar aphid feeding recruits rhizosphere bacteria and primes plant immunity against pathogenic and non-pathogenic bacteria in pepper

PubMed Central

Lee, Boyoung; Lee, Soohyun; Ryu, Choong-Min

2012-01-01

Background and Aims Plants modulate defence signalling networks in response to different biotic stresses. The present study evaluated the effect of a phloem-sucking aphid on plant defence mechanisms in pepper (Capsicum annuum) during subsequent pathogen attacks on leaves and rhizosphere bacteria on roots. Methods Plants were pretreated with aphids and/or the chemical trigger benzothiadiazol (BTH) 7 d before being challenged with two pathogenic bacteria, Xanthomonas axonopodis pv. vesicatoria (Xav) as a compatible pathogen and X. axonopodis pv. glycines (Xag) as an incompatible (non-host) pathogen. Key Results Disease severity was noticeably lower in aphid- and BTH + aphid-treated plants than in controls. Although treatment with BTH or aphids alone did not affect the hypersensitive response (HR) against Xag strain 8ra, the combination treatment had a synergistic effect on the HR. The aphid population was reduced by BTH pretreatment and by combination treatment with BTH and bacterial pathogens in a synergistic manner. Analysis of the expression of the defence-related genes Capsicum annum pathogenesis-related gene 9 (CaPR9), chitinase 2 (CaCHI2), SAR8·2 and Lipoxygenase1 (CaLOX1) revealed that aphid infestation resulted in the priming of the systemic defence responses against compatible and incompatible pathogens. Conversely, pre-challenge with the compatible pathogen Xav on pepper leaves significantly reduced aphid numbers. Aphid infestation increased the population of the beneficial Bacillus subtilis GB03 but reduced that of the pathogenic Ralstonia solanacearum SL1931. The expression of defence-related genes in the root and leaf after aphid feeding indicated that the above-ground aphid infestation elicited salicylic acid and jasmonic acid signalling throughout the whole plant. Conclusions The findings of this study show that aphid feeding elicits plant resistance responses and attracts beneficial bacterial populations to help the plant cope with subsequent pathogen attacks. PMID:22437662

The Impact of Recombination Hotspots on Genome Evolution of a Fungal Plant Pathogen

PubMed Central

Croll, Daniel; Lendenmann, Mark H.; Stewart, Ethan; McDonald, Bruce A.

2015-01-01

Recombination has an impact on genome evolution by maintaining chromosomal integrity, affecting the efficacy of selection, and increasing genetic variability in populations. Recombination rates are a key determinant of the coevolutionary dynamics between hosts and their pathogens. Historic recombination events created devastating new pathogens, but the impact of ongoing recombination in sexual pathogens is poorly understood. Many fungal pathogens of plants undergo regular sexual cycles, and sex is considered to be a major factor contributing to virulence. We generated a recombination map at kilobase-scale resolution for the haploid plant pathogenic fungus Zymoseptoria tritici. To account for intraspecific variation in recombination rates, we constructed genetic maps from two independent crosses. We localized a total of 10,287 crossover events in 441 progeny and found that recombination rates were highly heterogeneous within and among chromosomes. Recombination rates on large chromosomes were inversely correlated with chromosome length. Short accessory chromosomes often lacked evidence for crossovers between parental chromosomes. Recombination was concentrated in narrow hotspots that were preferentially located close to telomeres. Hotspots were only partially conserved between the two crosses, suggesting that hotspots are short-lived and may vary according to genomic background. Genes located in hotspot regions were enriched in genes encoding secreted proteins. Population resequencing showed that chromosomal regions with high recombination rates were strongly correlated with regions of low linkage disequilibrium. Hence, genes in pathogen recombination hotspots are likely to evolve faster in natural populations and may represent a greater threat to the host. PMID:26392286

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem[OPEN

PubMed Central

Eshbaugh, Robert; Chen, Fang; Atwell, Susana

2017-01-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how the host’s defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea. This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. PMID:29042403

De Novo Assembled Wheat Transcriptomes Delineate Differentially Expressed Host Genes in Response to Leaf Rust Infection.

PubMed

Chandra, Saket; Singh, Dharmendra; Pathak, Jyoti; Kumari, Supriya; Kumar, Manish; Poddar, Raju; Balyan, Harindra Singh; Gupta, Puspendra Kumar; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2016-01-01

Pathogens like Puccinia triticina, the causal organism for leaf rust, extensively damages wheat production. The interaction at molecular level between wheat and the pathogen is complex and less explored. The pathogen induced response was characterized using mock- or pathogen inoculated near-isogenic wheat lines (with or without seedling leaf rust resistance gene Lr28). Four Serial Analysis of Gene Expression libraries were prepared from mock- and pathogen inoculated plants and were subjected to Sequencing by Oligonucleotide Ligation and Detection, which generated a total of 165,767,777 reads, each 35 bases long. The reads were processed and multiple k-mers were attempted for de novo transcript assembly; 22 k-mers showed the best results. Altogether 21,345 contigs were generated and functionally characterized by gene ontology annotation, mining for transcription factors and resistance genes. Expression analysis among the four libraries showed extensive alterations in the transcriptome in response to pathogen infection, reflecting reorganizations in major biological processes and metabolic pathways. Role of auxin in determining pathogenesis in susceptible and resistant lines were imperative. The qPCR expression study of four LRR-RLK (Leucine-rich repeat receptor-like protein kinases) genes showed higher expression at 24 hrs after inoculation with pathogen. In summary, the conceptual model of induced resistance in wheat contributes insights on defense responses and imparts knowledge of Puccinia triticina-induced defense transcripts in wheat plants.

De Novo Assembled Wheat Transcriptomes Delineate Differentially Expressed Host Genes in Response to Leaf Rust Infection

PubMed Central

Pathak, Jyoti; Kumari, Supriya; Kumar, Manish; Poddar, Raju; Balyan, Harindra Singh; Gupta, Puspendra Kumar; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2016-01-01

Pathogens like Puccinia triticina, the causal organism for leaf rust, extensively damages wheat production. The interaction at molecular level between wheat and the pathogen is complex and less explored. The pathogen induced response was characterized using mock- or pathogen inoculated near-isogenic wheat lines (with or without seedling leaf rust resistance gene Lr28). Four Serial Analysis of Gene Expression libraries were prepared from mock- and pathogen inoculated plants and were subjected to Sequencing by Oligonucleotide Ligation and Detection, which generated a total of 165,767,777 reads, each 35 bases long. The reads were processed and multiple k-mers were attempted for de novo transcript assembly; 22 k-mers showed the best results. Altogether 21,345 contigs were generated and functionally characterized by gene ontology annotation, mining for transcription factors and resistance genes. Expression analysis among the four libraries showed extensive alterations in the transcriptome in response to pathogen infection, reflecting reorganizations in major biological processes and metabolic pathways. Role of auxin in determining pathogenesis in susceptible and resistant lines were imperative. The qPCR expression study of four LRR-RLK (Leucine-rich repeat receptor-like protein kinases) genes showed higher expression at 24 hrs after inoculation with pathogen. In summary, the conceptual model of induced resistance in wheat contributes insights on defense responses and imparts knowledge of Puccinia triticina-induced defense transcripts in wheat plants. PMID:26840746

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem.

PubMed

Zhang, Wei; Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Eshbaugh, Robert; Chen, Fang; Atwell, Susana; Kliebenstein, Daniel J

2017-11-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana - Botrytis cinerea pathosystem to test how the host's defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1 , individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. © 2017 American Society of Plant Biologists. All rights reserved.

Transcription Factors Involved in Plant Resistance to Pathogens.

PubMed

Amorim, Lidiane L B; da Fonseca Dos Santos, Romulo; Neto, Joao Pacífico Bezerra; Guida-Santos, Mauro; Crovella, Sergio; Benko-Iseppon, Ana Maria

2017-01-01

Phytopathogenic microorganisms have a significant influence on survival and productivity of several crop plants. Transcription factors (TFs) are important players in the response to biotic stresses, as insect attack and pathogen infection. In face of such adversities many TFs families have been previously reported as differentially expressed in plants as a reaction to bacterial, fungal and viral infection. This review highlights recent progresses in understanding the structure, function, signal regulation and interaction of transcription factors with other proteins in response to pathogens. Hence, we focus on three families of transcription factors: ERF, bZIP and WRKY, due to their abundance, importance and the availability of functionally well-characterized members in response to pathogen attack. Their roles and the possibilities related to the use of this knowledge for engineering pathogen resistance in crop plants are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biofilms in Water, Its role and impact in human disease transmission

DTIC Science & Technology

2008-01-01

increasing realization of the importance of the world’s oceans as a source of potentially pathogenic microorganisms. Human bacterial pathogens...colorimetric microtitre model for the detection of Staphylococcus aureus biofilms. Lett Appl Microbiol 2008, 46:249-254. A new microplate model for...Polz M: Diversity, sources, and detection of human bacterial pathogens in the marine environment. In Oceans and Health: Pathogens in the Marine

Proximal sensing of plant-pathogen interactions in spring barley with three fluorescence techniques.

PubMed

Leufen, Georg; Noga, Georg; Hunsche, Mauricio

2014-06-24

In the last years fluorescence spectroscopy has come to be viewed as an essential approach in key research fields of applied plant sciences. However, the quantity and particularly the quality of information produced by different equipment might vary considerably. In this study we investigate the potential of three optical devices for the proximal sensing of plant-pathogen interactions in four genotypes of spring barley. For this purpose, the fluorescence lifetime, the image-resolved multispectral fluorescence and selected indices of a portable multiparametric fluorescence device were recorded at 3, 6, and 9 days after inoculation (dai) from healthy leaves as well as from leaves inoculated with powdery mildew (Blumeria graminis) or leaf rust (Puccinia hordei). Genotype-specific responses to pathogen infections were revealed already at 3 dai by higher fluorescence mean lifetimes in the spectral range from 410 to 560 nm in the less susceptible varieties. Noticeable pathogen-induced modifications were also revealed by the 'Blue-to-Far-Red Fluorescence Ratio' and the 'Simple Fluorescence Ratio'. Particularly in the susceptible varieties the differences became more evident in the time-course of the experiment i.e., following the pathogen development. The relevance of the blue and green fluorescence to exploit the plant-pathogen interaction was demonstrated by the multispectral fluorescence imaging system. As shown, mildewed leaves were characterized by exceptionally high blue fluorescence, contrasting the values observed in rust inoculated leaves. Further, we confirm that the intensity of green fluorescence depends on the pathogen infection and the stage of disease development; this information might allow a differentiation of both diseases. Moreover, our results demonstrate that the detection area might influence the quality of the information, although it had a minor impact only in the current study. Finally, we highlight the relevance of different excitation-emission channels to better understand and evaluate plant-physiological alterations due to pathogen infections.

Arabidopsis Heterotrimeric G-Proteins Play a Critical Role in Host and Nonhost Resistance against Pseudomonas syringae Pathogens

PubMed Central

Lee, Seonghee; Rojas, Clemencia M.; Ishiga, Yasuhiro; Pandey, Sona; Mysore, Kirankumar S.

2013-01-01

Heterotrimeric G-proteins have been proposed to be involved in many aspects of plant disease resistance but their precise role in mediating nonhost disease resistance is not well understood. We evaluated the roles of specific subunits of heterotrimeric G-proteins using knock-out mutants of Arabidopsis Gα, Gβ and Gγ subunits in response to host and nonhost Pseudomonas pathogens. Plants lacking functional Gα, Gβ and Gγ1Gγ2 proteins displayed enhanced bacterial growth and disease susceptibility in response to host and nonhost pathogens. Mutations of single Gγ subunits Gγ1, Gγ2 and Gγ3 did not alter bacterial disease resistance. Some specificity of subunit usage was observed when comparing host pathogen versus nonhost pathogen. Overexpression of both Gα and Gβ led to reduced bacterial multiplication of nonhost pathogen P. syringae pv. tabaci whereas overexpression of Gβ, but not of Gα, resulted in reduced bacterial growth of host pathogen P. syringae pv. maculicola, compared to wild-type Col-0. Moreover, the regulation of stomatal aperture by bacterial pathogens was altered in Gα and Gβ mutants but not in any of the single or double Gγ mutants. Taken together, these data substantiate the critical role of heterotrimeric G-proteins in plant innate immunity and stomatal modulation in response to P. syringae. PMID:24349286

Fire blight disease reactome: RNA-seq transcriptional profile of apple host plant defense responses to Erwinia amylovora pathogen infection.

PubMed

Kamber, Tim; Buchmann, Jan P; Pothier, Joël F; Smits, Theo H M; Wicker, Thomas; Duffy, Brion

2016-02-17

The molecular basis of resistance and susceptibility of host plants to fire blight, a major disease threat to pome fruit production globally, is largely unknown. RNA-sequencing data from challenged and mock-inoculated flowers were analyzed to assess the susceptible response of apple to the fire blight pathogen Erwinia amylovora. In presence of the pathogen 1,080 transcripts were differentially expressed at 48 h post inoculation. These included putative disease resistance, stress, pathogen related, general metabolic, and phytohormone related genes. Reads, mapped to regions on the apple genome where no genes were assigned, were used to identify potential novel genes and open reading frames. To identify transcripts specifically expressed in response to E. amylovora, RT-PCRs were conducted and compared to the expression patterns of the fire blight biocontrol agent Pantoea vagans strain C9-1, another apple pathogen Pseudomonas syringae pv. papulans, and mock inoculated apple flowers. This led to the identification of a peroxidase superfamily gene that was lower expressed in response to E. amylovora suggesting a potential role in the susceptibility response. Overall, this study provides the first transcriptional profile by RNA-seq of the host plant during fire blight disease and insights into the response of susceptible apple plants to E. amylovora.

Fire blight disease reactome: RNA-seq transcriptional profile of apple host plant defense responses to Erwinia amylovora pathogen infection

PubMed Central

Kamber, Tim; Buchmann, Jan P.; Pothier, Joël F.; Smits, Theo H. M.; Wicker, Thomas; Duffy, Brion

2016-01-01

The molecular basis of resistance and susceptibility of host plants to fire blight, a major disease threat to pome fruit production globally, is largely unknown. RNA-sequencing data from challenged and mock-inoculated flowers were analyzed to assess the susceptible response of apple to the fire blight pathogen Erwinia amylovora. In presence of the pathogen 1,080 transcripts were differentially expressed at 48 h post inoculation. These included putative disease resistance, stress, pathogen related, general metabolic, and phytohormone related genes. Reads, mapped to regions on the apple genome where no genes were assigned, were used to identify potential novel genes and open reading frames. To identify transcripts specifically expressed in response to E. amylovora, RT-PCRs were conducted and compared to the expression patterns of the fire blight biocontrol agent Pantoea vagans strain C9-1, another apple pathogen Pseudomonas syringae pv. papulans, and mock inoculated apple flowers. This led to the identification of a peroxidase superfamily gene that was lower expressed in response to E. amylovora suggesting a potential role in the susceptibility response. Overall, this study provides the first transcriptional profile by RNA-seq of the host plant during fire blight disease and insights into the response of susceptible apple plants to E. amylovora. PMID:26883568

Real-time monitoring of immune responses under pathogen invasion and drug interference by integrated microfluidic device coupled with worm-based biosensor.

PubMed

Hu, Liang; Ge, Anle; Wang, Xixian; Wang, Shanshan; Yue, Xinpei; Wang, Jie; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

2018-07-01

Immune response to environmental pathogen invasion is a complex process to prevent host from further damage. For quantitatively understanding immune responses and revealing the pathogenic environmental information, real-time monitoring of such a whole dynamic process with single-animal resolution in well-defined environments is highly desired. In this work, an integrated microfluidic device coupled with worm-based biosensor was proposed for in vivo studies of dynamic immune responses and antibiotics interference in infected C. elegans. Individual worms housed in chambers were exposed to the various pathogens and discontinuously manipulated for imaging with limited influence on physiological activities. The expression of immune responses gene (irg-1) was time-lapse measured in intact worms during pathogen infection. Results demonstrated that irg-1 gene could be induced in the presence of P. aeruginosa strain PA14 in a dose-dependent manner, and the survival of infected worm could be rescued under gentamicin or erythromycin treatments. We expect it to be a versatile platform to facilitate future studies on pathogenesis researches and rapid drug screen using C. elegans disease model. Copyright © 2018 Elsevier B.V. All rights reserved.

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome

PubMed Central

Ferlaino, Michael; Rogers, Mark F.; Shihab, Hashem A.; Mort, Matthew; Cooper, David N.; Gaunt, Tom R.; Campbell, Colin

2018-01-01

Background Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. Results We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. Conclusions FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome. PMID:28985712

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.

PubMed

Ferlaino, Michael; Rogers, Mark F; Shihab, Hashem A; Mort, Matthew; Cooper, David N; Gaunt, Tom R; Campbell, Colin

2017-10-06

Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.

Staphylococcus aureus toxin gene hitchhikes on a transferable antibiotic resistance element.

PubMed

Otto, Michael

2010-01-01

Virulence and antibiotic resistance of the dangerous human pathogen Staphylococcus aureus are to large extent determined by the acquisition of mobile genetic elements (MGEs). Up to now, these elements were known to comprise either resistance or virulence determinants, but not a mixture of the two. Queck et al. now found a cytolysin gene of the phenol-soluble modulin (PSM) family within SCCmec elements, which contain methicillin resistance genes and are largely responsible for the spread of methicillin-resistant S. aureus (MRSA). The novel gene, called psm-mec, had a significant impact on virulence in MRSA strains that do not produce high levels of genome-encoded PSMs. This first example of a combination of toxin and resistance genes on one staphylococcal MGE shows that such bundling is possible and may lead to an even faster acquisition of toxin and resistance genes by S. aureus and other staphylococcal pathogens.

Experimental infection of snakes with Ophidiomyces ophiodiicola causes pathological changes that typify snake fungal disease

USGS Publications Warehouse

Lorch, Jeffrey M.; Lankton, Julia S.; Werner, Katrien; Falendysz, Elizabeth A.; McCurley, Kevin; Blehert, David S.

2015-01-01

IMPORTANCE Skin infections in snakes, referred to as snake fungal disease (SFD), have been reported with increasing frequency in wild snakes in the eastern United States. While most of these infections are associated with the fungusOphidiomyces ophiodiicola, there has been no conclusive evidence to implicate this fungus as a primary pathogen. Furthermore, it is not understood why the infections affect different host populations differently. Our experiment demonstrates that O. ophiodiicola is the causative agent of SFD and can elicit pathological changes that likely impact fitness of wild snakes. This information, and the laboratory model we describe, will be essential in addressing unresolved questions regarding disease ecology and outcomes of O. ophiodiicola infection and helping to conserve snake populations threatened by the disease. The SFD model of infection also offers utility for exploring larger concepts related to comparative fungal virulence, host response, and host-pathogen evolution.

Contaminated water delivery as a simple and effective method of experimental Salmonella infection

PubMed Central

O’Donnell, Hope; Pham, Oanh H.; Benoun, Joseph M.; Ravesloot-Chávez, Marietta M.; McSorley, Stephen J.

2016-01-01

Aims In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the gastrointestinal tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. Materials and Methods C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. Results We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 hours allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Conclusions Together, these data question the need for gavage delivery for infection with oral pathogens. PMID:26439708

Tumour necrosis factor receptor trafficking dysfunction opens the TRAPS door to pro-inflammatory cytokine secretion

PubMed Central

Turner, Mark D.; Chaudhry, Anupama; Nedjai, Belinda

2011-01-01

Cytokines are secreted from macrophages and other cells of the immune system in response to pathogens. Additionally, in autoinflammatory diseases cytokine secretion occurs in the absence of pathogenic stimuli. In the case of TRAPS [TNFR (tumour necrosis factor receptor)-associated periodic syndrome], inflammatory episodes result from mutations in the TNFRSF1A gene that encodes TNFR1. This work remains controversial, however, with at least three distinct separate mechanisms of receptor dysfunction having been proposed. Central to these hypotheses are the NF-κB (nuclear factor κB) and MAPK (mitogen-activated protein kinase) families of transcriptional activators that are able to up-regulate expression of a number of genes, including pro-inflammatory cytokines. The present review examines each proposed mechanism of TNFR1 dysfunction, and addresses how these processes might ultimately impact upon cytokine secretion and disease pathophysiology. PMID:22115362

Contaminated water delivery as a simple and effective method of experimental Salmonella infection.

PubMed

O'Donnell, Hope; Pham, Oanh H; Benoun, Joseph M; Ravesloot-Chávez, Marietta M; McSorley, Stephen J

2015-01-01

In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 h allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Together, these data question the need for gavage delivery for infection with oral pathogens.

Iron Overload Is Associated With Oxidative Stress and Nutritional Immunity During Viral Infection in Fish.

PubMed

Tarifeño-Saldivia, Estefanía; Aguilar, Andrea; Contreras, David; Mercado, Luis; Morales-Lange, Byron; Márquez, Katherine; Henríquez, Adolfo; Riquelme-Vidal, Camila; Boltana, Sebastian

2018-01-01

Iron is a trace element, essential to support life due to its inherent ability to exchange electrons with a variety of molecules. The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. During evolution, the shared requirement of micro- and macro-organisms for this important nutrient has shaped the pathogen-host relationship. Infectious pancreatic necrosis virus (IPNv) affects salmonids constituting a sanitary problem for this industry as it has an important impact on post-smolt survival. While immune modulation induced by IPNv infection has been widely characterized on Salmo salar , viral impact on iron host metabolism has not yet been elucidated. In the present work, we evaluate short-term effect of IPNv on several infected tissues from Salmo salar . We observed that IPNv displayed high tropism to headkidney, which directly correlates with a rise in oxidative stress and antiviral responses. Transcriptional profiling on headkidney showed a massive modulation of gene expression, from which biological pathways involved with iron metabolism were remarkable. Our findings suggest that IPNv infection increase oxidative stress on headkidney as a consequence of iron overload induced by a massive upregulation of genes involved in iron metabolism.

Ecology of whirling disease in arid lands with an emphasis on Tibufex tubifex

Treesearch

Robert James Du Bey

2006-01-01

The novel pathogen hypothesis describes host parasite relationships where a pathogen spreads into new geographical areas or into areas of previously unexposed "virgin" hosts. Often, measures of parasite virulence and host resistance are elucidated through pathogenic impacts on the "virgin" hosts. The myxosporean Myxobolus cerebralis...

The early response during the interaction of fungal phytopathogen and host plant.

PubMed

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

2017-05-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

The early response during the interaction of fungal phytopathogen and host plant

PubMed Central

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

2017-01-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

Deletion of the Monkeypox Virus Inhibitor of Complement Enzymes Locus Impacts the Adaptive Immune Response to Monkeypox Virus in a Nonhuman Primate Model of Infection ▿ §

PubMed Central

Estep, Ryan D.; Messaoudi, Ilhem; O'Connor, Megan A.; Li, Helen; Sprague, Jerald; Barron, Alexander; Engelmann, Flora; Yen, Bonnie; Powers, Michael F.; Jones, John M.; Robinson, Bridget A.; Orzechowska, Beata U.; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Wilk, Jennifer; Axthelm, Michael K.; Wong, Scott W.

2011-01-01

Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola virus, the causative agent of smallpox. Human MPXV infection results in a disease that is similar to smallpox and can also be fatal. Two clades of MPXV have been identified, with viruses of the central African clade displaying more pathogenic properties than those within the west African clade. The monkeypox inhibitor of complement enzymes (MOPICE), which is not expressed by viruses of the west African clade, has been hypothesized to be a main virulence factor responsible for increased pathogenic properties of central African strains of MPXV. To gain a better understanding of the role of MOPICE during MPXV-mediated disease, we compared the host adaptive immune response and disease severity following intrabronchial infection with MPXV-Zaire (n = 4), or a recombinant MPXV-Zaire (n = 4) lacking expression of MOPICE in rhesus macaques (RM). Data presented here demonstrate that infection of RM with MPXV leads to significant viral replication in the peripheral blood and lungs and results in the induction of a robust and sustained adaptive immune response against the virus. More importantly, we show that the loss of MOPICE expression results in enhanced viral replication in vivo, as well as a dampened adaptive immune response against MPXV. Taken together, these findings suggest that MOPICE modulates the anti-MPXV immune response and that this protein is not the sole virulence factor of the central African clade of MPXV. PMID:21752919

LysM receptor-like kinases to improve plant defense response against fungal pathogens

DOEpatents

Wan, Jinrong [Columbia, MO; Stacey, Gary [Columbia, MO; Stacey, Minviluz [Columbia, MO; Zhang, Xuecheng [Columbia, MO

2012-01-17

Perception of chitin fragments (chitooligosaccharides) is an important first step in plant defense response against fungal pathogen. LysM receptor-like kinases (LysM RLKs) are instrumental in this perception process. LysM RLKs also play a role in activating transcription of chitin-responsive genes (CRGs) in plants. Mutations in the LysM kinase receptor genes or the downstream CRGs may affect the fungal susceptibility of a plant. Mutations in LysM RLKs or transgenes carrying the same may be beneficial in imparting resistance against fungal pathogens.

LysM receptor-like kinases to improve plant defense response against fungal pathogens

DOEpatents

Wan, Jinrong; Stacey, Gary; Stacey, Minviluz; Zhang, Xuecheng

2013-10-15

Perception of chitin fragments (chitooligosaccharides) is an important first step in plant defense response against fungal pathogen. LysM receptor-like kinases (LysM RLKs) are instrumental in this perception process. LysM RLKs also play a role in activating transcription of chitin-responsive genes (CRGs) in plants. Mutations in the LysM kinase receptor genes or the downstream CRGs may affect the fungal susceptibility of a plant. Mutations in LysM RLKs or transgenes carrying the same may be beneficial in imparting resistance against fungal pathogens.

Starvation and Imidacloprid Exposure Influence Immune Response by Anoplophora glabripennis (Coleoptera: Cerambycidae) to a Fungal Pathogen.

PubMed

Fisher, Joanna J; Castrillo, Louela A; Donzelli, Bruno G G; Hajek, Ann E

2017-08-01

In several insect systems, fungal entomopathogens synergize with neonicotinoid insecticides which results in accelerated host death. Using the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), an invasive woodborer inadvertently introduced into North America and Europe, we investigated potential mechanisms in the synergy between the entomopathogenic fungus Metarhizium brunneum Petch and the insecticide imidacloprid. A potential mechanism underlying this synergy could be imidacloprid's ability to prevent feeding shortly after administration. We investigated whether starvation would have an impact similar to imidacloprid exposure on the mortality of fungal-inoculated beetles. Using real-time PCR to quantify fungal load in inoculated beetles, we determined how starvation and pesticide exposure impacted beetles' ability to tolerate or resist a fungal infection. The effect of starvation and pesticide exposure on the encapsulation and melanization immune responses of the beetles was also quantified. Starvation had a similar impact on the survival of M. brunneum-inoculated beetles compared to imidacloprid exposure. The synergy, however, was not completely due to starvation, as imidacloprid reduced the beetles' melanotic encapsulation response and capsule area, while starvation did not significantly reduce these immune responses. Our results suggest that there are multiple interacting mechanisms involved in the synergy between M. brunneum and imidacloprid. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

PubMed Central

Schleiss, Mark R.

2013-01-01

Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus. Areas for potential development of novel therapeutic intervention are suggested for improving the outcome of this disabling congenital infection. PMID:21827434

Defense-related proteins involved in sugarcane responses to biotic stress

PubMed Central

Souza, Thais P.; Dias, Renata O.; Silva-Filho, Marcio C.

2017-01-01

Abstract Sugarcane is one of the most important agricultural crops in the world. However, pathogen infection and herbivore attack cause constant losses in yield. Plants respond to pathogen infection by inducing the expression of several protein types, such as glucanases, chitinases, thaumatins, peptidase inhibitors, defensins, catalases and glycoproteins. Proteins induced by pathogenesis are directly or indirectly involved in plant defense, leading to pathogen death or inducing other plant defense responses. Several of these proteins are induced in sugarcane by different pathogens or insects and have antifungal or insecticidal activity. In this review, defense-related proteins in sugarcane are described, with their putative mechanisms of action, pathogen targets and biotechnological perspectives. PMID:28222203

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).

Insights into molecular and metabolic events associated with fruit response to post-harvest fungal pathogens

PubMed Central

Alkan, Noam; Fortes, Ana M.

2015-01-01

Due to post-harvest losses more than 30% of harvested fruits will not reach the consumers’ plate. Fungal pathogens play a key role in those losses, as they cause most of the fruit rots and the customer complaints. Many of the fungal pathogens are already present in the unripe fruit but remain quiescent during fruit growth until a particular phase of fruit ripening and senescence. The pathogens sense the developmental change and switch into the devastating necrotrophic life style that causes fruit rotting. Colonization of unripe fruit by the fungus initiates defensive responses that limit fungal growth and development. However, during fruit ripening several physiological processes occur that correlate with increased fruit susceptibility. In contrast to plant defenses in unripe fruit, the defense posture of ripe fruit entails a different subset of defense responses that will end with fruit rotting and losses. This review will focus on several aspects of molecular and metabolic events associated with fleshy fruit responses induced by post-harvest fungal pathogens during fruit ripening. PMID:26539204

The role of the plasma membrane H+-ATPase in plant-microbe interactions.

PubMed

Elmore, James Mitch; Coaker, Gitta

2011-05-01

Plasma membrane (PM) H+-ATPases are the primary pumps responsible for the establishment of cellular membrane potential in plants. In addition to regulating basic aspects of plant cell function, these enzymes contribute to signaling events in response to diverse environmental stimuli. Here, we focus on the roles of the PM H+-ATPase during plant-pathogen interactions. PM H+-ATPases are dynamically regulated during plant immune responses and recent quantitative proteomics studies suggest complex spatial and temporal modulation of PM H+-ATPase activity during early pathogen recognition events. Additional data indicate that PM H+-ATPases cooperate with the plant immune signaling protein RIN4 to regulate stomatal apertures during bacterial invasion of leaf tissue. Furthermore, pathogens have evolved mechanisms to manipulate PM H+-ATPase activity during infection. Thus, these ubiquitous plant enzymes contribute to plant immune responses and are targeted by pathogens to increase plant susceptibility.

Dynamics of T cell, antigen-presenting cell, and pathogen interactions during recall responses in the lymph node.

PubMed

Chtanova, Tatyana; Han, Seong-Ji; Schaeffer, Marie; van Dooren, Giel G; Herzmark, Paul; Striepen, Boris; Robey, Ellen A

2009-08-21

Memory T cells circulate through lymph nodes where they are poised to respond rapidly upon re-exposure to a pathogen; however, the dynamics of memory T cell, antigen-presenting cell, and pathogen interactions during recall responses are largely unknown. We used a mouse model of infection with the intracellular protozoan parasite, Toxoplasma gondii, in conjunction with two-photon microscopy, to address this question. After challenge, memory T cells migrated more rapidly than naive T cells, relocalized toward the subcapsular sinus (SCS) near invaded macrophages, and engaged in prolonged interactions with infected cells. Parasite invasion of T cells occurred by direct transfer of the parasite from the target cell into the T cell and corresponded to an antigen-specific increase in the rate of T cell invasion. Our results provide insight into cellular interactions during recall responses and suggest a mechanism of pathogen subversion of the immune response.

Proteome and Secretome Analysis Reveals Differential Post-transcriptional Regulation of Toll-like Receptor Responses*

PubMed Central

Koppenol-Raab, Marijke; Sjoelund, Virginie; Manes, Nathan P.; Gottschalk, Rachel A.; Dutta, Bhaskar; Benet, Zachary L.; Fraser, Iain D. C.

2017-01-01

The innate immune system is the organism's first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. PMID:28235783

Forest health in a changing world: Effects of globalization and climate change on forest insect and pathogen impacts

Treesearch

T. D. Ramsfield; Barbara Bentz; M. Faccoli; H. Jactel; E. G. Brockerhoff

2016-01-01

Forests and trees throughout the world are increasingly affected by factors related to global change. Expanding international trade has facilitated invasions of numerous insects and pathogens into new regions. Many of these invasions have caused substantial forest damage, economic impacts and losses of ecosystem goods and services provided by trees. Climate...

Comparative genomics of a plant-pathogenic fungus, Pyrenophora tritici-repentis, reveals transduplication and the impact of repeat elements on pathogenicity and population divergence. G3-Genes, Genomes, Genetics.

USDA-ARS?s Scientific Manuscript database

Pyrenophora tritici-repentis is a necrotrophic fungal pathogen and causal agent of tan spot disease of wheat, which has increased significantly over the last few decades. Pathogenicity by this fungus is due to host-selective toxins. These toxins are recognized by their host plant in a genotype-speci...

Pathogenomics: an updated European Research Agenda.

PubMed

Demuth, Andreas; Aharonowitz, Yair; Bachmann, Till T; Blum-Oehler, Gabriele; Buchrieser, Carmen; Covacci, Antonello; Dobrindt, Ulrich; Emödy, Levente; van der Ende, Arie; Ewbank, Jonathan; Fernández, Luis Angel; Frosch, Matthias; García-Del Portillo, Francisco; Gilmore, Michael S; Glaser, Philippe; Goebel, Werner; Hasnain, Seyed E; Heesemann, Jürgen; Islam, Khalid; Korhonen, Timo; Maiden, Martin; Meyer, Thomas F; Montecucco, Cesare; Oswald, Eric; Parkhill, Julian; Pucciarelli, M Graciela; Ron, Eliora; Svanborg, Catharina; Uhlin, Bernt Eric; Wai, Sun Nyunt; Wehland, Jürgen; Hacker, Jörg

2008-05-01

The emerging genomic technologies and bioinformatics provide novel opportunities for studying life-threatening human pathogens and to develop new applications for the improvement of human and animal health and the prevention, treatment, and diagnosis of infections. Based on the ecology and population biology of pathogens and related organisms and their connection to epidemiology, more accurate typing technologies and approaches will lead to better means of disease control. The analysis of the genome plasticity and gene pools of pathogenic bacteria including antigenic diversity and antigenic variation results in more effective vaccines and vaccine implementation programs. The study of newly identified and uncultivated microorganisms enables the identification of new threats. The scrutiny of the metabolism of the pathogen in the host allows the identification of new targets for anti-infectives and therapeutic approaches. The development of modulators of host responses and mediators of host damage will be facilitated by the research on interactions of microbes and hosts, including mechanisms of host damage, acute and chronic relationships as well as commensalisms. The study of multiple pathogenic and non-pathogenic microbes interacting in the host will improve the management of multiple infections and will allow probiotic and prebiotic interventions. Needless to iterate, the application of the results of improved prevention and treatment of infections into clinical tests will have a positive impact on the management of human and animal disease. The Pathogenomics Research Agenda draws on discussions with experts of the Network of Excellence "EuroPathoGenomics" at the management board meeting of the project held during 18-21 April 2007, in the Villa Vigoni, Menaggio, Italy. Based on a proposed European Research Agenda in the field of pathogenomics by the ERA-NET PathoGenoMics the meeting's participants updated the established list of topics as the research agenda for the future.

Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea

PubMed Central

Tickell, Kirkby D.; Pavlinac, Patricia B.; John-Stewart, Grace C.; Denno, Donna M.; Richardson, Barbra A.; Naulikha, Jaqueline M.; Kirera, Ronald K.; Swierczewski, Brett E.; Singa, Benson O.; Walson, Judd L.

2017-01-01

Abstract. Children with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6–59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ −2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% CI: 1.5 to 3.8, P < 0.01), and enteroaggregative Escherichia coli recovered from their stool (aPR: 1.8, 1.1–2.8, P = 0.02). There were no differences in the prevalence of other pathogens by wasting status after confounder adjustment. Stunting was not associated with clinical severity or the presence of specific pathogens. Wasted children with diarrhea presented with more severe disease than children without malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children. PMID:29140236

Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea.

PubMed

Tickell, Kirkby D; Pavlinac, Patricia B; John-Stewart, Grace C; Denno, Donna M; Richardson, Barbra A; Naulikha, Jaqueline M; Kirera, Ronald K; Swierczewski, Brett E; Singa, Benson O; Walson, Judd L

2017-11-01

Children with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6-59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ -2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% CI: 1.5 to 3.8, P < 0.01), and enteroaggregative Escherichia coli recovered from their stool (aPR: 1.8, 1.1-2.8, P = 0.02). There were no differences in the prevalence of other pathogens by wasting status after confounder adjustment. Stunting was not associated with clinical severity or the presence of specific pathogens. Wasted children with diarrhea presented with more severe disease than children without malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children.

The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

PubMed Central

Dalluge, Joseph J.; Welchlin, Cole W.; Hughes, John; Han, Wei; Blackwell, Timothy S.; Laguna, Theresa A.; Williams, Bryan J.

2014-01-01

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic. PMID:25350753

The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung.

PubMed

Paulson, Nick B; Gilbertsen, Adam J; Dalluge, Joseph J; Welchlin, Cole W; Hughes, John; Han, Wei; Blackwell, Timothy S; Laguna, Theresa A; Williams, Bryan J

2014-01-01

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic.

Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys.

PubMed

Chan, Ming Liang; Petravic, Janka; Ortiz, Alexandra M; Engram, Jessica; Paiardini, Mirko; Cromer, Deborah; Silvestri, Guido; Davenport, Miles P

2010-12-22

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, 'natural hosts' of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to 'fuel the fire' of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection.

Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys

PubMed Central

Chan, Ming Liang; Petravic, Janka; Ortiz, Alexandra M.; Engram, Jessica; Paiardini, Mirko; Cromer, Deborah; Silvestri, Guido; Davenport, Miles P.

2010-01-01

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, ‘natural hosts’ of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to ‘fuel the fire’ of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection. PMID:20591864

Environmental Factors and Zoonotic Pathogen Ecology in Urban Exploiter Species.

PubMed

Rothenburger, Jamie L; Himsworth, Chelsea H; Nemeth, Nicole M; Pearl, David L; Jardine, Claire M

2017-09-01

Knowledge of pathogen ecology, including the impacts of environmental factors on pathogen and host dynamics, is essential for determining the risk that zoonotic pathogens pose to people. This review synthesizes the scientific literature on environmental factors that influence the ecology and epidemiology of zoonotic microparasites (bacteria, viruses and protozoa) in globally invasive urban exploiter wildlife species (i.e., rock doves [Columba livia domestica], European starlings [Sturnus vulgaris], house sparrows [Passer domesticus], Norway rats [Rattus norvegicus], black rats [R. rattus] and house mice [Mus musculus]). Pathogen ecology, including prevalence and pathogen characteristics, is influenced by geographical location, habitat, season and weather. The prevalence of zoonotic pathogens in mice and rats varies markedly over short geographical distances, but tends to be highest in ports, disadvantaged (e.g., low income) and residential areas. Future research should use epidemiological approaches, including random sampling and robust statistical analyses, to evaluate a range of biotic and abiotic environmental factors at spatial scales suitable for host home range sizes. Moving beyond descriptive studies to uncover the causal factors contributing to uneven pathogen distribution among wildlife hosts in urban environments may lead to targeted surveillance and intervention strategies. Application of this knowledge to urban maintenance and planning may reduce the potential impacts of urban wildlife-associated zoonotic diseases on people.

Dietary Supplementation of Honey Bee Larvae with Arginine and Abscisic Acid Enhances Nitric Oxide and Granulocyte Immune Responses after Trauma.

PubMed

Negri, Pedro; Ramirez, Leonor; Quintana, Silvina; Szawarski, Nicolás; Maggi, Matías; Le Conte, Yves; Lamattina, Lorenzo; Eguaras, Martin

2017-08-15

Many biotic and abiotic stressors impact bees' health, acting as immunosupressors and contribute to colony losses. Thus, the importance of studying the immune response of honey bees is central to develop new strategies aiming to enhance bees' fitness to confront the threats affecting them. If a pathogen breaches the physical and chemical barriers, honey bees can protect themselves from infection with cellular and humoral immune responses which represent a second line of defense. Through a series of correlative studies we have previously reported that abscisic acid (ABA) and nitric oxide (NO) share roles in the same immune defenses of Apis mellifera ( A. mellifera ). Here we show results supporting that the supplementation of bee larvae's diet reared in vitro with l-Arginine (precursor of NO) or ABA enhanced the immune activation of the granulocytes in response to wounding and lipopolysaccharide (LPS) injection.

Dietary Supplementation of Honey Bee Larvae with Arginine and Abscisic Acid Enhances Nitric Oxide and Granulocyte Immune Responses after Trauma

PubMed Central

Ramirez, Leonor; Quintana, Silvina; Szawarski, Nicolás; Maggi, Matías; Le Conte, Yves; Lamattina, Lorenzo; Eguaras, Martin

2017-01-01

Many biotic and abiotic stressors impact bees’ health, acting as immunosupressors and contribute to colony losses. Thus, the importance of studying the immune response of honey bees is central to develop new strategies aiming to enhance bees’ fitness to confront the threats affecting them. If a pathogen breaches the physical and chemical barriers, honey bees can protect themselves from infection with cellular and humoral immune responses which represent a second line of defense. Through a series of correlative studies we have previously reported that abscisic acid (ABA) and nitric oxide (NO) share roles in the same immune defenses of Apis mellifera (A. mellifera). Here we show results supporting that the supplementation of bee larvae’s diet reared in vitro with l-Arginine (precursor of NO) or ABA enhanced the immune activation of the granulocytes in response to wounding and lipopolysaccharide (LPS) injection. PMID:28809782

Comparison of the h-Index Scores Among Pathogens Identified as Emerging Hazards in North America.

PubMed

Cox, R; McIntyre, K M; Sanchez, J; Setzkorn, C; Baylis, M; Revie, C W

2016-02-01

Disease surveillance must assess the relative importance of pathogen hazards. Here, we use the Hirsch index (h-index) as a novel method to identify and rank infectious pathogens that are likely to be a hazard to human health in the North American region. This bibliometric index was developed to quantify an individual's scientific research output and was recently used as a proxy measure for pathogen impact. Analysis of more than 3000 infectious organisms indicated that 651 were human pathogen species that had been recorded in the North American region. The h-index of these pathogens ranged from 0 to 584. The h-index of emerging pathogens was greater than non-emerging pathogens as was the h-index of frequently pathogenic pathogens when compared to non-pathogenic pathogens. As expected, the h-index of pathogens varied over time between 1960 and 2011. We discuss how the h-index can contribute to pathogen prioritization and as an indicator of pathogen emergence. © 2014 Blackwell Verlag GmbH.

Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response.

PubMed

Hempstead, Andrew D; Isberg, Ralph R

2015-12-08

Cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. One system that responds to these stimuli is the IRE1 branch of the unfolded protein response (UPR), a sensor of endoplasmic reticulum (ER) stress. Activation of IRE1, in the context of Toll-like receptor (TLR) signaling, induces strong proinflammatory cytokine induction. We show here that Legionella pneumophila, an intravacuolar pathogen that replicates in an ER-associated compartment, blocks activation of the IRE1 pathway despite presenting pathogen products that stimulate this response. L. pneumophila TLR ligands induced the splicing of mRNA encoding XBP1s, the main target of IRE1 activity. L. pneumophila was able to inhibit both chemical and bacterial induction of XBP1 splicing via bacterial translocated proteins that interfere with host protein translation. A strain lacking five translocated translation elongation inhibitors was unable to block XBP1 splicing, but this could be rescued by expression of a single such inhibitor, consistent with limitation of the response by translation elongation inhibitors. Chemical inhibition of translation elongation blocked pattern recognition receptor-mediated XBP1 splicing, mimicking the effects of the bacterial translation inhibitors. In contrast, host cell-promoted inhibition of translation initiation in response to the pathogen was ineffective in blocking XBP1 splicing, demonstrating the need for the elongation inhibitors for protection from the UPR. The inhibition of host translation elongation may be a common strategy used by pathogens to limit the innate immune response by interfering with signaling via the UPR.

Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity.

PubMed

Pryhuber, Gloria S

2015-12-01

Premature infants suffer significant respiratory morbidity during infancy with long-term negative consequences on health, quality of life, and health care costs. Enhanced susceptibility to a variety of infections and inflammation play a large role in early and prolonged lung disease following premature birth, although the mechanisms of susceptibility and immune dysregulation are active areas of research. This article reviews aspects of host-pathogen interactions and immune responses that are altered by preterm birth and that impact chronic respiratory morbidity in these children. Copyright © 2015 Elsevier Inc. All rights reserved.

A plant EPF-type zinc-finger protein, CaPIF1, involved in defence against pathogens.

PubMed

Oh, Sang-Keun; Park, Jeong Mee; Joung, Young Hee; Lee, Sanghyeob; Chung, Eunsook; Kim, Soo-Yong; Yu, Seung Hun; Choi, Doil

2005-05-01

SUMMARY To understand better the defence responses of plants to pathogen attack, we challenged hot pepper plants with bacterial pathogens and identified transcription factor-encoding genes whose expression patterns were altered during the subsequent hypersensitive response. One of these genes, CaPIF1 (Capsicum annuum Pathogen-Induced Factor 1), was characterized further. This gene encodes a plant-specific EPF-type protein that contains two Cys(2)/His(2) zinc fingers. CaPIF1 expression was rapidly and specifically induced when pepper plants were challenged with bacterial pathogens to which they are resistant. In contrast, challenge with a pathogen to which the plants are susceptible only generated weak CaPIF1 expression. CaPIF1 expression was also strongly induced in pepper leaves by the exogenous application of ethephon, an ethylene-releasing compound, and salicylic acid, whereas methyl jasmonate had only moderate effects. CaPIF1 localized to the nuclei of onion epidermis when expressed as a CaPIF1-smGFP fusion protein. Transgenic tobacco plants over-expressing CaPIF1 driven by the CaMV 35S promoter showed increased resistance to challenge with a tobacco-specific pathogen or non-host bacterial pathogens. These plants also showed constitutive up-regulation of multiple defence-related genes. Moreover, virus-induced silencing of the CaPIF1 orthologue in Nicotiana benthamiana enhanced susceptibility to the same host or non-host bacterial pathogens. These observations provide evidence that an EPF-type Cys(2)/His(2) zinc-finger protein plays a crucial role in the activation of the pathogen defence response in plants.

Prebiotics in food animals, a potential to reduce foodborne pathogens and disease

USDA-ARS?s Scientific Manuscript database

Animals can be seriously impacted by bacterial pathogens that affect their growth efficiency and overall health, as well as food safety of animal-derived products. Some pathogenic bacteria, such as Salmonella, can be a shared problem for both human and animal health and can be found in many animal ...

Prebiotics in food animals: A potential to reduce foodborne pathogens and disease

USDA-ARS?s Scientific Manuscript database

Animals can be seriously impacted by bacterial pathogens that affect their growth efficiency and overall health, as well as food safety of animal-derived products. Some pathogenic bacteria, such as Salmonella, can be a shared problem for both human and animal health and can be found in many animal ...

Approaches to understanding the impact of life-history features on plant-pathogen co-evolutionary dynamics

Treesearch

Jeremy J. Burdon; Peter H. Thrall; Adnane Nemri

2012-01-01

Natural plant-pathogen associations are complex interactions in which the interplay of environment, host, and pathogen factors results in spatially heterogeneous ecological and epidemiological dynamics. The evolutionary patterns that result from the interaction of these factors are still relatively poorly understood. Recently, integration of the appropriate spatial and...

Specific Mutations in H5N1 Mainly Impact the Magnitude and Velocity of the Host Response in Mice

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

Tchitchek, Nicholas; Eisfeld, Amie J.; Tisoncik-Go, Jennifer

2013-07-29

Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators is not well-understood. By analyzing a collection of mouse lung samples infected by A/Vietnam/1203/2004 (H5N1; VN1203) influenza, we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that infection concentrations and four specific mutations in VN1203 mainly impact on the magnitude and velocity of the host response kinetics, rather than on specific sets of genes up- and down-regulated. We observed similar kinetic effects usingmore » A/California/04/2009 (H1N1)-infected samples, and we show that these effects correlate with mice morbidity and viral titer measurements. Speed and extent of changes in the host response between days 1 and 2 post-infection were attenuated for each VN1203 mutant compared to the wild-type, except for PB1-F2 deletion at a high dose, which was associated with high virulence. This indicates that the host response in that time frame is critical and that immunomodulatory therapeutics should specifically be applied during the early days post-infection.« less

Effect of antibodies on pathogen dynamics with delays and two routes of infection

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Almatrafi, A. A.; Hobiny, A. D.

2018-06-01

We study the global stability of pathogen dynamics models with saturated pathogen-susceptible and infected-susceptible incidence. The models incorporate antibody immune response and three types of discrete or distributed time delays. We first show that the solutions of the model are nonnegative and ultimately bounded. We determine two threshold parameters, the basic reproduction number and antibody response activation number. We establish the existence and stability of the steady states. We study the global stability analysis of models using Lyapunov method. The numerical simulations have shown that antibodies can reduce the pathogen progression.

The Impact of Recombination Hotspots on Genome Evolution of a Fungal Plant Pathogen.

PubMed

Croll, Daniel; Lendenmann, Mark H; Stewart, Ethan; McDonald, Bruce A

2015-11-01

Recombination has an impact on genome evolution by maintaining chromosomal integrity, affecting the efficacy of selection, and increasing genetic variability in populations. Recombination rates are a key determinant of the coevolutionary dynamics between hosts and their pathogens. Historic recombination events created devastating new pathogens, but the impact of ongoing recombination in sexual pathogens is poorly understood. Many fungal pathogens of plants undergo regular sexual cycles, and sex is considered to be a major factor contributing to virulence. We generated a recombination map at kilobase-scale resolution for the haploid plant pathogenic fungus Zymoseptoria tritici. To account for intraspecific variation in recombination rates, we constructed genetic maps from two independent crosses. We localized a total of 10,287 crossover events in 441 progeny and found that recombination rates were highly heterogeneous within and among chromosomes. Recombination rates on large chromosomes were inversely correlated with chromosome length. Short accessory chromosomes often lacked evidence for crossovers between parental chromosomes. Recombination was concentrated in narrow hotspots that were preferentially located close to telomeres. Hotspots were only partially conserved between the two crosses, suggesting that hotspots are short-lived and may vary according to genomic background. Genes located in hotspot regions were enriched in genes encoding secreted proteins. Population resequencing showed that chromosomal regions with high recombination rates were strongly correlated with regions of low linkage disequilibrium. Hence, genes in pathogen recombination hotspots are likely to evolve faster in natural populations and may represent a greater threat to the host. Copyright © 2015 by the Genetics Society of America.

Pathogen Proliferation Governs the Magnitude but Compromises the Function of CD8 T Cells1

PubMed Central

Sad, Subash; Dudani, Renu; Gurnani, Komal; Russell, Marsha; van Faassen, Henk; Finlay, Brett; Krishnan, Lakshmi

2014-01-01

CD8+ T cell memory is critical for protection against many intracellular pathogens. However, it is not clear how pathogen virulence influences the development and function of CD8+ T cells. Salmonella typhimurium (ST) is an intracellular bacterium that causes rapid fatality in susceptible mice and chronic infection in resistant strains. We have constructed recombinant mutants of ST, expressing the same immunodominant Ag OVA, but defective in various key virulence genes. We show that the magnitude of CD8+ T cell response correlates directly to the intracellular proliferation of ST. Wild-type ST displayed efficient intracellular proliferation and induced increased numbers of OVA-specific CD8+ T cells upon infection in mice. In contrast, mutants with defective Salmonella pathogenicity island II genes displayed poor intracellular proliferation and induced reduced numbers of OVA-specific CD8+ T cells. However, when functionality of the CD8+ T cell response was measured, mutants of ST induced a more functional response compared with the wild-type ST. Infection with wild-type ST, in contrast to mutants defective in pathogenicity island II genes, induced the generation of mainly effector-memory CD8+ T cells that expressed little IL-2, failed to mediate efficient cytotoxicity, and proliferated poorly in response to Ag challenge in vivo. Taken together, these results indicate that pathogens that proliferate rapidly and chronically in vivo may evoke functionally inferior memory CD8+ T cells which may promote the survival of the pathogen. PMID:18424704

Impacts of climate change on indirect human exposure to pathogens and chemicals from agriculture.

PubMed

Boxall, Alistair B A; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D; Haygarth, Philip M; Hutchinson, Thomas; Kovats, R Sari; Leonardi, Giovanni; Levy, Leonard S; Nichols, Gordon; Parsons, Simon A; Potts, Laura; Stone, David; Topp, Edward; Turley, David B; Walsh, Kerry; Wellington, Elizabeth M H; Williams, Richard J

2009-04-01

Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes.

Temporal impact of the vascular wilt pathogen Verticillium dahliae on tomato root proteome.

PubMed

Witzel, Katja; Buhtz, Anja; Grosch, Rita

2017-10-03

The soil-borne fungus Verticillium dahliae is the causal agent of wilting disease and affects a wide range of plant species worldwide. Here, we report on the time-resolved analysis of the tomato root proteome in response to fungal colonization. Tomato (Solanum lycopersicum cv. Hildares) was inoculated with V. dahliae at the two-leaf stage and roots were harvested at 7, 14 and 21 days post inoculation (dpi). In order to identify proteins related to the fungal spread at the different time points, a subsequent proteome analysis by two-dimensional differential gel electrophoresis (2D-DIGE) was conducted on samples from three independent experiments. Hierarchical clustering and k-means clustering of identified proteins distinguished early and late responses to fungal colonization. The results underline that plant defense and adaptation responses are timely coordinated. Proteins involved in oxidative stress were down-regulated at 7 dpi but induced 21 dpi indicating versatile reactive oxygen species signaling interacting with salicylic acid defence signaling at that stage of infection. Drought-stress proteins were induced at 21 dpi, reflecting the beginning of wilting symptoms. Notably, two proteins involved in energy-generating pathways were induced throughout all sampling dates and may reflect the increase in metabolic activity to maintain root growth and, concurrently, activate defense responses. Mounting of defense responses requires a substantial flux of carbon and nitrogen from primary to secondary metabolites. In-depth understanding of these key metabolic pathways required for growth and defense responses, especially at proteome level, will allow the development of breeding strategies for crops where Verticillium tolerance is absent. Our data show early and late responses of tomato root proteins towards pathogen infection and identify primary metabolism enzymes affected by V. dahliae. Those proteins represent candidates for plant improvement. Copyright © 2017 Elsevier B.V. All rights reserved.

Glycomaterials for probing host–pathogen interactions and the immune response

PubMed Central

Huang, Mia L; Fisher, Christopher J

2016-01-01

The initial engagement of host cells by pathogens is often mediated by glycan structures presented on the cell surface. Various components of the glycocalyx can be targeted by pathogens for adhesion to facilitate infection. Glycans also play integral roles in the modulation of the host immune response to infection. Therefore, understanding the parameters that define glycan interactions with both pathogens and the various components of the host immune system can aid in the development of strategies to prevent, interrupt, or manage infection. Glycomaterials provide a unique and powerful tool with which to interrogate the compositional and functional complexity of the glycocalyx. The objective of this review is to highlight some key contributions from this area of research in deciphering the mechanisms of pathogenesis and the associated host response. PMID:27190259

Protein extraction and gel-based separation methods to analyze responses to pathogens in carnation (Dianthus caryophyllus L).

PubMed

Ardila, Harold Duban; Fernández, Raquel González; Higuera, Blanca Ligia; Redondo, Inmaculada; Martínez, Sixta Tulia

2014-01-01

We are currently using a 2-DE-based proteomics approach to study plant responses to pathogenic fungi by using the carnation (Dianthus caryophyllus L)-Fusarium oxysporum f. sp. dianthi pathosystem. It is clear that the protocols for the first stages of a standard proteomics workflow must be optimized to each biological system and objectives of the research. The optimization procedure for the extraction and separation of proteins by 1-DE and 2-DE in the indicated system is reported. This strategy can be extrapolated to other plant-pathogen interaction systems in order to perform an evaluation of the changes in the host protein profile caused by the pathogen and to identify proteins which, at early stages, are involved or implicated in the plant defense response.

Impacts of an introduced forest pathogen on the risk of Lyme disease in California.

PubMed

Swei, Andrea; Briggs, Cheryl J; Lane, Robert S; Ostfeld, Richard S

2012-08-01

Global changes such as deforestation, climate change, and invasive species have the potential to greatly alter zoonotic disease systems through impacts on biodiversity. This study examined the impact of the invasive pathogen that causes sudden oak death (SOD) on the ecology of Lyme disease in California. The Lyme disease bacterium, Borrelia burgdorferi, is maintained in the far western United States by a suite of animal reservoirs including the dusky-footed woodrat (Neotoma fuscipes) and deer mouse (Peromyscus maniculatus), and is transmitted by the western black-legged tick (Ixodes pacificus). Other vertebrates, such as the western fence lizard (Sceloporus occidentalis), are important tick hosts but are not reservoirs of the pathogen. Previous work found that higher levels of SOD are correlated with greater abundance of P. maniculatus and S. occidentalis and lower N. fuscipes abundance. Here we model the contribution of these tick hosts to Lyme disease risk and also evaluate the potential impact of SOD on infection prevalence of the tick vector. By empirically parameterizing a static model with field and laboratory data on tick hosts, we predict that SOD reduces an important index of disease risk, nymphal infection prevalence, leading to a reduction in Lyme disease risk in certain coastal woodlands. Direct observational analysis of the impact of SOD on nymphal infection prevalence supports these model results. This study underscores the important direct and indirect impacts of invasive plant pathogens on biodiversity, the transmission cycles of zoonotic diseases, and ultimately human health.

Elicitor-induced transcription factors for metabolic reprogramming of secondary metabolism in Medicago truncatula

PubMed Central

Naoumkina, Marina A; He, XianZhi; Dixon, Richard A

2008-01-01

Background Exposure of Medicago truncatula cell suspension cultures to pathogen or wound signals leads to accumulation of various classes of flavonoid and/or triterpene defense molecules, orchestrated via a complex signalling network in which transcription factors (TFs) are essential components. Results In this study, we analyzed TFs responding to yeast elicitor (YE) or methyl jasmonate (MJ). From 502 differentially expressed TFs, WRKY and AP2/EREBP gene families were over-represented among YE-induced genes whereas Basic Helix-Loop-Helix (bHLH) family members were more over-represented among the MJ-induced genes. Jasmonate ZIM-domain (JAZ) transcriptional regulators were highly induced by MJ treatment. To investigate potential involvement of WRKY TFs in signalling, we expressed four Medicago WRKY genes in tobacco. Levels of soluble and wall bound phenolic compounds and lignin were increased in all cases. WRKY W109669 also induced tobacco endo-1,3-β-glucanase (NtPR2) and enhanced the systemic defense response to tobacco mosaic virus in transgenic tobacco plants. Conclusion These results confirm that Medicago WRKY TFs have broad roles in orchestrating metabolic responses to biotic stress, and that they also represent potentially valuable reagents for engineering metabolic changes that impact pathogen resistance. PMID:19102779

Novel approaches are needed to develop tomorrow's antibacterial therapies.

PubMed

Spellberg, Brad; Bartlett, John; Wunderink, Rich; Gilbert, David N

2015-01-15

Society faces a crisis of rising antibiotic resistance even as the pipeline of new antibiotics has been drying up. Antibiotics are a public trust; every individual's use of antibiotics affects their efficacy for everyone else. As such, responses to the antibiotic crisis must take a societal perspective. The market failure of antibiotics is due to a combination of scientific challenges to discovering and developing new antibiotics, unfavorable economics, and a hostile regulatory environment. Scientific solutions include changing the way we screen for new antibiotics. More transformationally, developing new treatments that seek to disarm pathogens without killing them, or that modulate the host inflammatory response to infection, will reduce selective pressure and hence minimize resistance emergence. Economic transformation will require new business models to support antibiotic development. Finally, regulatory reform is needed so that clinical development programs are feasible, rigorous, and clinically relevant. Pulmonary and critical care specialists can have tremendous impact on the continued availability of effective antibiotics. Encouraging use of molecular diagnostic tests to allow pathogen-targeted, narrow-spectrum antibiotic therapy, using short rather than unnecessarily long course therapy, reducing inappropriate antibiotic use for probable viral infections, and reducing infection rates will help preserve the antibiotics we have for future generations.

Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4.

PubMed

Qiu, Zhijuan; Cervantes, Jorge L; Cicek, Basak B; Mukherjee, Subhajit; Venkatesh, Madhukumar; Maher, Leigh A; Salazar, Juan C; Mani, Sridhar; Khanna, Kamal M

2016-08-23

The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr(-/-) mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr(-/-) mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr(-/-) mice. Mechanistically, the heightened inflammation in Pxr(-/-) mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection.

Eosinophils, probiotics, and the microbiome.

PubMed

Rosenberg, Helene F; Masterson, Joanne C; Furuta, Glenn T

2016-11-01

There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored. © Society for Leukocyte Biology.

Evaluation of chlorpyrifos effects, alone and combined with lipopolysaccharide stress, on DNA integrity and immune responses of the three-spined stickleback, Gasterosteus aculeatus.

PubMed

Marchand, Adrien; Porcher, Jean-Marc; Turies, Cyril; Chadili, Edith; Palluel, Olivier; Baudoin, Patrick; Betoulle, Stéphane; Bado-Nilles, Anne

2017-11-01

Organism immune defences might be weakened by pollutants, largely detected in aquatic ecosystems, leading to the facilitation for opportunistic pathogens to infect organisms. In this context, destabilization of fish non-specific immune parameters and erythrocyte DNA integrity was tested, on a model fish species, the three-spined stickleback (Gasterosteus aculeatus), after exposure to chlorpyrifos (CPF). Alone, pesticide exposure induced a genotoxic potential (chlorpyrifos at 1.75 and 0.88µg/L) in addition to a decrease in phagocytosis capacity and a stimulation of respiratory burst. Then, to mimic pathogenic infection, fish exposure to chlorpyrifos was combined with lipopolysaccharides (LPS) stress. In this second experiment, an increase of DNA damage was observed in fish exposed to a lower concentration of chlorpyrifos and LPS. Moreover, at the higher concentration of chlorpyrifos, an early destabilization of innate immunity was observed as suggested by the absence of an increase of lysosomal presence in fish injected with LPS. This study highlighted the usefulness of stress on stress responses to better understand the impact of contaminants on the organism's health. Copyright © 2017 Elsevier Inc. All rights reserved.

Centrality in the host-pathogen interactome is associated with pathogen fitness during infection.

PubMed

Crua Asensio, Núria; Muñoz Giner, Elisabet; de Groot, Natalia Sánchez; Torrent Burgas, Marc

2017-01-16

To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host-pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host-pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host-pathogen interactome should be explored as promising targets for antimicrobial drug design.

Centrality in the host-pathogen interactome is associated with pathogen fitness during infection

NASA Astrophysics Data System (ADS)

Crua Asensio, Núria; Muñoz Giner, Elisabet; de Groot, Natalia Sánchez; Torrent Burgas, Marc

2017-01-01

To perform their functions proteins must interact with each other, but how these interactions influence bacterial infection remains elusive. Here we demonstrate that connectivity in the host-pathogen interactome is directly related to pathogen fitness during infection. Using Y. pestis as a model organism, we show that the centrality-lethality rule holds for pathogen fitness during infection but only when the host-pathogen interactome is considered. Our results suggest that the importance of pathogen proteins during infection is directly related to their number of interactions with the host. We also show that pathogen proteins causing an extensive rewiring of the host interactome have a higher impact in pathogen fitness during infection. Hence, we conclude that hubs in the host-pathogen interactome should be explored as promising targets for antimicrobial drug design.

Differences in pathogenicity, response to vaccination, and innate immune responses in different types of ducks infected with a virulent H5N1 highly pathogenic avian influenza virus from Vietnam

USDA-ARS?s Scientific Manuscript database

Wild ducks are reservoirs of avian influenza viruses in nature, and usually don’t show signs of disease. However, some Asian lineage H5N1 highly pathogenic avian influenza (HPAI) viruses can cause disease and death in both wild and domestic ducks. The objective of this study was to compare the cli...

Utilizing virus-induced gene silencing for the functional characterization of maize genes during infection with the fungal pathogen Ustilago maydis.

PubMed

van der Linde, Karina; Doehlemann, Gunther

2013-01-01

While in dicotyledonous plants virus-induced gene silencing (VIGS) is well established to study plant-pathogen interaction, in monocots only few examples of efficient VIGS have been reported so far. One of the available systems is based on the brome mosaic virus (BMV) which allows gene silencing in different cereals including barley (Hordeum vulgare), wheat (Triticum aestivum), and maize (Zea mays).Infection of maize plants by the corn smut fungus Ustilago maydis leads to the formation of large tumors on stem, leaves, and inflorescences. During this biotrophic interaction, plant defense responses are actively suppressed by the pathogen, and previous transcriptome analyses of infected maize plants showed comprehensive and stage-specific changes in host gene expression during disease progression.To identify maize genes that are functionally involved in the interaction with U. maydis, we adapted a VIGS system based on the Brome mosaic virus (BMV) to maize at conditions that allow successful U. maydis infection of BMV pre-infected maize plants. This setup enables quantification of VIGS and its impact on U. maydis infection using a quantitative real-time PCR (q(RT)-PCR)-based readout.

Local and Long-Distance Calling: Conversations between the Gut Microbiota and Intra- and Extra-Gastrointestinal Tract Infections.

PubMed

Denny, Joshua E; Powell, Whitney L; Schmidt, Nathan W

2016-01-01

Preservation of health from infectious diseases depends upon both mucosal and systemic immunity via the collaborative effort of innate and adaptive immune responses. The proficiency of host immunity stems from robust defense mechanisms--physical barriers and specialized immune cells--and a failure of these mechanisms leads to pathology. Intriguingly, immunocompetence to pathogens can be shaped by the gut microbiome as recent publications highlight a dynamic interplay between the gut microbiome and host susceptibility to infection. Modulation of host immunity to enteric pathogens has long been studied where gut bacteria shape multiple facts of both innate and adaptive immunity. Conversely, the impact of gut commensals on host immunity to extra-gastrointestinal (GI) tract infections has only recently been recognized. In this context, the gut microbiome can augment host immunity to extra-GI tract bacterial, viral, and parasitic pathogens. This review explores the research that affords insight into the role of the gut microbiome in various infectious diseases, with a particular emphasis on extra-GI tract infections. A better understanding of the link between the gut microbiome and infectious disease will be critical for improving global health in the years ahead.

Zinc stress induces copper depletion in Acinetobacter baumannii.

PubMed

Hassan, Karl A; Pederick, Victoria G; Elbourne, Liam D H; Paulsen, Ian T; Paton, James C; McDevitt, Christopher A; Eijkelkamp, Bart A

2017-03-11

The first row transition metal ions zinc and copper are essential to the survival of many organisms, although in excess these ions are associated with significant toxicity. Here, we examined the impact of zinc and copper stress on Acinetobacter baumannii, a common opportunistic pathogen. We show that extracellular zinc stress induces a copper-specific depletion phenotype in A. baumannii ATCC 17978. Supplementation with copper not only fails to rescue this phenotype, but further exacerbates the copper depletion. Extensive analysis of the A. baumannii ATCC 17978 genome identified 13 putative zinc/copper resistance efflux pumps. Transcriptional analyses show that four of these transporters are responsive to zinc stress, five to copper stress and seven to the combination of zinc and copper stress, thereby revealing a likely foundation for the zinc-induced copper starvation in A. baumannii. In addition, we show that zinc and copper play crucial roles in management of oxidative stress and the membrane composition of A. baumannii. Further, we reveal that zinc and copper play distinct roles in macrophage-mediated killing of this pathogen. Collectively, this study supports the targeting of metal ion homeostatic mechanisms as an effective antimicrobial strategy against multi-drug resistant bacterial pathogens.

Innate and adaptive immune responses in migrating spring-run adult chinook salmon, Oncorhynchus tshawytscha

USGS Publications Warehouse

Dolan, Brian P.; Fisher, Kathleen M.; Colvin, Michael E.; Benda, Susan E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

2016-01-01

Adult Chinook salmon (Oncorhynchus tshawytscha) migrate from salt water to freshwater streams to spawn. Immune responses in migrating adult salmon are thought to diminish in the run up to spawning, though the exact mechanisms for diminished immune responses remain unknown. Here we examine both adaptive and innate immune responses as well as pathogen burdens in migrating adult Chinook salmon in the Upper Willamette River basin. Messenger RNA transcripts encoding antibody heavy chain molecules slightly diminish as a function of time, but are still present even after fish have successfully spawned. In contrast, the innate anti-bacterial effector proteins present in fish plasma rapidly decrease as spawning approaches. Fish also were examined for the presence and severity of eight different pathogens in different organs. While pathogen burden tended to increase during the migration, no specific pathogen signature was associated with diminished immune responses. Transcript levels of the immunosuppressive cytokines IL-10 and TGF beta were measured and did not change during the migration. These results suggest that loss of immune functions in adult migrating salmon are not due to pathogen infection or cytokine-mediated immune suppression, but is rather part of the life history of Chinook salmon likely induced by diminished energy reserves or hormonal changes which accompany spawning.

Ethylene and 1-Aminocyclopropane-1-carboxylate (ACC) in Plant–Bacterial Interactions

PubMed Central

Nascimento, Francisco X.; Rossi, Márcio J.; Glick, Bernard R.

2018-01-01

Ethylene and its precursor 1-aminocyclopropane-1-carboxylate (ACC) actively participate in plant developmental, defense and symbiotic programs. In this sense, ethylene and ACC play a central role in the regulation of bacterial colonization (rhizospheric, endophytic, and phyllospheric) by the modulation of plant immune responses and symbiotic programs, as well as by modulating several developmental processes, such as root elongation. Plant-associated bacterial communities impact plant growth and development, both negatively (pathogens) and positively (plant-growth promoting and symbiotic bacteria). Some members of the plant-associated bacterial community possess the ability to modulate plant ACC and ethylene levels and, subsequently, modify plant defense responses, symbiotic programs and overall plant development. In this work, we review and discuss the role of ethylene and ACC in several aspects of plant-bacterial interactions. Understanding the impact of ethylene and ACC in both the plant host and its associated bacterial community is key to the development of new strategies aimed at increased plant growth and protection. PMID:29520283

Impact of myxomatosis in relation to local persistence in wild rabbit populations: the role of waning immunity and the reproductive period.

PubMed

Fouchet, David; Guitton, Jean-Sébastien; Marchandeau, Stéphane; Pontier, Dominique

2008-02-21

Many diseases are less severe when they are contracted in early life. For highly lethal diseases, such as myxomatosis in rabbits, getting infected early in life can represent the best chance for an individual to survive the disease. For myxomatosis, early infections are attenuated by maternal antibodies. This may lead to the immunisation of the host, preventing the subsequent development of the lethal form of the disease. But early infection of young individuals requires specific demographic and epidemiological contexts, such as a high transmission rate of the pathogen agent. To investigate other factors involved in the impact of such diseases, we have built a stochastic model of a rabbit metapopulation infected by myxomatosis. We show that the impact of the pathogen agent can be reduced by early infections only when the agent has a long local persistence time and/or when the host subpopulations are highly connected. The length of the reproductive period and the duration of acquired immunity are also important factors influencing the persistence of the pathogen and thus, the impact of the disease. Besides confirming the role of classical factors in the persistence of a pathogen agent, such as the size of the subpopulation or the degree of connectivity, our results highlight novel factors that can modulate the impact of diseases whose severity increase with age.

H7N9 and Other Pathogenic Avian Influenza Viruses Elicit a Three-Pronged Transcriptomic Signature That Is Reminiscent of 1918 Influenza Virus and Is Associated with Lethal Outcome in Mice

PubMed Central

Morrison, Juliet; Josset, Laurence; Tchitchek, Nicolas; Chang, Jean; Belser, Jessica A.; Swayne, David E.; Pantin-Jackwood, Mary J.; Tumpey, Terrence M.

2014-01-01

ABSTRACT Modulating the host response is a promising approach to treating influenza, caused by a virus whose pathogenesis is determined in part by the reaction it elicits within the host. Though the pathogenicity of emerging H7N9 influenza virus in several animal models has been reported, these studies have not included a detailed characterization of the host response following infection. Therefore, we characterized the transcriptomic response of BALB/c mice infected with H7N9 (A/Anhui/01/2013) virus and compared it to the responses induced by H5N1 (A/Vietnam/1203/2004), H7N7 (A/Netherlands/219/2003), and pandemic 2009 H1N1 (A/Mexico/4482/2009) influenza viruses. We found that responses to the H7 subtype viruses were intermediate to those elicited by H5N1 and pdm09H1N1 early in infection but that they evolved to resemble the H5N1 response as infection progressed. H5N1, H7N7, and H7N9 viruses were pathogenic in mice, and this pathogenicity correlated with increased transcription of cytokine response genes and decreased transcription of lipid metabolism and coagulation signaling genes. This three-pronged transcriptomic signature was observed in mice infected with pathogenic H1N1 strains such as the 1918 virus, indicating that it may be predictive of pathogenicity across multiple influenza virus strains. Finally, we used host transcriptomic profiling to computationally predict drugs that reverse the host response to H7N9 infection, and we identified six FDA-approved drugs that could potentially be repurposed to treat H7N9 and other pathogenic influenza viruses. IMPORTANCE Emerging avian influenza viruses are of global concern because the human population is immunologically naive to them. Current influenza drugs target viral molecules, but the high mutation rate of influenza viruses eventually leads to the development of antiviral resistance. As the host evolves far more slowly than the virus, and influenza pathogenesis is determined in part by the host response, targeting the host response is a promising approach to treating influenza. Here we characterize the host transcriptomic response to emerging H7N9 influenza virus and compare it with the responses to H7N7, H5N1, and pdm09H1N1. All three avian viruses were pathogenic in mice and elicited a transcriptomic signature that also occurs in response to the legendary 1918 influenza virus. Our work identifies host responses that could be targeted to treat severe H7N9 influenza and identifies six FDA-approved drugs that could potentially be repurposed as H7N9 influenza therapeutics. PMID:24991006

H7N9 and other pathogenic avian influenza viruses elicit a three-pronged transcriptomic signature that is reminiscent of 1918 influenza virus and is associated with lethal outcome in mice.

PubMed

Morrison, Juliet; Josset, Laurence; Tchitchek, Nicolas; Chang, Jean; Belser, Jessica A; Swayne, David E; Pantin-Jackwood, Mary J; Tumpey, Terrence M; Katze, Michael G

2014-09-01

Modulating the host response is a promising approach to treating influenza, caused by a virus whose pathogenesis is determined in part by the reaction it elicits within the host. Though the pathogenicity of emerging H7N9 influenza virus in several animal models has been reported, these studies have not included a detailed characterization of the host response following infection. Therefore, we characterized the transcriptomic response of BALB/c mice infected with H7N9 (A/Anhui/01/2013) virus and compared it to the responses induced by H5N1 (A/Vietnam/1203/2004), H7N7 (A/Netherlands/219/2003), and pandemic 2009 H1N1 (A/Mexico/4482/2009) influenza viruses. We found that responses to the H7 subtype viruses were intermediate to those elicited by H5N1 and pdm09H1N1 early in infection but that they evolved to resemble the H5N1 response as infection progressed. H5N1, H7N7, and H7N9 viruses were pathogenic in mice, and this pathogenicity correlated with increased transcription of cytokine response genes and decreased transcription of lipid metabolism and coagulation signaling genes. This three-pronged transcriptomic signature was observed in mice infected with pathogenic H1N1 strains such as the 1918 virus, indicating that it may be predictive of pathogenicity across multiple influenza virus strains. Finally, we used host transcriptomic profiling to computationally predict drugs that reverse the host response to H7N9 infection, and we identified six FDA-approved drugs that could potentially be repurposed to treat H7N9 and other pathogenic influenza viruses. Emerging avian influenza viruses are of global concern because the human population is immunologically naive to them. Current influenza drugs target viral molecules, but the high mutation rate of influenza viruses eventually leads to the development of antiviral resistance. As the host evolves far more slowly than the virus, and influenza pathogenesis is determined in part by the host response, targeting the host response is a promising approach to treating influenza. Here we characterize the host transcriptomic response to emerging H7N9 influenza virus and compare it with the responses to H7N7, H5N1, and pdm09H1N1. All three avian viruses were pathogenic in mice and elicited a transcriptomic signature that also occurs in response to the legendary 1918 influenza virus. Our work identifies host responses that could be targeted to treat severe H7N9 influenza and identifies six FDA-approved drugs that could potentially be repurposed as H7N9 influenza therapeutics. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Disease-emergence dynamics and control in a socially-structured wildlife species

NASA Astrophysics Data System (ADS)

Pepin, Kim M.; Vercauteren, Kurt C.

2016-04-01

Once a pathogen is introduced in a population, key factors governing rate of spread include contact structure, supply of susceptible individuals and pathogen life-history. We examined the interplay of these factors on emergence dynamics and efficacy of disease prevention and response. We contrasted transmission dynamics of livestock viruses with different life-histories in hypothetical populations of feral swine with different contact structures (homogenous, metapopulation, spatial and network). Persistence probability was near 0 for the FMDV-like case under a wide range of parameter values and contact structures, while persistence was probable for the CSFV-like case. There were no sets of conditions where the FMDV-like pathogen persisted in every stochastic simulation. Even when population growth rates were up to 300% annually, the FMDV-like pathogen persisted in <25% of simulations regardless of transmission probabilities and contact structure. For networks and spatial contact structure, persistence probability of the FMDV-like pathogen was always <10%. Because of its low persistence probability, even very early response to the FMDV-like pathogen in feral swine was unwarranted while response to the CSFV-like pathogen was generally effective. When pre-emergence culling of feral swine caused population declines, it was effective at decreasing outbreak size of both diseases by ≥80%.

The Use of Expert Opinion to Assess the Risk of Emergence or Re-Emergence of Infectious Diseases in Canada Associated with Climate Change

PubMed Central

Cox, Ruth; Revie, Crawford W.; Sanchez, Javier

2012-01-01

Global climate change is predicted to lead to an increase in infectious disease outbreaks. Reliable surveillance for diseases that are most likely to emerge is required, and given limited resources, policy decision makers need rational methods with which to prioritise pathogen threats. Here expert opinion was collected to determine what criteria could be used to prioritise diseases according to the likelihood of emergence in response to climate change and according to their impact. We identified a total of 40 criteria that might be used for this purpose in the Canadian context. The opinion of 64 experts from academic, government and independent backgrounds was collected to determine the importance of the criteria. A weight was calculated for each criterion based on the expert opinion. The five that were considered most influential on disease emergence or impact were: potential economic impact, severity of disease in the general human population, human case fatality rate, the type of climate that the pathogen can tolerate and the current climatic conditions in Canada. There was effective consensus about the influence of some criteria among participants, while for others there was considerable variation. The specific climate criteria that were most likely to influence disease emergence were: an annual increase in temperature, an increase in summer temperature, an increase in summer precipitation and to a lesser extent an increase in winter temperature. These climate variables were considered to be most influential on vector-borne diseases and on food and water-borne diseases. Opinion about the influence of climate on air-borne diseases and diseases spread by direct/indirect contact were more variable. The impact of emerging diseases on the human population was deemed more important than the impact on animal populations. PMID:22848536

Detection of Pathogen Exposure in African Buffalo Using Non-Specific Markers of Inflammation

PubMed Central

Glidden, Caroline K.; Beechler, Brianna; Buss, Peter Erik; Charleston, Bryan; de Klerk-Lorist, Lin-Mari; Maree, Francois Frederick; Muller, Timothy; Pérez-Martin, Eva; Scott, Katherine Anne; van Schalkwyk, Ockert Louis; Jolles, Anna

2018-01-01

Detecting exposure to new or emerging pathogens is a critical challenge to protecting human, domestic animal, and wildlife health. Yet, current techniques to detect infections typically target known pathogens of humans or economically important animals. In the face of the current surge in infectious disease emergence, non-specific disease surveillance tools are urgently needed. Tracking common host immune responses indicative of recent infection may have potential as a non-specific diagnostic approach for disease surveillance. The challenge to immunologists is to identify the most promising markers, which ideally should be highly conserved across pathogens and host species, become upregulated rapidly and consistently in response to pathogen invasion, and remain elevated beyond clearance of infection. This study combined an infection experiment and a longitudinal observational study to evaluate the utility of non-specific markers of inflammation [NSMI; two acute phase proteins (haptoglobin and serum amyloid A), two pro-inflammatory cytokines (IFNγ and TNF-α)] as indicators of pathogen exposure in a wild mammalian species, African buffalo (Syncerus caffer). Specifically, in the experimental study, we asked (1) How quickly do buffalo mount NSMI responses upon challenge with an endemic pathogen, foot-and-mouth disease virus; (2) for how long do NSMI remain elevated after viral clearance and; (3) how pronounced is the difference between peak NSMI concentration and baseline NSMI concentration? In the longitudinal study, we asked (4) Are elevated NSMI associated with recent exposure to a suite of bacterial and viral respiratory pathogens in a wild population? Among the four NSMI that we tested, haptoglobin showed the strongest potential as a surveillance marker in African buffalo: concentrations quickly and consistently reached high levels in response to experimental infection, remaining elevated for almost a month. Moreover, elevated haptoglobin was indicative of recent exposure to two respiratory pathogens assessed in the longitudinal study. We hope this work motivates studies investigating suites of NSMI as indicators for pathogen exposure in a broader range of both pathogen and host species, potentially transforming how we track disease burden in natural populations. PMID:29375568

Concurrent Drought Stress and Vascular Pathogen Infection Induce Common and Distinct Transcriptomic Responses in Chickpea

PubMed Central

Sinha, Ranjita; Gupta, Aarti; Senthil-Kumar, Muthappa

2017-01-01

Chickpea (Cicer arietinum); the second largest legume grown worldwide is prone to drought and various pathogen infections. These drought and pathogen stresses often occur concurrently in the field conditions. However, the molecular events in response to that are largely unknown. The present study examines the transcriptome dynamics in chickpea plants exposed to a combination of water-deficit stress and Ralstonia solanacearum infection. R. solanacearum is a potential wilt disease causing pathogen in chickpea. Drought stressed chickpea plants were infected with this pathogen and the plants were allowed to experience progressive drought with 2 and 4 days of R. solanacearum infection called short duration stress (SD stresses) and long duration stress (LD stresses), respectively. Our study showed that R. solanacearum multiplication decreased under SD-combined stress compared to SD-pathogen but there was no significant change in LD-combined stress compared to LD-pathogen. The microarray analysis during these conditions showed that 821 and 1039 differentially expressed genes (DEGs) were unique to SD- and LD-combined stresses, respectively, when compared with individual stress conditions. Three and fifteen genes were common among all the SD-stress treatments and LD-stress treatments, respectively. Genes involved in secondary cell wall biosynthesis, alkaloid biosynthesis, defense related proteins, and osmo-protectants were up-regulated during combined stress. The expression of genes involved in lignin and cellulose biosynthesis were specifically up-regulated in SD-combined, LD-combined, and LD-pathogen stress. A close transcriptomic association of LD-pathogen stress with SD-combined stress was observed in this study which indicates that R. solanacearum infection also exerts drought stress along with pathogen stress thus mimics combined stress effect. Furthermore the expression profiling of candidate genes using real-time quantitative PCR validated the microarray data. The study showed that down-regulation of defense-related genes during LD-combined stress resulted in an increased bacterial multiplication as compared to SD-combined stress. Overall, our study highlights a sub-set of DEGs uniquely expressed in response to combined stress, which serve as potential candidates for further functional characterization to delineate the molecular response of the plant to concurrent drought-pathogen stress. PMID:28382041

Salicylic acid-mediated establishment of the compatibility between Alternaria brassicicola and Brassica juncea is mitigated by abscisic acid in Sinapis alba.

PubMed

Mazumder, Mrinmoy; Das, Srirupa; Saha, Upala; Chatterjee, Madhuvanti; Bannerjee, Kaushik; Basu, Debabrata

2013-09-01

This work addresses the changes in the phytohormonal signature in the recognition of the necrotrophic fungal pathogen Alternaria brassicicola by susceptible Brassica juncea and resistant Sinapis alba. Although B. juncea, S. alba and Arabidopsis all belong to the same family, Brassicaceae, the phytohormonal response of susceptible B. juncea towards this pathogen is unique because the latter two species express non-host resistance. The differential expression of the PR1 gene and the increased level of salicylic acid (SA) indicated that an SA-mediated biotrophic mode of defence response was triggered in B. juncea upon challenge with the pathogen. Compared to B. juncea, resistant S. alba initiated enhanced abscisic acid (ABA) and jasmonic acid (JA) responses following challenge with this pathogen, as revealed by monitoring the expression of ABA-related genes along with the concentration of ABA and JA. Furthermore, these results were verified by the exogenous application of ABA on B. juncea leaves prior to challenge with A. brassicicola, which resulted in a delayed disease progression, followed by the inhibition of the pathogen-mediated increase in SA response and enhanced JA levels. Therefore, it seems that A. brassicicola is steering the defence response towards a biotrophic mode by mounting an SA response in susceptible B. juncea, whereas the enhanced ABA response of S. alba not only counteracts the SA response but also restores the necrotrophic mode of resistance by enhancing JA biosynthesis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Managing marine disease emergencies in an era of rapid change

PubMed Central

Maynard, Jeffrey; Breyta, Rachel; Carnegie, Ryan B.; Dobson, Andy; Friedman, Carolyn S.; Froelich, Brett; Garren, Melissa; Gulland, Frances M. D.; Heron, Scott F.; Noble, Rachel T.; Revie, Crawford W.; Shields, Jeffrey D.; Vanderstichel, Raphaël; Weil, Ernesto; Wyllie-Echeverria, Sandy; Harvell, C. Drew

2016-01-01

Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. PMID:26880835

Managing marine disease emergencies in an era of rapid change.

PubMed

Groner, Maya L; Maynard, Jeffrey; Breyta, Rachel; Carnegie, Ryan B; Dobson, Andy; Friedman, Carolyn S; Froelich, Brett; Garren, Melissa; Gulland, Frances M D; Heron, Scott F; Noble, Rachel T; Revie, Crawford W; Shields, Jeffrey D; Vanderstichel, Raphaël; Weil, Ernesto; Wyllie-Echeverria, Sandy; Harvell, C Drew

2016-03-05

Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. © 2016 The Author(s).

An overview of molecular stress response mechanisms in Escherichia coli contributing to survival of Shiga toxin-producing Escherichia coli during raw milk cheese production.

PubMed

Peng, Silvio; Tasara, Taurai; Hummerjohann, Jörg; Stephan, Roger

2011-05-01

The ability of foodborne pathogens to survive in certain foods mainly depends on stress response mechanisms. Insight into molecular properties enabling pathogenic bacteria to survive in food is valuable for improvement of the control of pathogens during food processing. Raw milk cheeses are a potential source for human infections with Shiga toxin-producing Escherichia coli (STEC). In this review, we focused on the stress response mechanisms important for allowing STEC to survive raw milk cheese production processes. The major components and regulation pathways for general, acid, osmotic, and heat shock stress responses in E. coli and the implications of these responses for the survival of STEC in raw milk cheeses are discussed.

A method to quantify infectious airborne pathogens at concentrations below the threshold of quantification by culture

PubMed Central

Cutler, Timothy D.; Wang, Chong; Hoff, Steven J.; Zimmerman, Jeffrey J.

2013-01-01

In aerobiology, dose-response studies are used to estimate the risk of infection to a susceptible host presented by exposure to a specific dose of an airborne pathogen. In the research setting, host- and pathogen-specific factors that affect the dose-response continuum can be accounted for by experimental design, but the requirement to precisely determine the dose of infectious pathogen to which the host was exposed is often challenging. By definition, quantification of viable airborne pathogens is based on the culture of micro-organisms, but some airborne pathogens are transmissible at concentrations below the threshold of quantification by culture. In this paper we present an approach to the calculation of exposure dose at microbiologically unquantifiable levels using an application of the “continuous-stirred tank reactor (CSTR) model” and the validation of this approach using rhodamine B dye as a surrogate for aerosolized microbial pathogens in a dynamic aerosol toroid (DAT). PMID:24082399

Enteric pathogens and gut function: role of cytokines and STATs

USDA-ARS?s Scientific Manuscript database

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against pathogens. In response to the invasion of various pathogens, naïve CD4+ cells differenti...

Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.

PubMed

Mortensen, Ninell P; Mercier, Kelly A; McRitchie, Susan; Cavallo, Tammy B; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J

2016-06-01

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 h. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time.

Microfluidics Meets Metabolomics to Reveal the Impact of Campylobacter jejuni Infection on Biochemical Pathways

PubMed Central

Mortensen, Ninell P.; Mercier, Kelly A.; McRitchie, Susan; Cavallo, Tammy B.; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J.

2016-01-01

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 hours. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time. PMID:27231016

High cytokinin levels induce a hypersensitive-like response in tobacco.

PubMed

Novák, Jan; Pavlů, Jaroslav; Novák, Ondřej; Nožková-Hlaváčková, Vladimíra; Špundová, Martina; Hlavinka, Jan; Koukalová, Šárka; Skalák, Jan; Černý, Martin; Brzobohatý, Břetislav

2013-07-01

Cytokinins are positive regulators of shoot development. However, it has previously been demonstrated that efficient activation of the cytokinin biosynthesis gene ipt can cause necrotic lesions and wilting in tobacco leaves. Some plant pathogens reportedly use their ability to produce cytokinins in disease development. In response to pathogen attacks, plants can trigger a hypersensitive response that rapidly kills cells near the infection site, depriving the pathogen of nutrients and preventing its spread. In this study, a diverse set of processes that link ipt activation to necrotic lesion formation were investigated in order to evaluate the potential of cytokinins as signals and/or mediators in plant defence against pathogens. The binary pOp-ipt/LhGR system for dexamethasone-inducible ipt expression was used to increase endogenous cytokinin levels in transgenic tobacco. Changes in the levels of cytokinins and the stress hormones salicylic, jasmonic and abscisic acid following ipt activation were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS). Trends in hydrogen peroxide content and lipid peroxidation were monitored using the potassium iodide and malondialdehyde assays. The subcellular distribution of hydrogen peroxide was investigated using 3,3'-diaminobenzidine staining. The dynamics of transcripts related to photosynthesis and pathogen response were analysed by reverse transcription followed by quantitative PCR. The effects of cytokinins on photosynthesis were deciphered by analysing changes in chlorophyll fluorescence and leaf gas exchange. Plants can produce sufficiently high levels of cytokinins to trigger fast cell death without any intervening chlorosis - a hallmark of the hypersensitive response. The results suggest that chloroplastic hydrogen peroxide orchestrates the molecular responses underpinning the hypersensitive-like response, including the inhibition of photosynthesis, elevated levels of stress hormones, oxidative membrane damage and stomatal closure. Necrotic lesion formation triggered by ipt activation closely resembles the hypersensitive response. Cytokinins may thus act as signals and/or mediators in plant defence against pathogen attack.

Plant pathogen resistance

DOEpatents

Greenberg, Jean T.; Jung, Ho Won; Tschaplinski, Timothy

2015-10-20

Azelaic acid or its derivatives or analogs induce a robust and a speedier defense response against pathogens in plants. Azelaic acid treatment alone does not induce many of the known defense-related genes but activates a plant's defense signaling upon pathogen exposure.

Plant pathogen resistance

DOEpatents

Greenberg, Jean T; Jung, Ho Won; Tschaplinski, Timothy

2012-11-27

Azelaic acid or its derivatives or analogs induce a robust and a speedier defense response against pathogens in plants. Azelaic acid treatment alone does not induce many of the known defense-related genes but activates a plant's defense signaling upon pathogen exposure.

Comparative flight activities and pathogen load of two stocks of honey bees reared in gamma-irradiated combs

USDA-ARS?s Scientific Manuscript database

Gamma irradiation is known to inactivate various pathogens that negatively affect honey bee health. Bee pathogens such as Deformed wing virus (DWV) and Nosema spp. have deleterious impact on foraging activities and bee survival, and have been detected in combs. In this study, we assessed the effects...

Seed diseases and seedborne pathogens of North America

Treesearch

Michelle Cram; Stephen Fraedrich

2010-01-01

Seedborne pathogenic fungi can greatly affect seed quality and cause diseases that impact seedling production in nurseries. Management strategies for the control of various seedborne diseases are based on the epidemiology of the diseases and the biology of the host and pathogen. This paper provides a brief review of seedborne fungal problems that affect conifer seeds...

Plant Responses to Pathogen Attack: Small RNAs in Focus.

PubMed

Islam, Waqar; Noman, Ali; Qasim, Muhammad; Wang, Liande

2018-02-08

Small RNAs (sRNA) are a significant group of gene expression regulators for multiple biological processes in eukaryotes. In plants, many sRNA silencing pathways produce extensive array of sRNAs with specialized roles. The evidence on record advocates for the functions of sRNAs during plant microbe interactions. Host sRNAs are reckoned as mandatory elements of plant defense. sRNAs involved in plant defense processes via different pathways include both short interfering RNA (siRNA) and microRNA (miRNA) that actively regulate immunity in response to pathogenic attack via tackling pathogen-associated molecular patterns (PAMPs) and other effectors. In response to pathogen attack, plants protect themselves with the help of sRNA-dependent immune systems. That sRNA-mediated plant defense responses play a role during infections is an established fact. However, the regulations of several sRNAs still need extensive research. In this review, we discussed the topical advancements and findings relevant to pathogen attack and plant defense mediated by sRNAs. We attempted to point out diverse sRNAs as key defenders in plant systems. It is hoped that sRNAs would be exploited as a mainstream player to achieve food security by tackling different plant diseases.

Plant Responses to Pathogen Attack: Small RNAs in Focus

PubMed Central

2018-01-01

Small RNAs (sRNA) are a significant group of gene expression regulators for multiple biological processes in eukaryotes. In plants, many sRNA silencing pathways produce extensive array of sRNAs with specialized roles. The evidence on record advocates for the functions of sRNAs during plant microbe interactions. Host sRNAs are reckoned as mandatory elements of plant defense. sRNAs involved in plant defense processes via different pathways include both short interfering RNA (siRNA) and microRNA (miRNA) that actively regulate immunity in response to pathogenic attack via tackling pathogen-associated molecular patterns (PAMPs) and other effectors. In response to pathogen attack, plants protect themselves with the help of sRNA-dependent immune systems. That sRNA-mediated plant defense responses play a role during infections is an established fact. However, the regulations of several sRNAs still need extensive research. In this review, we discussed the topical advancements and findings relevant to pathogen attack and plant defense mediated by sRNAs. We attempted to point out diverse sRNAs as key defenders in plant systems. It is hoped that sRNAs would be exploited as a mainstream player to achieve food security by tackling different plant diseases. PMID:29419801

Expression of an Engineered Heterologous Antimicrobial Peptide in Potato Alters Plant Development and Mitigates Normal Abiotic and Biotic Responses

PubMed Central

Goyal, Ravinder K.; Hancock, Robert E. W.; Mattoo, Autar K.; Misra, Santosh

2013-01-01

Antimicrobial cationic peptides (AMPs) are ubiquitous small proteins used by living cells to defend against a wide spectrum of pathogens. Their amphipathic property helps their interaction with negatively charged cellular membrane of the pathogen causing cell lysis and death. AMPs also modulate signaling pathway(s) and cellular processes in animal models; however, little is known of cellular processes other than the pathogen-lysis phenomenon modulated by AMPs in plants. An engineered heterologous AMP, msrA3, expressed in potato was previously shown to cause resistance of the transgenic plants against selected fungal and bacterial pathogens. These lines together with the wild type were studied for growth habits, and for inducible defense responses during challenge with biotic (necrotroph Fusarium solani) and abiotic stressors (dark-induced senescence, wounding and temperature stress). msrA3-expression not only conferred protection against F. solani but also delayed development of floral buds and prolonged vegetative phase. Analysis of select gene transcript profiles showed that the transgenic potato plants were suppressed in the hypersensitive (HR) and reactive oxygen species (ROS) responses to both biotic and abiotic stressors. Also, the transgenic leaves accumulated lesser amounts of the defense hormone jasmonic acid upon wounding with only a slight change in salicylic acid as compared to the wild type. Thus, normal host defense responses to the pathogen and abiotic stressors were mitigated by msrA3 expression suggesting MSRA3 regulates a common step(s) of these response pathways. The stemming of the pathogen growth and mitigating stress response pathways likely contributes to resource reallocation for higher tuber yield. PMID:24147012

Pathogen Phytosensing: Plants to Report Plant Pathogens.

PubMed

Mazarei, Mitra; Teplova, Irina; Hajimorad, M Reza; Stewart, C Neal

2008-04-14

Real-time systems that provide evidence of pathogen contamination in crops can be an important new line of early defense in agricultural centers. Plants possess defense mechanisms to protect against pathogen attack. Inducible plant defense is controlled by signal transduction pathways, inducible promoters and cis-regulatory elements corresponding to key genes involved in defense, and pathogen-specific responses. Identified inducible promoters and cis-acting elements could be utilized in plant sentinels, or 'phytosensors', by fusing these to reporter genes to produce plants with altered phenotypes in response to the presence of pathogens. Here, we have employed cis-acting elements from promoter regions of pathogen inducible genes as well as those responsive to the plant defense signal molecules salicylic acid, jasmonic acid, and ethylene. Synthetic promoters were constructed by combining various regulatory elements supplemented with the enhancer elements from the Cauliflower mosaic virus (CaMV) 35S promoter to increase basal level of the GUS expression. The inducibility of each synthetic promoter was first assessed in transient expression assays using Arabidopsis thaliana protoplasts and then examined for efficacy in stably transgenic Arabidopsis and tobacco plants. Histochemical and fluorometric GUS expression analyses showed that both transgenic Arabidopsis and tobacco plants responded to elicitor and phytohormone treatments with increased GUS expression when compared to untreated plants. Pathogen-inducible phytosensor studies were initiated by analyzing the sensitivity of the synthetic promoters against virus infection. Transgenic tobacco plants infected with Alfalfa mosaic virus showed an increase in GUS expression when compared to mock-inoculated control plants, whereas Tobacco mosaic virus infection caused no changes in GUS expression. Further research, using these transgenic plants against a range of different pathogens with the regulation of detectable reporter gene could provide biological evidence to define the functional differences between pathogens, and provide new technology and applications for transgenic plants as phytosensors.

Pathogen Screening of Naturally Produced Yakima River Spring Chinook Smolts; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2004-2005 Annual Report.

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

Thomas, Joan B.

2005-05-01

In the spring of 2004 naturally produced smolts outmigrating from the Yakima River Basin were collected for the sixth year of pathogen screening. This component of the evaluation is to monitor whether introduction of hatchery produced smolts would impact the prevalence of specific pathogens in the naturally produced spring chinook smolts. Increases in prevalence of any of these pathogens could negatively impact the survival of these fish. Since 1999 the Cle Elum Hatchery has been releasing spring chinook salmon smolts into the upper Yakima River to increase natural production. In 1998 and 2000 through 2004 naturally produced smolts were collectedmore » for monitoring at the Chandler smolt collection facility on the lower Yakima River. Smolts were collected from mid to late outmigration, with a target of 200 fish each year. The pathogens monitored were infectious hematopoeitic necrosis virus, infectious pancreatic necrosis virus, viral hemorrhagic septicemia virus, Flavobacterium psychrophilum, Flavobacterium columnare, Aeromonas salmonicida, Yersinia ruckeri, Edwardsiella ictaluri, Renibacterium salmoninarum and Myxobolus cerebralis. Of these pathogens, only R. salmoninarum was detected in very low levels in the naturally produced smolts outmigrating in 2004. To date, only bacterial pathogens have been detected and prevalences have been low. There have been small variations each year and these changes are attributed to normal fluctuations in prevalence. All of the pathogens detected are widely distributed in Washington State.« less

Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.

PubMed

Davidson, Donald J; Webb, Sheila; Teague, Peter; Govan, John R W; Dorin, Julia R

2004-01-01

To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains. We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background. We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose. These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR. Copyright 2004 S. Karger AG, Basel

Sequential effects of severe drought and defoliation on tree growth and survival in a diverse temperate mesic forest

NASA Astrophysics Data System (ADS)

Matthes, J. H.; Pederson, N.; David, O.; Martin-Benito, D.

2017-12-01

Understanding the effects of climate change and biotic disturbance within diverse temperate mesic forests is complicated by the need to scale between impacts within individuals and across species in the community. It is not clear how these impacts within individuals and across a community influences the stand- and regional-scale response. Furthermore, co-occurring or sequential disturbances can make it challenging to interpret forest responses from observational data. In the northeastern United States, the 1960s drought was perhaps the most severe period of climatic stress within the past 300 years and negatively impacted the growth of individual trees across all species, but unevenly. Additionally, in 1981 the northeast experienced an outbreak of the defoliator Lymantria dispar, which preferentially consumes oak leaves, but in 1981 impacted a high proportion of other species as well. To investigate the effects of drought (across functional groups) and defoliation (within a functional group), we combined a long-term tree-ring dataset from an old-growth forest within the Palmaghatt Ravine in New York with a version of the Ecosystem Demography model that includes a scheme for representing forest insects and pathogens. We explored the sequential impacts of severe drought and defoliation on tree growth, community composition, and ecosystem-atmosphere interactions (carbon, water, and heat flux). W­e also conducted a set of modeling experiments with climate and defoliation disturbance scenarios to bound the potential long-term response of this forest to co-occurring and sequential drought-defoliator disturbances over the next fifty years.

Immune Reconstitution Inflammatory Syndrome (IRIS): What pathologists should know.

PubMed

Nelson, Ann Marie; Manabe, Yukari C; Lucas, Sebastian B

2017-07-01

Antiretroviral therapy has significantly improved the quality and length of life for those patients able to access effective and sustained treatment. The resulting restoration of the immune response is associated with a change in the clinical presentation of opportunistic infections, and the histologic reaction to pathogens. A complex combination of alterations in host response across the stages of HIV infection has been documented over the past 3 decades. The defects are seen in both acute and chronic phases of inflammation and involve innate and adaptive immunity. In advanced stages of HIV infection, the marked disruption of lymphoid tissue and loss of follicular dendritic cells limits the host's ability to process antigen and mount specific responses to pathogens. There are qualitative and quantitative defects in CD4 T cells due to HIV infection. The resulting indirect effects include loss of cytokine production, dysregulation of B-cell function, loss of cellular mediated immunity and "holes" in the immunologic repertoire that may not be restored with the use of antiretroviral therapy. Immune reconstitution allows the host to respond to and control infection, but a significant number of patients will have atypical inflammatory syndromes during the recovery period. We briefly discuss the impact of HIV infection on the immune system and give an overview of the spectrum of conditions attributed to the Immune Reconstitution Inflammatory syndrome (IRIS). Copyright © 2017 Elsevier Inc. All rights reserved.

Benzo[a]pyrene exposure under future ocean acidification scenarios weakens the immune responses of blood clam, Tegillarca granosa.

PubMed

Su, Wenhao; Zha, Shanjie; Wang, Yichen; Shi, Wei; Xiao, Guoqiang; Chai, Xueliang; Wu, Hongxi; Liu, Guangxu

2017-04-01

Persistent organic pollutants (POPs) are known to converge into the ocean and accumulate in the sediment, posing great threats to marine organisms such as the sessile bottom burrowing bivalves. However, the immune toxicity of POPs, such as B[a]P, under future ocean acidification scenarios remains poorly understood to date. Therefore, in the present study, the impacts of B[a]P exposure on the immune responses of a bivalve species, Tegillarca granosa, under present and future ocean acidification scenarios were investigated. Results obtained revealed an increased immune toxicity of B[a]P under future ocean acidification scenarios in terms of reduced THC, altered haemocyte composition, and hampered phagocytosis, which may attribute to the synergetic effects of B[a]P and ocean acidification. In addition, the gene expressions of pathogen pattern recognition receptors (TLR1, TLR2, TLR4, TLR6), pathway mediators (TRAF6, TAK1, TAB2, IKKα and Myd88), and effectors (NF-ĸB) of the important immune related pathways were significantly down-regulated upon exposure to B[a]P under future ocean acidification scenarios. Results of the present study suggested an increased immune toxicity of B[a]P under future ocean acidification scenarios, which will significantly hamper the immune responses of T. granosa and subsequently render individuals more susceptible to pathogens challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses

DOE PAGES

Nafisi, Majse; Stranne, Maria; Fimognari, Lorenzo; ...

2015-07-22

Here we report that the epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. The cuticle layer appeared diffused and was significantly thicker and underneath cell wall layer was interspersed with electron-dense deposits. A large number of trichomes were collapsed andmore » surface permeability of the leaves was enhanced in rwa2 as compared to the wild type. A massive reprogramming of the transcriptome was observed in rwa2 as compared to the wild type, including a coordinated up-regulation of genes involved in responses to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis.« less

Disifin (sodium tosylchloramide) and Toll-like receptors (TLRs): evolving importance in health and diseases.

PubMed

Ofodile, Okom Nkili F C

2007-12-01

Disifin has emerged as a unique and very effective agent used in disinfection of wounds, disinfection of surfaces, materials and water, and other substances contaminated with almost every type of pathogenic microorganism ranging from viruses, bacteria, fungi and yeast, and, very possibly, protozoan parasites, as well. The major active component of Disifin is tosylchloramide sodium (chloramine T). However, the mechanism by which Disifin suppresses the activities of pathogenic microbial agents remains enigmatic. The molecular mechanisms, and the receptors and the signal transducing pathways responsible for the biological effects of Disifin are largely unknown. Despite considerable advances, enormous investigative efforts and large resources invested in the research on infectious diseases, microbial infection still remains a public health problem in many parts of the world. The exact nature of the pathogenic agents responsible for many infectious diseases, and the nature of the receptors mediating the associated inflammatory events are incompletely understood. Recent advances in understanding the molecular basis for mammalian host immune responses to microbial invasion suggest that the first line of defense against microbes is the recognition of pathogen-associated molecular patterns (PAMPs) by a family of transmembrane pattern-recognizing and signal transducing receptor proteins called Toll-like receptors (TLRs). The TLR family plays an instructive role in innate immune responses against microbial pathogens, as well as the subsequent induction of adaptive immune responses. TLRs mediate recognition and inflammatory responses to a wide range of microbial products and are crucial for effective host defense by eradication of the invading pathogens. Now, recent updates demonstrated the ability of Disifin-derived products, Disifin-Animal and Disifin-Pressant to effectively suppress the progression and activities of Chikungunya fever and that of avian influenza A virus [A/cardialis/Germany/72, H7N1: the agent of a highly pathogenic avian influenza (HPAI)] infection, respectively. Overall, the above findings led me to suggest that Disifin and TLRs may mechanistically overlap in the processes of executing their functions against pathogenic microbial organisms. Thus, elucidating and better understanding of the molecular underpinnings responsible for the biochemical effects of Disifin-products, and the nature and mode of the interaction(s) of Disifin with TLRs in the process of exerting their biological effects may open a novel dimension in the research of infectious diseases, which may provide novel therapeutic targets for the prevention and treatment of a wide range of infectious diseases.

Fluid fragmentation shapes rain-induced foliar disease transmission

PubMed Central

Gilet, T.; Bourouiba, L.

2015-01-01

Plant diseases represent a growing threat to the global food supply. The factors contributing to pathogen transmission from plant to plant remain poorly understood. Statistical correlations between rainfalls and plant disease outbreaks were reported; however, the detailed mechanisms linking the two were relegated to a black box. In this combined experimental and theoretical study, we focus on the impact dynamics of raindrops on infected leaves, one drop at a time. We find that the deposition range of most of the pathogen-bearing droplets is constrained by a hydrodynamical condition and we quantify the effect of leaf size and compliance on such constraint. Moreover, we identify and characterize two dominant fluid fragmentation scenarios as responsible for the dispersal of most pathogen-bearing droplets emitted from infected leaves: (i) the crescent-moon ejection is driven by the direct interaction between the impacting raindrop and the contaminated sessile drop and (ii) the inertial detachment is driven by the motion imparted to the leaf by the raindrop, leading to catapult-like droplet ejections. We find that at first, decreasing leaf size or increasing compliance reduces the range of pathogen-bearing droplets and the subsequent epidemic onset efficiency. However, this conclusion only applies for the crescent moon ejection. Above a certain compliance threshold a more effective mechanism of contaminated fluid ejection, the inertial detachment, emerges. This compliance threshold is determined by the ratio between the leaf velocity and the characteristic velocity of fluid fragmentation. The inertial detachment mechanism enhances the range of deposition of the larger contaminated droplets and suggests a change in epidemic onset pattern and a more efficient potential of infection of neighbouring plants. Dimensionless parameters and scaling laws are provided to rationalize our observations. Our results link for the first time the mechanical properties of foliage with the onset dynamics of foliar epidemics through the lens of fluid fragmentation. We discuss how the reported findings can inform the design of mitigation strategies acting at the early stage of a foliar disease outbreak. PMID:25652459

Prophenoloxidase system and its role in shrimp immune responses against major pathogens.

PubMed

Amparyup, Piti; Charoensapsri, Walaiporn; Tassanakajon, Anchalee

2013-04-01

The global shrimp industry still faces various serious disease-related problems that are mainly caused by pathogenic bacteria and viruses. Understanding the host defense mechanisms is likely to be beneficial in designing and implementing effective strategies to solve the current and future pathogen-related problems. Melanization, which is performed by phenoloxidase (PO) and controlled by the prophenoloxidase (proPO) activation cascade, plays an important role in the invertebrate immune system in allowing a rapid response to pathogen infection. The activation of the proPO system, by the specific recognition of microorganisms by pattern-recognition proteins (PRPs), triggers a serine proteinase cascade, eventually leading to the cleavage of the inactive proPO to the active PO that functions to produce the melanin and toxic reactive intermediates against invading pathogens. This review highlights the recent discoveries of the critical roles of the proPO system in the shrimp immune responses against major pathogens, and emphasizes the functional characterizations of four major groups of genes and proteins in the proPO cascade in penaeid shrimp, that is the PRPs, serine proteinases, proPO and inhibitors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

PubMed Central

Hörger, Anja C.; Ilyas, Muhammad; Stephan, Wolfgang; Tellier, Aurélien; van der Hoorn, Renier A. L.; Rose, Laura E.

2012-01-01

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant–pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the “Guard-Hypothesis,” R proteins (the “guards”) can sense modification of target molecules in the host (the “guardees”) by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the “guardee-effector” interface for pathogen recognition, natural selection acts on the “guard-guardee” interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen. PMID:22829777

Effects of climate change on the persistence and dispersal of foodborne bacterial pathogens in the outdoor environment: A review.

PubMed

Hellberg, Rosalee S; Chu, Eric

2016-08-01

According to the Intergovernmental Panel on Climate Change (IPCC), warming of the climate system is unequivocal. Over the coming century, warming trends such as increased duration and frequency of heat waves and hot extremes are expected in some areas, as well as increased intensity of some storm systems. Climate-induced trends will impact the persistence and dispersal of foodborne pathogens in myriad ways, especially for environmentally ubiquitous and/or zoonotic microorganisms. Animal hosts of foodborne pathogens are also expected to be impacted by climate change through the introduction of increased physiological stress and, in some cases, altered geographic ranges and seasonality. This review article examines the effects of climatic factors, such as temperature, rainfall, drought and wind, on the environmental dispersal and persistence of bacterial foodborne pathogens, namely, Bacillus cereus, Brucella, Campylobacter, Clostridium, Escherichia coli, Listeria monocytogenes, Salmonella, Staphylococcus aureus, Vibrio and Yersinia enterocolitica. These relationships are then used to predict how future climatic changes will impact the activity of these microorganisms in the outdoor environment and associated food safety issues. The development of predictive models that quantify these complex relationships will also be discussed, as well as the potential impacts of climate change on transmission of foodborne disease from animal hosts.

Battling the Bite: Tradeoffs in Immunity to Insect-Borne Pathogens.

PubMed

Schneider, David Samuel

2016-06-21

Effective pathogens are successful, by definition, because they can defeat our immune response. Pingen et al. (2016) in this issue of Immunity demonstrate that some mosquito-transmitted viruses depend upon a strong host immune response triggered by the innate immune response to the bite to promote dissemination through the body. Copyright © 2016. Published by Elsevier Inc.

Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission.

PubMed

Ren, Yuwei; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Zhang, Shujun

2017-01-01

Preventing pathogen transmission to a new host is of major interest to the immunologist and could benefit from a detailed investigation of pathogen immune evasion strategies. The first line of defense against pathogen invasion is provided by macrophages. When they sense pathogens, macrophages initiate signals to inflammatory and pro-inflammatory cytokines through pattern recognition receptors (PRRs) subsequently mediating phagocytosis and inflammation. The macrophage immune machinery classically includes two subsets: the activated M1 and the activated M2 that respond accordingly in diverse immune challenges. The lipid and glycogen metabolic pathways work together with the lysosome to help the mature phagosome to degrade and eliminate intracellular pathogens in macrophages. The viral evasion strategies are even more complex due to the interplay between autophagy and apoptosis. However, pathogens evolve several strategies to camouflage themselves against immune responses in order to ensure their survival, replication and transmission. These strategies include the muting of PRRs initiated inflammatory responses, attenuation of M1 and/or induction of M2 macrophages, suppression of autophago-lysosomal formation, interference with lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis cross-talk to enhance viral replication. This review focuses on pathogen immune evasion methods and on the strategies used by the host against camouflaged pathogens.

Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens. [Corrected].

PubMed

Wu, Liang; Chen, Huan; Curtis, Chad; Fu, Zheng Qing

2014-01-01

Plant resistance (R) proteins perceive specific pathogen effectors from diverse plant pathogens to initiate defense responses, designated effector-triggered immunity (ETI). Plant R proteins are mostly nucleotide binding-leucine rich repeat (NB-LRR) proteins, which recognize pathogen effectors directly or indirectly through sophisticated mechanisms. Upon activation by effector proteins, R proteins elicit robust defense responses, including a rapid burst of reactive oxygen species (ROS), induced biosynthesis and accumulation of salicylic acid (SA), a rapid programmed cell death (PCD) called hypersensitive response (HR) at the infection sites, and increased expression of pathogenesis-related (PR) genes. Initiation of ETI is correlated with a complex network of defense signaling pathways, resulting in defensive cellular responses and large-scale transcriptional reprogramming events. In this review, we highlight important recent advances on the recognition of effectors, regulation and activation of plant R proteins, dynamic intracellular trafficking of R proteins, induction of cell death, and transcriptional reprogramming associated with ETI. Current knowledge gaps and future research directions are also discussed in this review.

Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

PubMed

Gershwin, Laurel J; Van Eenennaam, Alison L; Anderson, Mark L; McEligot, Heather A; Shao, Matt X; Toaff-Rosenstein, Rachel; Taylor, Jeremy F; Neibergs, Holly L; Womack, James

2015-01-01

Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex

PubMed Central

Gershwin, Laurel J.; Van Eenennaam, Alison L.; Anderson, Mark L.; McEligot, Heather A.; Toaff-Rosenstein, Rachel; Taylor, Jeremy F.; Neibergs, Holly L.; Womack, James

2015-01-01

Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described. PMID:26571015

Immunity to intestinal pathogens: lessons learned from Salmonella

PubMed Central

McSorley, Stephen J.

2014-01-01

Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. PMID:24942689

The N-end rule pathway regulates pathogen responses in plants

PubMed Central

de Marchi, Rémi; Sorel, Maud; Mooney, Brian; Fudal, Isabelle; Goslin, Kevin; Kwaśniewska, Kamila; Ryan, Patrick T.; Pfalz, Marina; Kroymann, Juergen; Pollmann, Stephan; Feechan, Angela; Wellmer, Frank; Rivas, Susana; Graciet, Emmanuelle

2016-01-01

To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1. PMID:27173012

Elucidation of biocontrol mechanisms of Trichoderma harzianum against different plant fungal pathogens: Universal yet host specific response.

PubMed

Sharma, Vivek; Salwan, Richa; Sharma, Prem N; Kanwar, S S

2017-02-01

In the present study, different transcripts of Trichoderma harzianum ThHP-3 were evaluated for their response against four fungal pathogens Fusarium oxysporum, Colletotrichum capsici, Colletotrichum truncatum and Gloesercospora sorghi using RT-qPCR. The time course study of T. harzianum transcripts related to signal transduction, lytic enzymes, secondary metabolites and various transporters revealed variation in expression against four fungal pathogens. In a broader term, the transcripts were upregulated at various time intervals but the optimum expression of cyp3, abc, nrp, tga1, pmk, ech42 and glh20 varied with respect to host fungi. Additionally, the expression of transcripts related to transporters/cytochromes was also observed against Fusarium oxysporum after 96h whereas transcripts related to secondary metabolites and lytic enzymes showed significant difference in expression against Colletotrichum spp. from 72 to 96h. This is first study on transcriptomic response of T. harzianum against pathogenic fungi which shows their host specific response. Copyright © 2016 Elsevier B.V. All rights reserved.

Challenges in predicting climate and environmental effects on vector-borne disease episystems in a changing world.

PubMed

Tabachnick, W J

2010-03-15

Vector-borne pathogens cause enormous suffering to humans and animals. Many are expanding their range into new areas. Dengue, West Nile and Chikungunya have recently caused substantial human epidemics. Arthropod-borne animal diseases like Bluetongue, Rift Valley fever and African horse sickness pose substantial threats to livestock economies around the world. Climate change can impact the vector-borne disease epidemiology. Changes in climate will influence arthropod vectors, their life cycles and life histories, resulting in changes in both vector and pathogen distribution and changes in the ability of arthropods to transmit pathogens. Climate can affect the way pathogens interact with both the arthropod vector and the human or animal host. Predicting and mitigating the effects of future changes in the environment like climate change on the complex arthropod-pathogen-host epidemiological cycle requires understanding of a variety of complex mechanisms from the molecular to the population level. Although there has been substantial progress on many fronts the challenges to effectively understand and mitigate the impact of potential changes in the environment on vector-borne pathogens are formidable and at an early stage of development. The challenges will be explored using several arthropod-borne pathogen systems as illustration, and potential avenues to meet the challenges will be presented.

Pathogen Screening of Naturally Produced Yakima River Spring Chinook Smolts; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2001 Annual Report.

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

Pearsons, Todd N.; Thomas, Joan B.

2003-01-01

The change in pathogens prevalence to wild fish is probably the least studied ecological interaction associated with hatchery operations. In 1999, the Cle Elum Hatchery began releasing spring chinook smolts into the upper Yakima River to increase natural production. Part of the evaluation of this program is to evaluate whether introduction of hatchery produced smolts would impact the prevalence of specific pathogens in the naturally produced spring chinook smolts. Increases in prevalence of any of these pathogens could negatively impact the survival of these fish. Approximately 200 smolts were collected at the Chandler smolt collection facility on the lower Yakimamore » River during 1998, 2000 and 2001 and monitored for specific pathogens. The pathogens monitored were infectious hematopoeitic necrosis virus, infectious pancreatic necrosis virus, viral hemorrhagic septicemia, Flavobacterium psychrophilum, Flavobacterium columnare, Aeromonas salmonicida, Yersinia ruckeri, Edwardsiella ictaluri, Renibacterium salmoninarum and Myxobolus cerebralis. In addition, the fish were tested for Ceratomyxa shasta spores in 2001. Not all testing has been completed for every year, but to date, there have only been minimal changes in levels of the bacterial pathogens in the naturally produced smolts. At this point, due to the limited testing so far, these changes are attributed to normal fluctuation of prevalence.« less

Impacts of Climate Change on Indirect Human Exposure to Pathogens and Chemicals from Agriculture

PubMed Central

Boxall, Alistair B.A.; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D.; Haygarth, Philip M.; Hutchinson, Thomas; Kovats, R. Sari; Leonardi, Giovanni; Levy, Leonard S.; Nichols, Gordon; Parsons, Simon A.; Potts, Laura; Stone, David; Topp, Edward; Turley, David B.; Walsh, Kerry; Wellington, Elizabeth M.H.; Williams, Richard J.

2009-01-01

Objective Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes. PMID:19440487

A bacterial siren song: intimate interactions between neutrophils and pathogenic Neisseria

PubMed Central

Criss, Alison K.; Seifert, H. Steven

2012-01-01

Preface Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that are exquisitely adapted for growth at human mucosal surfaces and for efficient transmission between hosts. One factor that is essential to neisserial pathogenesis is the interaction between the bacteria and neutrophils, which are recruited in high numbers during infection. Although this vigorous host response could simply reflect effective immune recognition of the bacteria, there is mounting evidence that in fact these obligate human pathogens manipulate the innate immune response to promote infectious processes. This Review summarizes the mechanisms used by pathogenic neisseriae to resist and modulate the antimicrobial activities of neutrophils. It also details some of the major outstanding questions about the Neisseria–neutrophil relationship and proposes potential benefits of this relationship for the pathogen. PMID:22290508

A Role for a Menthone Reductase in Resistance against Microbial Pathogens in Plants1[C][W][OA

PubMed Central

Choi, Hyong Woo; Lee, Byung Gil; Kim, Nak Hyun; Park, Yong; Lim, Chae Woo; Song, Hyun Kyu; Hwang, Byung Kook

2008-01-01

Plants elaborate a vast array of enzymes that synthesize defensive secondary metabolites in response to pathogen attack. Here, we isolated the pathogen-responsive CaMNR1 [menthone: (+)-(3S)-neomenthol reductase] gene, a member of the short-chain dehydrogenase/reductase (SDR) superfamily, from pepper (Capsicum annuum) plants. Gas chromatography-mass spectrometry analysis revealed that purified CaMNR1 and its ortholog AtSDR1 from Arabidopsis (Arabidopsis thaliana) catalyze a menthone reduction with reduced nicotinamide adenine dinucleotide phosphate as a cofactor to produce neomenthol with antimicrobial activity. CaMNR1 and AtSDR1 also possess a significant catalytic activity for neomenthol oxidation. We examined the cellular function of the CaMNR1 gene by virus-induced gene silencing and ectopic overexpression in pepper and Arabidopsis plants, respectively. CaMNR1-silenced pepper plants were significantly more susceptible to Xanthomonas campestris pv vesicatoria and Colletotrichum coccodes infection and expressed lower levels of salicylic acid-responsive CaBPR1 and CaPR10 and jasmonic acid-responsive CaDEF1. CaMNR1-overexpressing Arabidopsis plants exhibited enhanced resistance to the hemibiotrophic pathogen Pseudomonas syringae pv tomato DC3000 and the biotrophic pathogen Hyaloperonospora parasitica isolate Noco2, accompanied by the induction of AtPR1 and AtPDF1.2. In contrast, mutation in the CaMNR1 ortholog AtSDR1 significantly enhanced susceptibility to both pathogens. Together, these results indicate that the novel menthone reductase gene CaMNR1 and its ortholog AtSDR1 positively regulate plant defenses against a broad spectrum of pathogens. PMID:18599651

Effects of immunostimulation on social behavior, chemical communication and genome-wide gene expression in honey bee workers (Apis mellifera)

PubMed Central

2012-01-01

Background Social insects, such as honey bees, use molecular, physiological and behavioral responses to combat pathogens and parasites. The honey bee genome contains all of the canonical insect immune response pathways, and several studies have demonstrated that pathogens can activate expression of immune effectors. Honey bees also use behavioral responses, termed social immunity, to collectively defend their hives from pathogens and parasites. These responses include hygienic behavior (where workers remove diseased brood) and allo-grooming (where workers remove ectoparasites from nestmates). We have previously demonstrated that immunostimulation causes changes in the cuticular hydrocarbon profiles of workers, which results in altered worker-worker social interactions. Thus, cuticular hydrocarbons may enable workers to identify sick nestmates, and adjust their behavior in response. Here, we test the specificity of behavioral, chemical and genomic responses to immunostimulation by challenging workers with a panel of different immune stimulants (saline, Sephadex beads and Gram-negative bacteria E. coli). Results While only bacteria-injected bees elicited altered behavioral responses from healthy nestmates compared to controls, all treatments resulted in significant changes in cuticular hydrocarbon profiles. Immunostimulation caused significant changes in expression of hundreds of genes, the majority of which have not been identified as members of the canonical immune response pathways. Furthermore, several new candidate genes that may play a role in cuticular hydrocarbon biosynthesis were identified. Effects of immune challenge expression of several genes involved in immune response, cuticular hydrocarbon biosynthesis, and the Notch signaling pathway were confirmed using quantitative real-time PCR. Finally, we identified common genes regulated by pathogen challenge in honey bees and other insects. Conclusions These results demonstrate that honey bee genomic responses to immunostimulation are substantially broader than the previously identified canonical immune response pathways, and may mediate the behavioral changes associated with social immunity by orchestrating changes in chemical signaling. These studies lay the groundwork for future research into the genomic responses of honey bees to native honey bee parasites and pathogens. PMID:23072398

Effects of immunostimulation on social behavior, chemical communication and genome-wide gene expression in honey bee workers (Apis mellifera).

PubMed

Richard, Freddie-Jeanne; Holt, Holly L; Grozinger, Christina M

2012-10-16

Social insects, such as honey bees, use molecular, physiological and behavioral responses to combat pathogens and parasites. The honey bee genome contains all of the canonical insect immune response pathways, and several studies have demonstrated that pathogens can activate expression of immune effectors. Honey bees also use behavioral responses, termed social immunity, to collectively defend their hives from pathogens and parasites. These responses include hygienic behavior (where workers remove diseased brood) and allo-grooming (where workers remove ectoparasites from nestmates). We have previously demonstrated that immunostimulation causes changes in the cuticular hydrocarbon profiles of workers, which results in altered worker-worker social interactions. Thus, cuticular hydrocarbons may enable workers to identify sick nestmates, and adjust their behavior in response. Here, we test the specificity of behavioral, chemical and genomic responses to immunostimulation by challenging workers with a panel of different immune stimulants (saline, Sephadex beads and Gram-negative bacteria E. coli). While only bacteria-injected bees elicited altered behavioral responses from healthy nestmates compared to controls, all treatments resulted in significant changes in cuticular hydrocarbon profiles. Immunostimulation caused significant changes in expression of hundreds of genes, the majority of which have not been identified as members of the canonical immune response pathways. Furthermore, several new candidate genes that may play a role in cuticular hydrocarbon biosynthesis were identified. Effects of immune challenge expression of several genes involved in immune response, cuticular hydrocarbon biosynthesis, and the Notch signaling pathway were confirmed using quantitative real-time PCR. Finally, we identified common genes regulated by pathogen challenge in honey bees and other insects. These results demonstrate that honey bee genomic responses to immunostimulation are substantially broader than the previously identified canonical immune response pathways, and may mediate the behavioral changes associated with social immunity by orchestrating changes in chemical signaling. These studies lay the groundwork for future research into the genomic responses of honey bees to native honey bee parasites and pathogens.

Survey of Innate Immune Responses to Burkholderia pseudomallei in Human Blood Identifies a Central Role for Lipopolysaccharide

PubMed Central

Chantratita, Narisara; Tandhavanant, Sarunporn; Myers, Nicolle D.; Seal, Sudeshna; Arayawichanont, Arkhom; Kliangsa-ad, Aroonsri; Hittle, Lauren E.; Ernst, Robert K.; Emond, Mary J.; Wurfel, Mark M.; Day, Nicholas P. J.; Peacock, Sharon J.; West, T. Eoin

2013-01-01

B. pseudomallei is a gram-negative bacterium that causes the tropical infection melioidosis. In northeast Thailand, mortality from melioidosis approaches 40%. As exemplified by the lipopolysaccharide-Toll-like receptor 4 interaction, innate immune responses to invading bacteria are precipitated by activation of host pathogen recognition receptors by pathogen associated molecular patterns. Human melioidosis is characterized by up-regulation of pathogen recognition receptors and pro-inflammatory cytokine release. In contrast to many gram-negative pathogens, however, the lipopolysaccharide of B. pseudomallei is considered only weakly inflammatory. We conducted a study in 300 healthy Thai subjects to investigate the ex vivo human blood response to various bacterial pathogen associated molecular patterns, including lipopolysaccharide from several bacteria, and to two heat-killed B. pseudomallei isolates. We measured cytokine levels after stimulation of fresh whole blood with a panel of stimuli. We found that age, sex, and white blood cell count modulate the innate immune response to B. pseudomallei. We further observed that, in comparison to other stimuli, the innate immune response to B. pseudomallei is most highly correlated with the response to lipopolysaccharide. The magnitude of cytokine responses induced by B. pseudomallei lipopolysaccharide was significantly greater than those induced by lipopolysaccharide from Escherichia coli and comparable to many responses induced by lipopolysaccharide from Salmonella minnesota despite lower amounts of lipid A in the B. pseudomallei lipopolysaccharide preparation. In human monocytes stimulated with B. pseudomallei, addition of polymyxin B or a TLR4/MD-2 neutralizing antibody inhibited the majority of TNF-α production. Challenging existing views, our data indicate that the innate immune response to B. pseudomallei in human blood is largely driven by lipopolysaccharide, and that the response to B. pseudomallei lipopolysaccharide in blood is greater than the response to other lipopolysaccharide expressing isolates. Our findings suggest that B. pseudomallei lipopolysaccharide may play a central role in stimulating the host response in melioidosis. PMID:24303060

Development and experimental validation of a 20K Atlantic cod (Gadus morhua) oligonucleotide microarray based on a collection of over 150,000 ESTs.

PubMed

Booman, Marije; Borza, Tudor; Feng, Charles Y; Hori, Tiago S; Higgins, Brent; Culf, Adrian; Léger, Daniel; Chute, Ian C; Belkaid, Anissa; Rise, Marlies; Gamperl, A Kurt; Hubert, Sophie; Kimball, Jennifer; Ouellette, Rodney J; Johnson, Stewart C; Bowman, Sharen; Rise, Matthew L

2011-08-01

The collapse of Atlantic cod (Gadus morhua) wild populations strongly impacted the Atlantic cod fishery and led to the development of cod aquaculture. In order to improve aquaculture and broodstock quality, we need to gain knowledge of genes and pathways involved in Atlantic cod responses to pathogens and other stressors. The Atlantic Cod Genomics and Broodstock Development Project has generated over 150,000 expressed sequence tags from 42 cDNA libraries representing various tissues, developmental stages, and stimuli. We used this resource to develop an Atlantic cod oligonucleotide microarray containing 20,000 unique probes. Selection of sequences from the full range of cDNA libraries enables application of the microarray for a broad spectrum of Atlantic cod functional genomics studies. We included sequences that were highly abundant in suppression subtractive hybridization (SSH) libraries, which were enriched for transcripts responsive to pathogens or other stressors. These sequences represent genes that potentially play an important role in stress and/or immune responses, making the microarray particularly useful for studies of Atlantic cod gene expression responses to immune stimuli and other stressors. To demonstrate its value, we used the microarray to analyze the Atlantic cod spleen response to stimulation with formalin-killed, atypical Aeromonas salmonicida, resulting in a gene expression profile that indicates a strong innate immune response. These results were further validated by quantitative PCR analysis and comparison to results from previous analysis of an SSH library. This study shows that the Atlantic cod 20K oligonucleotide microarray is a valuable new tool for Atlantic cod functional genomics research.

Presence of Pathogens and Indicator Microbes at a Non-Point Source Subtropical Recreational Marine Beach ▿ †

PubMed Central

Abdelzaher, Amir M.; Wright, Mary E.; Ortega, Cristina; Solo-Gabriele, Helena M.; Miller, Gary; Elmir, Samir; Newman, Xihui; Shih, Peter; Bonilla, J. Alfredo; Bonilla, Tonya D.; Palmer, Carol J.; Scott, Troy; Lukasik, Jerzy; Harwood, Valerie J.; McQuaig, Shannon; Sinigalliano, Chris; Gidley, Maribeth; Plano, Lisa R. W.; Zhu, Xiaofang; Wang, John D.; Fleming, Lora E.

2010-01-01

Swimming in ocean water, including ocean water at beaches not impacted by known point sources of pollution, is an increasing health concern. This study was an initial evaluation of the presence of indicator microbes and pathogens and the association among the indicator microbes, pathogens, and environmental conditions at a subtropical, recreational marine beach in south Florida impacted by non-point sources of pollution. Twelve water and eight sand samples were collected during four sampling events at high or low tide under elevated or reduced solar insolation conditions. The analyses performed included analyses of fecal indicator bacteria (FIB) (fecal coliforms, Escherichia coli, enterococci, and Clostridium perfringens), human-associated microbial source tracking (MST) markers (human polyomaviruses [HPyVs] and Enterococcus faecium esp gene), and pathogens (Vibrio vulnificus, Staphylococcus aureus, enterovirus, norovirus, hepatitis A virus, Cryptosporidium spp., and Giardia spp.). The enterococcus concentrations in water and sand determined by quantitative PCR were greater than the concentrations determined by membrane filtration measurement. The FIB concentrations in water were below the recreational water quality standards for three of the four sampling events, when pathogens and MST markers were also generally undetectable. The FIB levels exceeded regulatory guidelines during one event, and this was accompanied by detection of HPyVs and pathogens, including detection of the autochthonous bacterium V. vulnificus in sand and water, detection of the allochthonous protozoans Giardia spp. in water, and detection of Cryptosporidium spp. in sand samples. The elevated microbial levels were detected at high tide and under low-solar-insolation conditions. Additional sampling should be conducted to further explore the relationships between tidal and solar insolation conditions and between indicator microbes and pathogens in subtropical recreational marine waters impacted by non-point source pollution. PMID:19966020

A nitrogen response pathway regulates virulence in plant pathogenic fungi: role of TOR and the bZIP protein MeaB.

PubMed

López-Berges, Manuel S; Rispail, Nicolas; Prados-Rosales, Rafael C; Di Pietro, Antonio

2010-12-01

Virulence in plant pathogenic fungi is controlled through a variety of cellular pathways in response to the host environment. Nitrogen limitation has been proposed to act as a key signal to trigger the in planta expression of virulence genes. Moreover, a conserved Pathogenicity mitogen activated protein kinase (MAPK) cascade is strictly required for plant infection in a wide range of pathogens. We investigated the relationship between nitrogen signaling and the Pathogenicity MAPK cascade in controlling infectious growth of the vascular wilt fungus Fusarium oxysporum. Several MAPK-activated virulence functions such as invasive growth, vegetative hyphal fusion and host adhesion were strongly repressed in the presence of the preferred nitrogen source ammonium. Repression of these functions by ammonium was abolished by L-Methionine sulfoximine (MSX) or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR (Target Of Rapamycin), respectively, and was dependent on the bZIP protein MeaB. Supplying tomato plants with ammonium rather than nitrate resulted in a significant delay of vascular wilt symptoms caused by the F. oxysporum wild type strain, but not by the ΔmeaB mutant. Ammonium also repressed invasive growth in two other pathogens, the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. Our results suggest the presence of a conserved nitrogen-responsive pathway that operates via TOR and MeaB to control infectious growth in plant pathogenic fungi.

Extracellular Alkalinization as a Defense Response in Potato Cells.

PubMed

Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu

2017-01-01

A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

Differential Expression of Inflammatory Cytokines and Stress Genes in Male and Female Mice in Response to a Lipopolysaccharide Challenge

PubMed Central

Everhardt Queen, Ashleigh; Moerdyk-Schauwecker, Megan; McKee, Leslie M.; Leamy, Larry J.

2016-01-01

Background Sex plays a key role in an individual’s immune response against pathogenic challenges such that females fare better when infected with certain pathogens. It is thought that sex hormones impact gene expression in immune cells and lead to sexually dimorphic responses to pathogens. We predicted that, in the presence of E. coli gram-negative lipopolysaccharide (LPS), there would be a sexually dimorphic response in proinflammatory cytokine production and acute phase stress gene expression and that these responses might vary among different mouse strains and times in a pattern opposite to that of body temperature associated with LPS-induced shock. Materials and Methods Interleukin-6 (IL-6), macrophage inflammatory protein-Iβ (MIP-1β), tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) as well as beta-fibrinogen (Fgb) and metallothionein-1 (Mt-1) mRNA expression were measured at four time points (0, 2, 4 and 7 hours) after injection of E. coli LPS in mice from three inbred strains. Results Statistical analysis using analyses of variance (ANOVAs) showed that the levels of the all six traits changed over time, generally peaking at 2 hours after LPS injection. Mt-1, Fgb, and IL-6 showed differences among strains, although these were time-specific. Sexual dimorphism was seen for Fgb and IL6, and was most pronounced at the latest time period (7 hours) where male levels exceeded those for females. Trends for all six cytokine/gene expression traits were negatively correlated with those for body temperatures. Discussion The higher levels of expression of Fgb and IL6 in males compared with females are consistent with the greater vulnerability of males to infection and subsequent inflammation. Temperature appears to be a useful proxy for mortality in endotoxic shock, but sexual dimorphism in cytokine and stress gene expression levels may persist after an LPS challenge even if temperatures in the two sexes are similar and have begun to stabilize. PMID:27120355

Absence of Nucleotide-Oligomerization-Domain-2 Is Associated with Less Distinct Disease in Campylobacter jejuni Infected Secondary Abiotic IL-10 Deficient Mice.

PubMed

Heimesaat, Markus M; Grundmann, Ursula; Alutis, Marie E; Fischer, André; Bereswill, Stefan

2017-01-01

Human Campylobacter jejuni -infections are progressively increasing worldwide. Despite their high prevalence and socioeconomic impact the underlying mechanisms of pathogen-host-interactions are only incompletely understood. Given that the innate immune receptor nucleotide-oligomerization-domain-2 (Nod2) is involved in clearance of enteropathogens, we here evaluated its role in murine campylobacteriosis. To address this, we applied Nod2-deficient IL-10 -/- (Nod2 -/- IL-10 -/- ) mice and IL-10 -/- counterparts both with a depleted intestinal microbiota to warrant pathogen-induced enterocolitis. At day 7 following peroral C. jejuni strain 81-176 infection, Nod2 mRNA was down-regulated in the colon of secondary abiotic IL-10 -/- and wildtype mice. Nod2-deficiency did neither affect gastrointestinal colonization nor extra-intestinal and systemic translocation properties of C. jejuni . Colonic mucin-2 mRNA was, however, down-regulated upon C. jejuni -infection of both Nod2 -/- IL-10 -/- and IL-10 -/- mice, whereas expression levels were lower in infected, but also naive Nod2 -/- IL-10 -/- mice as compared to respective IL-10 -/- controls. Remarkably, C. jejuni -infected Nod2 -/- IL-10 -/- mice were less compromised than IL-10 -/- counterparts and displayed less distinct apoptotic, but higher regenerative cell responses in colonic epithelia. Conversely, innate as well as adaptive immune cells such as macrophages and monocytes as well as T lymphocytes and regulatory T-cells, respectively, were even more abundant in large intestines of Nod2 -/- IL-10 -/- as compared to IL-10 -/- mice at day 7 post-infection. Furthermore, IFN-γ concentrations were higher in ex vivo biopsies derived from intestinal compartments including colon and mesenteric lymph nodes as well as in systemic tissue sites such as the spleen of C. jejuni infected Nod2 -/- IL-10 -/- as compared to IL10 -/- counterparts. Whereas, at day 7 postinfection anti-inflammatory IL-22 mRNA levels were up-regulated, IL-18 mRNA was down-regulated in large intestines of Nod2 -/- IL-10 -/- vs. IL-10 -/- mice. In summary, C. jejuni -infection induced less clinical signs and apoptosis, but more distinct colonic pro- and (of note) anti-inflammatory immune as well as regenerative cell responses in Nod2 deficient IL-10 -/- as compared to IL-10 -/- control mice. We conclude that, even though colonic Nod2 mRNA was down-regulated upon pathogenic challenge, Nod2-signaling is essentially involved in the well-balanced innate and adaptive immune responses upon C. jejuni -infection of secondary abiotic IL-10 -/- mice, but does neither impact pathogenic colonization nor translocation.

Tree immunity: growing old without antibodies.

PubMed

Tobias, Peri A; Guest, David I

2014-06-01

Perennial plants need to cope with changing environments and pathogens over their lifespan. Infections are compartmentalised by localised physiological responses, and multiple apical meristems enable repair and regrowth, but genes are another crucial component in the perception and response to pathogens. In this opinion article we suggest that the mechanism for dynamic pathogen-specific recognition in long-lived plants could be explained by extending our current understanding of plant defence genes. We propose that, in addition to physiological responses, tree defence uses a three-pronged genomic approach involving: (i) gene numbers, (ii) genomic architecture, and (iii) mutation loads accumulated over long lifespans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity

PubMed Central

Argueso, Cristiana T.; Ferreira, Fernando J.; Epple, Petra; To, Jennifer P. C.; Hutchison, Claire E.; Schaller, G. Eric; Dangl, Jeffery L.; Kieber, Joseph J.

2012-01-01

Recent studies have revealed an important role for hormones in plant immunity. We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions. Cytokinins are plant hormones that regulate development and responses to the environment. Cytokinin signaling involves a phosphorelay circuitry similar to two-component systems used by bacteria and fungi to perceive and react to various environmental stimuli. In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of basal and pathogen-induced SA–dependent gene expression. Our results support a model in which cytokinin up-regulates plant immunity via an elevation of SA–dependent defense responses and in which SA in turn feedback-inhibits cytokinin signaling. The crosstalk between cytokinin and SA signaling networks may help plants fine-tune defense responses against pathogens. PMID:22291601

NS Segment of a 1918 Influenza A Virus-Descendent Enhances Replication of H1N1pdm09 and Virus-Induced Cellular Immune Response in Mammalian and Avian Systems

PubMed Central

Petersen, Henning; Mostafa, Ahmed; Tantawy, Mohamed A.; Iqbal, Azeem A.; Hoffmann, Donata; Tallam, Aravind; Selvakumar, Balachandar; Pessler, Frank; Beer, Martin; Rautenschlein, Silke; Pleschka, Stephan

2018-01-01

The 2009 pandemic influenza A virus (IAV) H1N1 strain (H1N1pdm09) has widely spread and is circulating in humans and swine together with other human and avian IAVs. This fact raises the concern that reassortment between H1N1pdm09 and co-circulating viruses might lead to an increase of H1N1pdm09 pathogenicity in different susceptible host species. Herein, we explored the potential of different NS segments to enhance the replication dynamics, pathogenicity and host range of H1N1pdm09 strain A/Giessen/06/09 (Gi-wt). The NS segments were derived from (i) human H1N1- and H3N2 IAVs, (ii) highly pathogenic- (H5- or H7-subtypes) or (iii) low pathogenic avian influenza viruses (H7- or H9-subtypes). A significant increase of growth kinetics in A549 (human lung epithelia) and NPTr (porcine tracheal epithelia) cells was only noticed in vitro for the reassortant Gi-NS-PR8 carrying the NS segment of the 1918-descendent A/Puerto Rico/8/34 (PR8-wt, H1N1), whereas all other reassortants showed either reduced or comparable replication efficiencies. Analysis using ex vivo tracheal organ cultures of turkeys (TOC-Tu), a species susceptible to IAV H1N1 infection, demonstrated increased replication of Gi-NS-PR8 compared to Gi-wt. Also, Gi-NS-PR8 induced a markedly higher expression of immunoregulatory and pro-inflammatory cytokines, chemokines and interferon-stimulated genes in A549 cells, THP-1-derived macrophages (dHTP) and TOC-Tu. In vivo, Gi-NS-PR8 induced an earlier onset of mortality than Gi-wt in mice, whereas, 6-week-old chickens were found to be resistant to both viruses. These data suggest that the specific characteristics of the PR8 NS segments can impact on replication, virus induced cellular immune responses and pathogenicity of the H1N1pdm09 in different avian and mammalian host species. PMID:29623073

Perception of low red:far-red ratio compromises both salicylic acid- and jasmonic acid-dependent pathogen defences in Arabidopsis.

PubMed

de Wit, Mieke; Spoel, Steven H; Sanchez-Perez, Gabino F; Gommers, Charlotte M M; Pieterse, Corné M J; Voesenek, Laurentius A C J; Pierik, Ronald

2013-07-01

In dense stands of plants, such as agricultural monocultures, plants are exposed simultaneously to competition for light and other stresses such as pathogen infection. Here, we show that both salicylic acid (SA)-dependent and jasmonic acid (JA)-dependent disease resistance is inhibited by a simultaneously reduced red:far-red light ratio (R:FR), the early warning signal for plant competition. Conversely, SA- and JA-dependent induced defences did not affect shade-avoidance responses to low R:FR. Reduced pathogen resistance by low R:FR was accompanied by a strong reduction in the regulation of JA- and SA-responsive genes. The severe inhibition of SA-responsive transcription in low R:FR appeared to be brought about by the repression of SA-inducible kinases. Phosphorylation of the SA-responsive transcription co-activator NPR1, which is required for full induction of SA-responsive transcription, was indeed reduced and may thus play a role in the suppression of SA-mediated defences by low R:FR-mediated phytochrome inactivation. Our results indicate that foraging for light through the shade-avoidance response is prioritised over plant immune responses when plants are simultaneously challenged with competition and pathogen attack. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Pathogen Screening of Naturally Produced Yakima River Spring Chinook Smolts; Yakima/Klickitat Fisheries Project Monitoring and Evaluation Report 6 of 7, 2003-2004 Annual Report.

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

Thomas, Joan B.

2004-05-01

In 1999 the Cle Elum Hatchery began releasing spring chinook salmon smolts into the upper Yakima River to increase natural production. Part of the evaluation of this program is to monitor whether introduction of hatchery produced smolts would impact the prevalence of specific pathogens in the naturally produced spring chinook smolts. Increases in prevalence of any of these pathogens could negatively impact the survival of these fish. In 1998 and 2000 through 2003 naturally produced smolts were collected for monitoring at the Chandler smolt collection facility on the lower Yakima River. Smolts were collected from mid to late outmigration, withmore » a target of 200 fish each year. The pathogens monitored were infectious hematopoeitic necrosis virus, infectious pancreatic necrosis virus, viral hemorrhagic septicemia virus, Flavobacterium psychrophilum, Flavobacterium columnare, Aeromonas salmonicida, Yersinia ruckeri, Edwardsiella ictaluri, Renibacterium salmoninarum and Myxobolus cerebralis. To date, only the bacterial pathogens have been detected and prevalences have been low. Prevalences have varied each year and these changes are attributed to normal fluctuation of prevalence. All of the pathogens detected are widely distributed in Washington State.« less

Pathogen Screening of Naturally Produced Yakima River Spring Chinook Smolts; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2002 Annual Report.

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

Thomas, Joan B.

2003-05-01

In 1999 the Cle Elem Hatchery began releasing spring chinook smolts into the upper Yakima River for restoration and supplementation. This project was designed to evaluate whether introduction of intensively reared hatchery produced smolts would impact the prevalence of specific pathogens in the naturally produced spring chinook smolts. Increases in prevalence of any of these pathogens could negatively impact the survival of these fish. Approximately 200 smolts were collected at the Chandler smolt collection facility on the lower Yakima River during 1998, 2000 and 2001 and 130 smolts were collected in 2002 for monitoring for specific pathogens. The pathogens monitoredmore » were infectious hematopoeitic necrosis virus, infectious pancreatic necrosis virus, viral hemorrhagic septicemia, Flavobacterium psychrophilum, Flavobacterium columnare, Aeromonas salmonicida, Yersinia ruckeri, Edwardsiella ictaluri, Renibacterium salmoninarum and Myxobolus cerebralis. In addition the fish were tested for Ceratomyxa shasta spores in 2000 and 2001 (a correction from the 2001 report). To date, the only changes have been in the levels the bacterial pathogens in the naturally produced smolts and they have been minimal. These changes are attributed to normal fluctuation of prevalence.« less

The impact of "ancient pathogen" studies on the practice of public health.

PubMed

Greenblatt, Charles; Spigelman, Mark; Vernon, Kim

2003-01-01

A new field of "ancient pathogens" is making an impact on our concepts of the evolution of infectious diseases, and it will eventually alter the practice of public health in their control. It has begun to answer important questions regarding past epidemics of influenza and tuberculosis by recovering the genetic sequences of the ancient causative agents. Vaccination strategics will have to study these microbial variants in order to develop tomorrow's vaccines. It may also be possible to examine the role of past and present reservoirs in the dynamics of emerging diseases. In unraveling the evolution of pathogens, insights into the mechanisms of drug and antibiotic resistance are possible. As "genome projects" of more and more pathogens are being completed. Targets for chemotherapy are being revealed which are totally different from the metabolic processes of the mammalian host. Signal molecules are being identified which alter the virulence of the microbe. Focussing on these mechanisms without attempting to kill the pathogen may in some cases drive it into a benign state. These and other aspects of the evolution of pathogens are discussed which may lead to innovative approaches to the control of infectious diseases.

Aquatic polymers can drive pathogen transmission in coastal ecosystems

PubMed Central

Shapiro, Karen; Krusor, Colin; Mazzillo, Fernanda F. M.; Conrad, Patricia A.; Largier, John L.; Mazet, Jonna A. K.; Silver, Mary W.

2014-01-01

Gelatinous polymers including extracellular polymeric substances (EPSs) are fundamental to biophysical processes in aquatic habitats, including mediating aggregation processes and functioning as the matrix of biofilms. Yet insight into the impact of these sticky molecules on the environmental transmission of pathogens in the ocean is limited. We used the zoonotic parasite Toxoplasma gondii as a model to evaluate polymer-mediated mechanisms that promote transmission of terrestrially derived pathogens to marine fauna and humans. We show that transparent exopolymer particles, a particulate form of EPS, enhance T. gondii association with marine aggregates, material consumed by organisms otherwise unable to access micrometre-sized particles. Adhesion to EPS biofilms on macroalgae also captures T. gondii from the water, enabling uptake of pathogens by invertebrates that feed on kelp surfaces. We demonstrate the acquisition, concentration and retention of T. gondii by kelp-grazing snails, which can transmit T. gondii to threatened California sea otters. Results highlight novel mechanisms whereby aquatic polymers facilitate incorporation of pathogens into food webs via association with particle aggregates and biofilms. Identifying the critical role of invisible polymers in transmission of pathogens in the ocean represents a fundamental advance in understanding and mitigating the health impacts of coastal habitat pollution with contaminated runoff. PMID:25297861

The chicken TH1 response: potential therapeutic applications of ChIFN-γ.

PubMed

Guo, Pengju; Thomas, Jesse D; Bruce, Matthew P; Hinton, Tracey M; Bean, Andrew G D; Lowenthal, John W

2013-11-01

The outcomes of viral infections are costly in terms of human and animal health and welfare worldwide. The observed increase in the virulence of some viruses and failure of many vaccines to stop these infections has lead to the apparent need to develop new anti-viral strategies. One approach to dealing with viral infection may be to employ the therapeutic administration of recombinant cytokines to act as 'immune boosters' to assist in augmenting the host response to virus. With this in mind, a greater understanding of the immune response, particularly cell mediated T-helper-1 (TH1) type responses, is imperative to the development of new anti-viral and vaccination strategies. Following the release of the chicken genome, a number of TH1-type cytokines have been identified, including chicken interleukin-12 (ChIL-12), ChIL-18 and interferon-γ ChIFN-γ), highlighting the nature of the TH1-type response in this non-mammalian vertebrate. To date a detailed analysis of the in vivo biological function of these cytokines has been somewhat hampered by access to large scale production techniques. This review describes the role of TH-1 cytokines in immune responses to viruses and explores their potential use in enhancing anti-viral treatment strategies in chickens. Furthermore, this review focuses on the example of ChIFN-γ treatment of Chicken Anemia Virus (CAV) infection. CAV causes amongst other things thymocyte depletion and thymus atrophy, as well as immunosuppression in chickens. However, due to vaccination, clinical disease appears less often, nevertheless, the subclinical form of the disease is often associated with secondary complicating infections due to an immunocompromised state. Since CAV-induced immunosuppression can cause a marked decrease in the immune response against other pathogens, understanding this aspect of the disease is critically important, as well as providing insights into developing new control approaches. With increasing emphasis on developing alternative control programs for poultry diseases, novel therapeutic strategies provide one approach. We show here that the in ovo administration of ChIFN-γ impacts the depletion of T-cell precursors during CAV infection. Therefore, it appears that ChIFN-γ may have the potential to be used as a novel therapeutic reagent to impact virus infection and alter immunosuppression caused by CAV and potentially other pathogens. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Invited review: Mastitis in dairy heifers: nature of the disease, potential impact, prevention, and control.

PubMed

De Vliegher, S; Fox, L K; Piepers, S; McDougall, S; Barkema, H W

2012-03-01

Heifer mastitis is a disease that potentially threatens production and udder health in the first and subsequent lactations. In general, coagulase-negative staphylococci (CNS) are the predominant cause of intramammary infection and subclinical mastitis in heifers around parturition, whereas Staphylococcus aureus and environmental pathogens cause a minority of the cases. Clinical heifer mastitis is typically caused by the major pathogens. The variation in proportions of causative pathogens between studies, herds, and countries is considerable. The magnitude of the effect of heifer mastitis on an individual animal is influenced by the form of mastitis (clinical versus subclinical), the virulence of the causative pathogen(s) (major versus minor pathogens), the time of onset of infection relative to calving, cure or persistence of the infection when milk production has started, and the host's immunity. Intramammary infection in early lactation caused by CNS does not generally have a negative effect on subsequent productivity. At the herd level, the impact will depend on the prevalence and incidence of the disease, the nature of the problem (clinical, subclinical, nonfunctional quarters), the causative pathogens involved (major versus minor pathogens), the ability of the animals to cope with the disease, and the response of the dairy manager to control the disease through management changes. Specific recommendations to prevent and control mastitis in late gestation in periparturient heifers are not part of the current National Mastitis Council mastitis and prevention program. Control and prevention is currently based on avoidance of inter-sucking among young stock, fly control, optimal nutrition, and implementation of hygiene control and comfort measures, especially around calving. More risk factors for subclinical and clinical heifer mastitis have been identified (e.g., season, location of herd, stage of pregnancy) although they do not lend themselves to the development of specific intervention strategies designed to prevent the disease. Pathogen-specific risk factors and associated control measures need to be identified due to the pathogen-related variation in epidemiology and effect on future performance. Prepartum intramammary treatment with antibiotics has been proposed as a simple and effective way of controlling heifer mastitis but positive long-lasting effects on somatic cell count and milk yield do not always occur, ruling out universal recommendation of this practice. Moreover, use of antibiotics in this manner is off-label and results in an increased risk of antibiotic residues in milk. Prepartum treatment can be implemented only as a short-term measure to assist in the control of a significant heifer mastitis problem under supervision of the herd veterinarian. When CNS are the major cause of intramammary infection in heifers, productivity is not affected, making prepartum treatment redundant and even unwanted. In conclusion, heifer mastitis can affect the profitability of dairy farming because of a potential long-term negative effect on udder health and milk production and an associated culling risk, specifically when major pathogens are involved. Prevention and control is not easy but is possible through changes in young stock and heifer management. However, the pathogenesis and epidemiology of the disease remain largely unknown and more pathogen-specific risk factors should be identified to optimize current prevention programs. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Consequences of non-intervention for infectious disease in African great apes.

PubMed

Ryan, Sadie J; Walsh, Peter D

2011-01-01

Infectious disease has recently joined poaching and habitat loss as a major threat to African apes. Both "naturally" occurring pathogens, such as Ebola and Simian Immunodeficiency Virus (SIV), and respiratory pathogens transmitted from humans, have been confirmed as important sources of mortality in wild gorillas and chimpanzees. While awareness of the threat has increased, interventions such as vaccination and treatment remain controversial. Here we explore both the risk of disease to African apes, and the status of potential responses. Through synthesis of published data, we summarize prior disease impact on African apes. We then use a simple demographic model to illustrate the resilience of a well-known gorilla population to disease, modeled on prior documented outbreaks. We found that the predicted recovery time for this specific gorilla population from a single outbreak ranged from 5 years for a low mortality (4%) respiratory outbreak, to 131 years for an Ebola outbreak that killed 96% of the population. This shows that mortality rates comparable to those recently reported for disease outbreaks in wild populations are not sustainable. This is particularly troubling given the rising pathogen risk created by increasing habituation of wild apes for tourism, and the growth of human populations surrounding protected areas. We assess potential future disease spillover risk in terms of vaccination rates amongst humans that may come into contact with wild apes, and the availability of vaccines against potentially threatening diseases. We discuss and evaluate non-interventionist responses such as limiting tourist access to apes, community health programs, and safety, logistic, and cost issues that constrain the potential of vaccination. © 2011 Ryan and Walsh.

Consequences of Non-Intervention for Infectious Disease in African Great Apes

PubMed Central

Ryan, Sadie J.; Walsh, Peter D.

2011-01-01

Infectious disease has recently joined poaching and habitat loss as a major threat to African apes. Both “naturally” occurring pathogens, such as Ebola and Simian Immunodeficiency Virus (SIV), and respiratory pathogens transmitted from humans, have been confirmed as important sources of mortality in wild gorillas and chimpanzees. While awareness of the threat has increased, interventions such as vaccination and treatment remain controversial. Here we explore both the risk of disease to African apes, and the status of potential responses. Through synthesis of published data, we summarize prior disease impact on African apes. We then use a simple demographic model to illustrate the resilience of a well-known gorilla population to disease, modeled on prior documented outbreaks. We found that the predicted recovery time for this specific gorilla population from a single outbreak ranged from 5 years for a low mortality (4%) respiratory outbreak, to 131 years for an Ebola outbreak that killed 96% of the population. This shows that mortality rates comparable to those recently reported for disease outbreaks in wild populations are not sustainable. This is particularly troubling given the rising pathogen risk created by increasing habituation of wild apes for tourism, and the growth of human populations surrounding protected areas. We assess potential future disease spillover risk in terms of vaccination rates amongst humans that may come into contact with wild apes, and the availability of vaccines against potentially threatening diseases. We discuss and evaluate non-interventionist responses such as limiting tourist access to apes, community health programs, and safety, logistic, and cost issues that constrain the potential of vaccination. PMID:22216162

Uncovering plant-pathogen crosstalk through apoplastic proteomic studies.

PubMed

Delaunois, Bertrand; Jeandet, Philippe; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan; Cordelier, Sylvain

2014-01-01

Plant pathogens have evolved by developing different strategies to infect their host, which in turn have elaborated immune responses to counter the pathogen invasion. The apoplast, including the cell wall and extracellular space outside the plasma membrane, is one of the first compartments where pathogen-host interaction occurs. The plant cell wall is composed of a complex network of polysaccharides polymers and glycoproteins and serves as a natural physical barrier against pathogen invasion. The apoplastic fluid, circulating through the cell wall and intercellular spaces, provides a means for delivering molecules and facilitating intercellular communications. Some plant-pathogen interactions lead to plant cell wall degradation allowing pathogens to penetrate into the cells. In turn, the plant immune system recognizes microbial- or damage-associated molecular patterns (MAMPs or DAMPs) and initiates a set of basal immune responses, including the strengthening of the plant cell wall. The establishment of defense requires the regulation of a wide variety of proteins that are involved at different levels, from receptor perception of the pathogen via signaling mechanisms to the strengthening of the cell wall or degradation of the pathogen itself. A fine regulation of apoplastic proteins is therefore essential for rapid and effective pathogen perception and for maintaining cell wall integrity. This review aims to provide insight into analyses using proteomic approaches of the apoplast to highlight the modulation of the apoplastic protein patterns during pathogen infection and to unravel the key players involved in plant-pathogen interaction.

Multiple approaches to assess the safety of artisanal marine food in a tropical estuary.

PubMed

Padovan, A C; Neave, M J; Munksgaard, N C; Gibb, K S

2017-03-01

In this study, metal and metalloid concentrations and pathogens were measured in shellfish at different locations in a tropical estuary, including sites impacted by sewage and industry. Oyster, mangrove snails and mud snails did not exceed Australian and New Zealand Food Standards maximum levels for copper, lead or estimated inorganic arsenic at any site although copper concentrations in oysters and mud snails exceeded generally expected levels at some locations. Bacterial community composition in shellfish was species-specific regardless of location and different to the surrounding water and sediment. In the snails Telescopium telescopium, Terebralia palustris and Nerita balteata, some bacterial taxa differed between sites, but not in Saccostrea cucullata oysters. The abundance of potential human pathogens was very low and pathogen abundance or diversity was not associated with site classification, i.e. sewage impact, industry impact and reference.

Impact of the implementation of rest days in live bird markets on the dynamics of H5N1 highly pathogenic avian influenza.

PubMed

Fournié, G; Guitian, F J; Mangtani, P; Ghani, A C

2011-08-07

Live bird markets (LBMs) act as a network 'hub' and potential reservoir of infection for domestic poultry. They may therefore be responsible for sustaining H5N1 highly pathogenic avian influenza (HPAI) virus circulation within the poultry sector, and thus a suitable target for implementing control strategies. We developed a stochastic transmission model to understand how market functioning impacts on the transmission dynamics. We then investigated the potential for rest days-periods during which markets are emptied and disinfected-to modulate the dynamics of H5N1 HPAI within the poultry sector using a stochastic meta-population model. Our results suggest that under plausible parameter scenarios, HPAI H5N1 could be sustained silently within LBMs with the time spent by poultry in markets and the frequency of introduction of new susceptible birds' dominant factors determining sustained silent spread. Compared with interventions applied in farms (i.e. stamping out, vaccination), our model shows that frequent rest days are an effective means to reduce HPAI transmission. Furthermore, our model predicts that full market closure would be only slightly more effective than rest days to reduce transmission. Strategies applied within markets could thus help to control transmission of the disease.

Impact of the implementation of rest days in live bird markets on the dynamics of H5N1 highly pathogenic avian influenza

PubMed Central

Fournié, G.; Guitian, F. J.; Mangtani, P.; Ghani, A. C.

2011-01-01

Live bird markets (LBMs) act as a network ‘hub’ and potential reservoir of infection for domestic poultry. They may therefore be responsible for sustaining H5N1 highly pathogenic avian influenza (HPAI) virus circulation within the poultry sector, and thus a suitable target for implementing control strategies. We developed a stochastic transmission model to understand how market functioning impacts on the transmission dynamics. We then investigated the potential for rest days—periods during which markets are emptied and disinfected—to modulate the dynamics of H5N1 HPAI within the poultry sector using a stochastic meta-population model. Our results suggest that under plausible parameter scenarios, HPAI H5N1 could be sustained silently within LBMs with the time spent by poultry in markets and the frequency of introduction of new susceptible birds' dominant factors determining sustained silent spread. Compared with interventions applied in farms (i.e. stamping out, vaccination), our model shows that frequent rest days are an effective means to reduce HPAI transmission. Furthermore, our model predicts that full market closure would be only slightly more effective than rest days to reduce transmission. Strategies applied within markets could thus help to control transmission of the disease. PMID:21131332

Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures

PubMed Central

Blanco, Guillermo; Lemus, Jesús A.

2010-01-01

There is increasing concern about the impact of veterinary drugs and livestock pathogens as factors damaging wildlife health, especially of threatened avian scavengers feeding upon medicated livestock carcasses. We conducted a comprehensive study of failed eggs and dead nestlings in bearded vultures (Gypaetus barbatus) to attempt to elucidate the proximate causes of breeding failure behind the recent decline in productivity in the Spanish Pyrenees. We found high concentrations of multiple veterinary drugs, primarily fluoroquinolones, in most failed eggs and nestlings, associated with multiple internal organ damage and livestock pathogens causing disease, especially septicaemia by swine pathogens and infectious bursal disease. The combined impact of drugs and disease as stochastic factors may result in potentially devastating effects exacerbating an already high risk of extinction and should be considered in current conservation programs for bearded vultures and other scavenger species, especially in regards to dangerous veterinary drugs and highly pathogenic poultry viruses. PMID:21152405

Food Safety Impacts from Post-Harvest Processing Procedures of Molluscan Shellfish.

PubMed

Baker, George L

2016-04-18

Post-harvest Processing (PHP) methods are viable food processing methods employed to reduce human pathogens in molluscan shellfish that would normally be consumed raw, such as raw oysters on the half-shell. Efficacy of human pathogen reduction associated with PHP varies with respect to time, temperature, salinity, pressure, and process exposure. Regulatory requirements and PHP molluscan shellfish quality implications are major considerations for PHP usage. Food safety impacts associated with PHP of molluscan shellfish vary in their efficacy and may have synergistic outcomes when combined. Further research for many PHP methods are necessary and emerging PHP methods that result in minimal quality loss and effective human pathogen reduction should be explored.

The Immune System Game

ERIC Educational Resources Information Center

Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

2015-01-01

We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective

PubMed Central

Martínez-Chavarría, Luary C.; Vadyvaloo, Viveka

2015-01-01

Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens. PMID:26441890

The biology, identification and management of Rhizoctonia pathogens

USDA-ARS?s Scientific Manuscript database

Rhizoctonia solani is an economically important soilborne pathogen causing economic losses to crops, vegetables, ornamentals, forest trees and turfgrasses. The pathogenic isolates may belong to diverse genera and species and are variously responsible for pre- or post-emergence damping off of seedlin...

Proteome changes in platelets after pathogen inactivation--an interlaboratory consensus.

PubMed

Prudent, Michel; D'Alessandro, Angelo; Cazenave, Jean-Pierre; Devine, Dana V; Gachet, Christian; Greinacher, Andreas; Lion, Niels; Schubert, Peter; Steil, Leif; Thiele, Thomas; Tissot, Jean-Daniel; Völker, Uwe; Zolla, Lello

2014-04-01

Pathogen inactivation (PI) of platelet concentrates (PCs) reduces the proliferation/replication of a large range of bacteria, viruses, and parasites as well as residual leucocytes. Pathogen-inactivated PCs were evaluated in various clinical trials showing their efficacy and safety. Today, there is some debate over the hemostatic activity of treated PCs as the overall survival of PI platelets seems to be somewhat reduced, and in vitro measurements have identified some alterations in platelet function. Although the specific lesions resulting from PI of PCs are still not fully understood, proteomic studies have revealed potential damages at the protein level. This review merges the key findings of the proteomic analyses of PCs treated by the Mirasol Pathogen Reduction Technology, the Intercept Blood System, and the Theraflex UV-C system, respectively, and discusses the potential impact on the biological functions of platelets. The complementarities of the applied proteomic approaches allow the coverage of a wide range of proteins and provide a comprehensive overview of PI-mediated protein damage. It emerges that there is a relatively weak impact of PI on the overall proteome of platelets. However, some data show that the different PI treatments lead to an acceleration of platelet storage lesions, which is in agreement with the current model of platelet storage lesion in pathogen-inactivated PCs. Overall, the impact of the PI treatment on the proteome appears to be different among the PI systems. Mirasol impacts adhesion and platelet shape change, whereas Intercept seems to impact proteins of intracellular platelet activation pathways. Theraflex influences platelet shape change and aggregation, but the data reported to date are limited. This information provides the basis to understand the impact of different PI on the molecular mechanisms of platelet function. Moreover, these data may serve as basis for future developments of PI technologies for PCs. Further studies should address the impact of both the PI and the storage duration on platelets in PCs because PI may enable the extension of the shelf life of PCs by reducing the bacterial contamination risk. Copyright © 2014 Elsevier Inc. All rights reserved.

Plant innate immunity: an updated insight into defense mechanism.

PubMed

Muthamilarasan, Mehanathan; Prasad, Manoj

2013-06-01

Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and effector-triggered immunity (ETI). MTI confers basal resistance, while ETI confers durable resistance, often resulting in hypersensitive response. Plants also possess systemic acquired resistance (SAR), which provides long-term defense against a broad-spectrum of pathogens. Salicylic-acid-mediated systemic acquired immunity provokes the defense response throughout the plant system during pathogen infection at a particular site. Trans-generational immune priming allows the plant to heritably shield their progeny towards pathogens previously encountered. Plants circumvent the viral infection through RNA interference phenomena by utilizing small RNAs. This review summarizes the molecular mechanisms of plant immune system, and the latest breakthroughs reported in plant defense. We discuss the plant–pathogen interactions and integrated defense responses in the context of presenting an integral understanding in plant molecular immunity.

Limiting damage during infection: lessons from infection tolerance for novel therapeutics.

PubMed

Vale, Pedro F; Fenton, Andy; Brown, Sam P

2014-01-01

The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens (‘‘damage limitation’’)rather than reducing pathogen burdens directly (‘‘pathogen elimination’’). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue,we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of ‘‘evolution-proof’’ anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination.

Exploring the Association between Alzheimer's Disease, Oral Health, Microbial Endocrinology and Nutrition.

PubMed

Harding, Alice; Gonder, Ulrike; Robinson, Sarita J; Crean, StJohn; Singhrao, Sim K

2017-01-01

Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer's disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis , a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host's inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual's diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns. This review suggests healthy diet based interventions that together with improved life style/behavioral changes may reduce and/or delay the incidence of AD.

Rapid Response to Evaluate the Presence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Wild Amphibian Populations in Madagascar

PubMed Central

Kolby, Jonathan E.; Smith, Kristine M.; Ramirez, Sara D.; Rabemananjara, Falitiana; Pessier, Allan P.; Brunner, Jesse L.; Goldberg, Caren S.; Berger, Lee; Skerratt, Lee F.

2015-01-01

We performed a rapid response investigation to evaluate the presence and distribution of amphibian pathogens in Madagascar following our identification of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and ranavirus in commercially exported amphibians. This targeted risk-based field surveillance program was conducted from February to April 2014 encompassing 12 regions and 47 survey sites. We simultaneously collected amphibian and environmental samples to increase survey sensitivity and performed sampling both in wilderness areas and commercial amphibian trade facilities. Bd was not detected in any of 508 amphibian skin swabs or 68 water filter samples, suggesting pathogen prevalence was below 0.8%, with 95% confidence during our visit. Ranavirus was detected in 5 of 97 amphibians, including one adult Mantidactylus cowanii and three unidentified larvae from Ranomafana National Park, and one adult Mantidactylus mocquardi from Ankaratra. Ranavirus was also detected in water samples collected from two commercial amphibian export facilities. We also provide the first report of an amphibian mass-mortality event observed in wild amphibians in Madagascar. Although neither Bd nor ranavirus appeared widespread in Madagascar during this investigation, additional health surveys are required to disentangle potential seasonal variations in pathogen abundance and detectability from actual changes in pathogen distribution and rates of spread. Accordingly, our results should be conservatively interpreted until a comparable survey effort during winter months has been performed. It is imperative that biosecurity practices be immediately adopted to limit the unintentional increased spread of disease through the movement of contaminated equipment or direct disposal of contaminated material from wildlife trade facilities. The presence of potentially introduced strains of ranaviruses suggests that Madagascar's reptile species might also be threatened by disease. Standardized population monitoring of key amphibian and reptile species should be established with urgency to enable early detection of potential impacts of disease emergence in this global biodiversity hotspot. PMID:26083349

Exploring the Association between Alzheimer’s Disease, Oral Health, Microbial Endocrinology and Nutrition

PubMed Central

Harding, Alice; Gonder, Ulrike; Robinson, Sarita J.; Crean, StJohn; Singhrao, Sim K.

2017-01-01

Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer’s disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host’s inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual’s diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns. This review suggests healthy diet based interventions that together with improved life style/behavioral changes may reduce and/or delay the incidence of AD. PMID:29249963

Rapid Response to Evaluate the Presence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Wild Amphibian Populations in Madagascar.

PubMed

Kolby, Jonathan E; Smith, Kristine M; Ramirez, Sara D; Rabemananjara, Falitiana; Pessier, Allan P; Brunner, Jesse L; Goldberg, Caren S; Berger, Lee; Skerratt, Lee F

2015-01-01

We performed a rapid response investigation to evaluate the presence and distribution of amphibian pathogens in Madagascar following our identification of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and ranavirus in commercially exported amphibians. This targeted risk-based field surveillance program was conducted from February to April 2014 encompassing 12 regions and 47 survey sites. We simultaneously collected amphibian and environmental samples to increase survey sensitivity and performed sampling both in wilderness areas and commercial amphibian trade facilities. Bd was not detected in any of 508 amphibian skin swabs or 68 water filter samples, suggesting pathogen prevalence was below 0.8%, with 95% confidence during our visit. Ranavirus was detected in 5 of 97 amphibians, including one adult Mantidactylus cowanii and three unidentified larvae from Ranomafana National Park, and one adult Mantidactylus mocquardi from Ankaratra. Ranavirus was also detected in water samples collected from two commercial amphibian export facilities. We also provide the first report of an amphibian mass-mortality event observed in wild amphibians in Madagascar. Although neither Bd nor ranavirus appeared widespread in Madagascar during this investigation, additional health surveys are required to disentangle potential seasonal variations in pathogen abundance and detectability from actual changes in pathogen distribution and rates of spread. Accordingly, our results should be conservatively interpreted until a comparable survey effort during winter months has been performed. It is imperative that biosecurity practices be immediately adopted to limit the unintentional increased spread of disease through the movement of contaminated equipment or direct disposal of contaminated material from wildlife trade facilities. The presence of potentially introduced strains of ranaviruses suggests that Madagascar's reptile species might also be threatened by disease. Standardized population monitoring of key amphibian and reptile species should be established with urgency to enable early detection of potential impacts of disease emergence in this global biodiversity hotspot.

Combined enzymatic and metabolic analysis of grapevine cell responses to elicitors.

PubMed

Krzyzaniak, Yuko; Negrel, Jonathan; Lemaitre-Guillier, Christelle; Clément, Gilles; Mouille, Grégory; Klinguer, Agnès; Trouvelot, Sophie; Héloir, Marie-Claire; Adrian, Marielle

2018-02-01

Elicitors trigger plant defense responses, including phytoalexin production and cell-wall reinforcement. Primary metabolism plays an important role in these responses as it fuels the associated energetic costs and provides precursors for the synthesis of the numerous secondary metabolites involved in defenses against pathogens. In this context, we aimed to determine whether oligosaccharidic elicitors differing in their capacity to activate defense-associated secondary metabolism in grapevine would differently impact primary metabolism. To answer this question, cell suspensions were treated with two elicitors: an oligogalacturonide, and the β-glucan laminarin. Enzymatic activity assays together with targeted (HPLC) and global (GC-MS) analyses of metabolites were next performed to compare their impact on plant primary or secondary metabolism. The results showed that the oligogalacturonide, which induced the highest level of the phytoalexin resveratrol and the highest activity of stilbene synthase, also induced the highest activity of shikimate hydroxycinnamoyltransferase, a key enzyme involved in the synthesis of lignin. The oligogalacturonide-induced defenses had a significant impact on primary metabolism 24 h following elicitor treatment, with a reduced abundance of pyruvate and 2-oxoglutarate, together with an increase of a set of metabolites including carbohydrates and amino acids. Interestingly, an accumulation of galacturonate and gentiobiose was observed in the oligogalacturonide- and laminarin-treated cells, respectively, suggesting that both elicitors are rapidly hydrolyzed in grapevine cell suspension cultures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Discriminating fever behavior in house flies.

PubMed

Anderson, Robert D; Blanford, Simon; Jenkins, Nina E; Thomas, Matthew B

2013-01-01

Fever has generally been shown to benefit infected hosts. However, fever temperatures also carry costs. While endotherms are able to limit fever costs physiologically, the means by which behavioral thermoregulators constrain these costs are less understood. Here we investigated the behavioral fever response of house flies (Musca domestica L.) challenged with different doses of the fungal entomopathogen, Beauveria bassiana. Infected flies invoked a behavioral fever selecting the hottest temperature early in the day and then moving to cooler temperatures as the day progressed. In addition, flies infected with a higher dose of fungus exhibited more intense fever responses. These variable patterns of fever are consistent with the observation that higher fever temperatures had greater impact on fungal growth. The results demonstrate the capacity of insects to modulate the degree and duration of the fever response depending on the severity of the pathogen challenge and in so doing, balance the costs and benefits of fever.

The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces

PubMed Central

Statovci, Donjete; Aguilera, Mònica; MacSharry, John; Melgar, Silvia

2017-01-01

Recent findings point toward diet having a major impact on human health. Diets can either affect the gut microbiota resulting in alterations in the host’s physiological responses or by directly targeting the host response. The microbial community in the mammalian gut is a complex and dynamic system crucial for the development and maturation of both systemic and mucosal immune responses. Therefore, the complex interaction between available nutrients, the microbiota, and the immune system are central regulators in maintaining homeostasis and fighting against invading pathogens at mucosal sites. Westernized diet, defined as high dietary intake of saturated fats and sucrose and low intake of fiber, represent a growing health risk contributing to the increased occurrence of metabolic diseases, e.g., diabetes and obesity in countries adapting a westernized lifestyle. Inflammatory bowel diseases (IBD) and asthma are chronic mucosal inflammatory conditions of unknown etiology with increasing prevalence worldwide. These conditions have a multifactorial etiology including genetic factors, environmental factors, and dysregulated immune responses. Their increased prevalence cannot solely be attributed to genetic considerations implying that other factors such as diet can be a major contributor. Recent reports indicate that the gut microbiota and modifications thereof, due to a consumption of a diet high in saturated fats and low in fibers, can trigger factors regulating the development and/or progression of both conditions. While asthma is a disease of the airways, increasing evidence indicates a link between the gut and airways in disease development. Herein, we provide a comprehensive review on the impact of westernized diet and associated nutrients on immune cell responses and the microbiota and how these can influence the pathology of IBD and asthma. PMID:28804483

Progress in understanding the immunopathogenesis of psoriasis

PubMed Central

Mak, R.K.H.; Hundhausen, C.; Nestle, F.O.

2010-01-01

This review emphasizes how translation from bench research to clinical knowledge and vice versa has resulted in considerable progress in understanding the immunopathogenesis of psoriasis. First, the journey in understanding the pathogenic mechanisms behind psoriasis is described. The roles of different components of the adaptive and innate immune systems involved in driving the inflammatory response are explained. Discovery of new immune pathways i.e. the IL23/Th17 axis and its subsequent impact on the development of novel biological therapies is highlighted. Identification of potential targets warranting further research for future therapeutic development are also discussed. PMID:20096156

The Use of Filter-feeders to Manage Disease in a Changing World.

PubMed

Burge, Colleen A; Closek, Collin J; Friedman, Carolyn S; Groner, Maya L; Jenkins, Cody M; Shore-Maggio, Amanda; Welsh, Jennifer E

2016-10-01

Rapid environmental change is linked to increases in aquatic disease heightening the need to develop strategies to manage disease. Filter-feeding species are effective biofilters and can naturally mitigate disease risk to humans and wildlife. We review the role of filter-feeders, with an emphasis on bivalves, in altering disease outcomes via augmentation and reduction. Filtration can reduce transmission by removing pathogens from the water column via degradation and release of pathogens in pseudofeces. In other cases, filtration can increase pathogen transmission and disease risk. The effect of filtration on pathogen transmission depends on the selectivity of the filter-feeder, the degree of infectivity by the pathogen, the mechanism(s) of pathogen transmission and the ability of the pathogen to resist degradation. For example, some bacteria and viruses can resist degradation and accumulate within a filter-feeder leading to disease transmission to humans and other wildlife upon ingestion. Since bivalves can concentrate microorganisms, they are also useful as sentinels for the presence of pathogenic microorganisms. While somewhat less studied, other invertebrates, including ascidians and sponges may also provide ecosystem services by altering pathogen transmission. In all scenarios, climate change may affect the potential for filter-feeders to mitigate disease risk. We conclude that an assessment including empirical data and modeling of system-wide impacts should be conducted before selection of filter-feeders to mitigate disease. Such studies should consider physiology of the host and microbe and risk factors for negative impacts including augmentation of other pathogens. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

A saponin-detoxifying enzyme mediates suppression of plant defences

NASA Astrophysics Data System (ADS)

Bouarab, K.; Melton, R.; Peart, J.; Baulcombe, D.; Osbourn, A.

2002-08-01

Plant disease resistance can be conferred by constitutive features such as structural barriers or preformed antimicrobial secondary metabolites. Additional defence mechanisms are activated in response to pathogen attack and include localized cell death (the hypersensitive response). Pathogens use different strategies to counter constitutive and induced plant defences, including degradation of preformed antimicrobial compounds and the production of molecules that suppress induced plant defences. Here we present evidence for a two-component process in which a fungal pathogen subverts the preformed antimicrobial compounds of its host and uses them to interfere with induced defence responses. Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying enzyme. The degradation product of this hydrolysis then suppresses induced defence responses by interfering with fundamental signal transduction processes leading to disease resistance.

Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins.

PubMed

Hoppe, T; Kraus, D; Novak, N; Probstmeier, R; Frentzen, M; Wenghoefer, M; Jepsen, S; Winter, J

2016-10-01

The impact of oral pathogens onto the generation and variability of oral tumors has only recently been investigated. To get further insights, oral cancer cells were treated with pathogens and additionally, as a result of this bacterial cellular infection, with human defensins, which are as anti-microbial peptide members of the innate immune system. After cell stimulation, proliferation behavior, expression analysis of oncogenic relevant defensin genes, and effects on EGFR signaling were investigated. The expression of oncogenic relevant anti-microbial peptides was analyzed with real-time PCR and immunohistochemistry. Cell culture experiments were performed to examine cellular impacts caused by stimulation, i.e., altered gene expression, proliferation rate, and EGF receptor-dependent signaling. Incubation of oral tumor cells with an oral pathogen (Porphyromonas gingivalis) and human α-defensins led to an increase in cell proliferation. In contrast, another oral bacterium used, Aggregatibacter actinomycetemcomitans, enhanced cell death. The bacteria and anti-microbial peptides exhibited diverse effects on the transcript levels of oncogenic relevant defensin genes and epidermal growth factor receptor signaling. These two oral pathogens exhibited opposite primary effects on the proliferation behavior of oral tumor cells. Nevertheless, both microbe species led to similar secondary impacts on the proliferation rate by modifying expression levels of oncogenic relevant α-defensin genes. In this respect, oral pathogens exerted multiplying effects on tumor cell proliferation. Additionally, human defensins were shown to differently influence epidermal growth factor receptor signaling, supporting the hypothesis that these anti-microbial peptides serve as ligands of EGFR, thus modifying the proliferation behavior of oral tumor cells.

Effects of an invasive forest pathogen on abundance of ticks and their vertebrate hosts in a California Lyme disease focus.

PubMed

Swei, Andrea; Ostfeld, Richard S; Lane, Robert S; Briggs, Cheryl J

2011-05-01

Invasive species, including pathogens, can have important effects on local ecosystems, including indirect consequences on native species. This study focuses on the effects of an invasive plant pathogen on a vertebrate community and Ixodes pacificus, the vector of the Lyme disease pathogen (Borrelia burgdorferi) in California. Phytophthora ramorum, the causative agent of sudden oak death, is a non-native pathogen killing trees in California and Oregon. We conducted a multi-year study using a gradient of SOD-caused disturbance to assess the impact on the dusky-footed woodrat (Neotoma fuscipes) and the deer mouse (Peromyscus maniculatus), two reservoir hosts of B. burgdorferi, as well as the impact on the Columbian black-tailed deer (Odocoileus hemionus columbianus) and the western fence lizard (Sceloporus occidentalis), both of which are important hosts for I. pacificus but are not pathogen reservoirs. Abundances of P. maniculatus and S. occidentalis were positively correlated with greater SOD disturbance, whereas N. fuscipes abundance was negatively correlated. We did not find a change in space use by O. hemionus. Our data show that SOD has a positive impact on the density of nymphal ticks, which is expected to increase the risk of human exposure to Lyme disease all else being equal. A positive correlation between SOD disturbance and the density of nymphal ticks was expected given increased abundances of two important hosts: deer mice and western fence lizards. However, further research is needed to integrate the direct effects of SOD on ticks, for example via altered abiotic conditions with host-mediated indirect effects.

An Update on Host-Pathogen Interplay and Modulation of Immune Responses during Orientia tsutsugamushi Infection.

PubMed

Díaz, Fabián E; Abarca, Katia; Kalergis, Alexis M

2018-04-01

The obligate intracellular bacterium Orientia tsutsugamushi is the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions of O. tsutsugamushi , including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models. Copyright © 2018 American Society for Microbiology.

The 'Green Revolution' dwarfing genes play a role in disease resistance in Triticum aestivum and Hordeum vulgare.

PubMed

Saville, R J; Gosman, N; Burt, C J; Makepeace, J; Steed, A; Corbitt, M; Chandler, E; Brown, J K M; Boulton, M I; Nicholson, P

2012-02-01

The Green Revolution dwarfing genes, Rht-B1b and Rht-D1b, encode mutant forms of DELLA proteins and are present in most modern wheat varieties. DELLA proteins have been implicated in the response to biotic stress in the model plant, Arabidopsis thaliana. Using defined wheat Rht near-isogenic lines and barley Sln1 gain of function (GoF) and loss of function (LoF) lines, the role of DELLA in response to biotic stress was investigated in pathosystems representing contrasting trophic styles (biotrophic, hemibiotrophic, and necrotrophic). GoF mutant alleles in wheat and barley confer a resistance trade-off with increased susceptibility to biotrophic pathogens and increased resistance to necrotrophic pathogens whilst the converse was conferred by a LoF mutant allele. The polyploid nature of the wheat genome buffered the effect of single Rht GoF mutations relative to barley (diploid), particularly in respect of increased susceptibility to biotrophic pathogens. A role for DELLA in controlling cell death responses is proposed. Similar to Arabidopsis, a resistance trade-off to pathogens with contrasting pathogenic lifestyles has been identified in monocotyledonous cereal species. Appreciation of the pleiotropic role of DELLA in biotic stress responses in cereals has implications for plant breeding.

The ‘Green Revolution’ dwarfing genes play a role in disease resistance in Triticum aestivum and Hordeum vulgare

PubMed Central

Saville, R. J.; Gosman, N.; Burt, C. J.; Makepeace, J.; Steed, A.; Corbitt, M.; Chandler, E.; Brown, J. K. M.; Boulton, M. I.; Nicholson, P.

2012-01-01

The Green Revolution dwarfing genes, Rht-B1b and Rht-D1b, encode mutant forms of DELLA proteins and are present in most modern wheat varieties. DELLA proteins have been implicated in the response to biotic stress in the model plant, Arabidopsis thaliana. Using defined wheat Rht near-isogenic lines and barley Sln1 gain of function (GoF) and loss of function (LoF) lines, the role of DELLA in response to biotic stress was investigated in pathosystems representing contrasting trophic styles (biotrophic, hemibiotrophic, and necrotrophic). GoF mutant alleles in wheat and barley confer a resistance trade-off with increased susceptibility to biotrophic pathogens and increased resistance to necrotrophic pathogens whilst the converse was conferred by a LoF mutant allele. The polyploid nature of the wheat genome buffered the effect of single Rht GoF mutations relative to barley (diploid), particularly in respect of increased susceptibility to biotrophic pathogens. A role for DELLA in controlling cell death responses is proposed. Similar to Arabidopsis, a resistance trade-off to pathogens with contrasting pathogenic lifestyles has been identified in monocotyledonous cereal species. Appreciation of the pleiotropic role of DELLA in biotic stress responses in cereals has implications for plant breeding. PMID:22090435

Death don't have no mercy and neither does calcium: Arabidopsis CYCLIC NUCLEOTIDE GATED CHANNEL2 and innate immunity.

PubMed

Ali, Rashid; Ma, Wei; Lemtiri-Chlieh, Fouad; Tsaltas, Dimitrios; Leng, Qiang; von Bodman, Susannne; Berkowitz, Gerald A

2007-03-01

Plant innate immune response to pathogen infection includes an elegant signaling pathway leading to reactive oxygen species generation and resulting hypersensitive response (HR); localized programmed cell death in tissue surrounding the initial infection site limits pathogen spread. A veritable symphony of cytosolic signaling molecules (including Ca(2+), nitric oxide [NO], cyclic nucleotides, and calmodulin) have been suggested as early components of HR signaling. However, specific interactions among these cytosolic secondary messengers and their roles in the signal cascade are still unclear. Here, we report some aspects of how plants translate perception of a pathogen into a signal cascade leading to an innate immune response. We show that Arabidopsis thaliana CYCLIC NUCLEOTIDE GATED CHANNEL2 (CNGC2/DND1) conducts Ca(2+) into cells and provide a model linking this Ca(2+) current to downstream NO production. NO is a critical signaling molecule invoking plant innate immune response to pathogens. Plants without functional CNGC2 lack this cell membrane Ca(2+) current and do not display HR; providing the mutant with NO complements this phenotype. The bacterial pathogen-associated molecular pattern elicitor lipopolysaccharide activates a CNGC Ca(2+) current, which may be linked to NO generation due to buildup of cytosolic Ca(2+)/calmodulin.

[Saccharomyces boulardii CNCM I-745 influences the gut-associated immune system].

PubMed

Stier, Heike; Bischoff, Stephan C

2017-06-01

The impact of the intestinal microbiome is increasing steadily with regard to the immune function und the defense against pathogens. The medicinal yeast Saccharomyces boulardii CNCM I-745 (S. boulardii) has been used as probiotic for the prevention and treatment of infectious diarrhea since more than 50 years. Meta-analyses confirm the clinical efficacy of S. boulardii to treat diarrhea of various origins in children and adults. This review article summarizes experimental studies on molecular and immunological mechanisms which explain the proven clinical efficacy of S. boulardii. Thereby the focus is on the gut-associated immune system. S. boulardii stimulates the release of immunoglobulins and cytokines and also induces the maturation of immune cells. This suggests that S. boulardii is capable of activating the unspecific immune system. In case of an infection, S. boulardii is able to bind pathogenic bacteria and to neutralize their toxins. Moreover, the medicinal yeast can attenuate the overreacting inflammatory immune response, by interfering with the signaling cascade, which is induced by the infection, and that way influences the innate and adaptive immune system. Thanks to these mechanisms the pathogens' potential of adhesion is lessened. Thus the intestinal epithelial layer is protected and diarrhea-induced fluid loss is reduced. The different molecular and immunological mechanisms investigated in the experimental studies prove the already confirmed very good clinical efficacy of S. boulardii in infectious diarrhea caused by pathogens such as bacteria, viruses, and fungi.