Structure of a bacterial type III secretion system in contact with a host membrane in situ

NASA Astrophysics Data System (ADS)

Nans, Andrea; Kudryashev, Mikhail; Saibil, Helen R.; Hayward, Richard D.

2015-12-01

Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform-ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking `pump-action' conformational changes that underpin effector injection.

Structure of a bacterial type III secretion system in contact with a host membrane in situ.

PubMed

Nans, Andrea; Kudryashev, Mikhail; Saibil, Helen R; Hayward, Richard D

2015-12-11

Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform-ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking 'pump-action' conformational changes that underpin effector injection.

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.

Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans.

PubMed

Raj, Shriya; Nazemidashtarjandi, Saeed; Kim, Jihyun; Joffe, Luna; Zhang, Xiaoxue; Singh, Ashutosh; Mor, Visesato; Desmarini, Desmarini; Djordjevic, Julianne; Raleigh, Daniel P; Rodrigues, Marcio L; London, Erwin; Del Poeta, Maurizio; Farnoud, Amir M

2017-11-01

Fungal glucosylceramide (GlcCer) is a plasma membrane sphingolipid in which the sphingosine backbone is unsaturated in carbon position 8 (C8) and methylated in carbon position 9 (C9). Studies in the fungal pathogen, Cryptococcus neoformans, have shown that loss of GlcCer synthase activity results in complete loss of virulence in the mouse model. However, whether the loss of virulence is due to the lack of the enzyme or to the loss of the sphingolipid is not known. In this study, we used genetic engineering to alter the chemical structure of fungal GlcCer and studied its effect on fungal growth and pathogenicity. Here we show that unsaturation in C8 and methylation in C9 is required for virulence in the mouse model without affecting fungal growth in vitro or common virulence factors. However, changes in GlcCer structure led to a dramatic susceptibility to membrane stressors resulting in increased cell membrane permeability and rendering the fungal mutant unable to grow within host macrophages. Biophysical studies using synthetic vesicles containing GlcCer revealed that the saturated and unmethylated sphingolipid formed vesicles with higher lipid order that were more likely to phase separate into ordered domains. Taken together, these studies show for the first time that a specific structure of GlcCer is a major regulator of membrane permeability required for fungal pathogenicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Temporal and spatial scaling of the genetic structure of a vector-borne plant pathogen.

PubMed

Coletta-Filho, Helvécio D; Francisco, Carolina S; Almeida, Rodrigo P P

2014-02-01

The ecology of plant pathogens of perennial crops is affected by the long-lived nature of their immobile hosts. In addition, changes to the genetic structure of pathogen populations may affect disease epidemiology and management practices; examples include local adaptation of more fit genotypes or introduction of novel genotypes from geographically distant areas via human movement of infected plant material or insect vectors. We studied the genetic structure of Xylella fastidiosa populations causing disease in sweet orange plants in Brazil at multiple scales using fast-evolving molecular markers (simple-sequence DNA repeats). Results show that populations of X. fastidiosa were regionally isolated, and that isolation was maintained for populations analyzed a decade apart from each other. However, despite such geographic isolation, local populations present in year 2000 were largely replaced by novel genotypes in 2009 but not as a result of migration. At a smaller spatial scale (individual trees), results suggest that isolates within plants originated from a shared common ancestor. In summary, new insights on the ecology of this economically important plant pathogen were obtained by sampling populations at different spatial scales and two different time points.

Colonization of the Cecal Mucosa by Helicobacter hepaticus Impacts the Diversity of the Indigenous Microbiota

PubMed Central

Kuehl, Carole J.; Wood, Heather D.; Marsh, Terence L.; Schmidt, Thomas M.; Young, Vincent B.

2005-01-01

Establishment of mucosal and/or luminal colonization is the first step in the pathogenesis of many gastrointestinal bacterial pathogens. The pathogen must be able to establish itself in the face of competition from the complex microbial community that is already in place. We used culture-independent methods to monitor the colonization of the cecal mucosa of Helicobacter-free mice following experimental infection with the pathogen Helicobacter hepaticus. Two days after infection, H. hepaticus comprised a minor component of the mucosa-associated microbiota, but within 14 days, it became the dominant member of the community. Colonization of the mucosa by H. hepaticus was associated with a decrease in the overall diversity of the microbial community, in large part due to changes in evenness resulting from the relative dominance of H. hepaticus as a member of the community. Our results demonstrate that invasion of the complex gastrointestinal microbial community by a pathogenic microorganism causes reproducible and significant disturbances in the community structure. The use of non-culture-based methods to monitor these changes should lead to a greater understanding of the ecological principles that govern pathogen invasion and may lead to novel methods for the prevention and control of gastrointestinal pathogens. PMID:16177375

Canopy gaps decrease microbial densities and disease risk for a shade-intolerant tree species

Treesearch

Kurt O. Reinhart; Alejandro A. Royo; Stacie A. Kageyama; Keith. Clay

2010-01-01

Canopy disturbances such as windthrowevents have obvious impacts on forest structure and composition aboveground, but changes in soil microbial communities and the consequences of these changes are less understood.We characterized the densities of a soil-borne pathogenic oomycete (Pythium) and a common saprotrophic zygomycete (Mortierella...

Genotypic diversity of merozoite surface antigen 1 of Babesia bovis within an endemic population.

PubMed

Lau, Audrey O T; Cereceres, Karla; Palmer, Guy H; Fretwell, Debbie L; Pedroni, Monica J; Mosqueda, Juan; McElwain, Terry F

2010-08-01

Multiple genetically distinct strains of a pathogen circulate and compete for dominance within populations of animal reservoir hosts. Understanding the basis for genotypic strain structure is critical for predicting how pathogens respond to selective pressures and how shifts in pathogen population structure can lead to disease outbreaks. Evidence from related Apicomplexans such as Plasmodium, Toxoplasma, Cryptosporidium and Theileria suggests that various patterns of population dynamics exist, including but not limited to clonal, oligoclonal, panmictic and epidemic genotypic strain structures. In Babesia bovis, genetic diversity of variable merozoite surface antigen (VMSA) genes has been associated with disease outbreaks, including in previously vaccinated animals. However, the extent of VMSA diversity within a defined population in an endemic area has not been examined. We analyzed genotypic diversity and temporal change of MSA-1, a member of the VMSA family, in individual infected animals within a reservoir host population. Twenty-eight distinct MSA-1 genotypes were identified within the herd. All genotypically distinct MSA-1 sequences clustered into three groups based on sequence similarity. Two thirds of the animals tested changed their dominant MSA-1 genotypes during a 6-month period. Five animals within the population contained multiple genotypes. Interestingly, the predominant genotypes within those five animals also changed over the 6-month sampling period, suggesting ongoing transmission or emergence of variant MSA-1 genotypes within the herd. This study demonstrated an unexpected level of diversity for a single copy gene in a haploid genome, and illustrates the dynamic genotype structure of B. bovis within an individual animal in an endemic region. Co-infection with multiple diverse MSA-1 genotypes provides a basis for more extensive genotypic shifts that characterizes outbreak strains.

Structures of Cryptococcus neoformans Protein Farnesyltransferase Reveal Strategies for Developing Inhibitors That Target Fungal Pathogens

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

Hast, Michael A.; Nichols, Connie B.; Armstrong, Stephanie M.

Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities andmore » differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.« less

Genetic diversity, structure, and demographic change in tanoak, Lithocarpus densiflorus (Fagaceae), the most susceptible species to sudden oak death in California

Treesearch

A. Nettel; R. S. Dodd; Z. Afzal-Rafii

2009-01-01

Knowledge of population genetic structure of tanoak (Lithocarpus densiflorus) is of interest to pathologists seeking natural variation in resistance to sudden oak death disease, to resource managers who need indications of conservation priorities in this species now threatened by the introduced pathogen (Phytophthora ramorum),...

Membrane rafts in host-pathogen interactions.

PubMed

Riethmüller, Joachim; Riehle, Andrea; Grassmé, Heike; Gulbins, Erich

2006-12-01

Central elements in the infection of mammalian cells with viral, bacterial and parasitic pathogens include the adhesion of the pathogen to surface receptors of the cell, recruitment of additional receptor proteins to the infection-site, a re-organization of the membrane and, in particular, the intracellular signalosome. Internalization of the pathogen results in the formation of a phagosome that is supposed to fuse with lysosomes to form phagolysosomes, which serve the degradation of the pathogen, an event actively prevented by some pathogens. In summary, these changes in the infected cell permit pathogens to trigger apoptosis (for instance of macrophages paralysing the initial immune response), to invade the cell and/or to survive in the cell, but they also serve the mammalian cell to defeat the infection, for instance by activation of transcription factors and the release of cytokines. Distinct membrane domains in the plasma membrane and intracellular vesicles that are mainly composed of sphingolipids and cholesterol or enriched with the sphingolipid ceramide, are critically involved in all of these events occurring during the infection. These membrane structures are therefore very attractive targets for novel drugs to interfere with bacterial, viral and parasitic infections.

Bioinformatics comparisons of RNA-binding proteins of pathogenic and non-pathogenic Escherichia coli strains reveal novel virulence factors.

PubMed

Ghosh, Pritha; Sowdhamini, Ramanathan

2017-08-24

Pathogenic bacteria have evolved various strategies to counteract host defences. They are also exposed to environments that are undergoing constant changes. Hence, in order to survive, bacteria must adapt themselves to the changing environmental conditions by performing regulations at the transcriptional and/or post-transcriptional levels. Roles of RNA-binding proteins (RBPs) as virulence factors have been very well studied. Here, we have used a sequence search-based method to compare and contrast the proteomes of 16 pathogenic and three non-pathogenic E. coli strains as well as to obtain a global picture of the RBP landscape (RBPome) in E. coli. Our results show that there are no significant differences in the percentage of RBPs encoded by the pathogenic and the non-pathogenic E. coli strains. The differences in the types of Pfam domains as well as Pfam RNA-binding domains, encoded by these two classes of E. coli strains, are also insignificant. The complete and distinct RBPome of E. coli has been established by studying all known E. coli strains till date. We have also identified RBPs that are exclusive to pathogenic strains, and most of them can be exploited as drug targets since they appear to be non-homologous to their human host proteins. Many of these pathogen-specific proteins were uncharacterised and their identities could be resolved on the basis of sequence homology searches with known proteins. Detailed structural modelling, molecular dynamics simulations and sequence comparisons have been pursued for selected examples to understand differences in stability and RNA-binding. The approach used in this paper to cross-compare proteomes of pathogenic and non-pathogenic strains may also be extended to other bacterial or even eukaryotic proteomes to understand interesting differences in their RBPomes. The pathogen-specific RBPs reported in this study, may also be taken up further for clinical trials and/or experimental validations.

Structural Effects of Fibulin 5 Missense Mutations Associated with Age-Related Macular Degeneration and Cutis Laxa

PubMed Central

Jones, Richard P. O.; Ridley, Caroline; Jowitt, Thomas A.; Wang, Ming-Chuan; Howard, Marjorie; Bobola, Nicoletta; Wang, Tao; Bishop, Paul N.; Kielty, Cay M.; Baldock, Clair; Lotery, Andrew J.; Trump, Dorothy

2010-01-01

Purpose. AMD has a complex etiology with environmental and genetic risk factors. Ten fibulin 5 sequence variants have been associated with AMD and two other fibulin 5 mutations cause autosomal-recessive cutis laxa. Fibulin 5 is a 52-kDa calcium-binding epidermal growth factor (cbEGF)–rich extracellular matrix protein that is essential for the formation of elastic tissues. Biophysical techniques were used to detect structural changes in the fibulin 5 mutants and to determine whether changes are predictive of pathogenicity. Methods. Native PAGE, nonreduced SDS-PAGE, size-exclusion column multiangle laser light scattering, sedimentation velocity, and circular dichroism (CD) were used to investigate the mobility, hydrodynamic radii, folding, and oligomeric states of the fibulin 5 mutants in the absence and presence of Ca2+. Results. CD showed that all mutants are folded, although perturbations to secondary structure contents were detected. Both cutis laxa mutants increased dimerization. Most other mutants slightly increased self-association in the absence of Ca2+ but this was also demonstrated by G202R, a polymorphism detected in a control individual. The AMD-associated mutant G412E showed lower-than-expected mobility during native-PAGE, the largest hydrodynamic radius for the monomer form and the highest levels of aggregation in both the absence and presence of Ca2+. Conclusions. The results identified structural differences for the disease-causing cutis laxa mutants and for one AMD variant (G412E), suggesting that this may also be pathogenic. Although the other AMD-associated mutants showed no gross structural differences, they cannot be excluded as pathogenic by differences outside the scope of this study—for example, disruption of heterointeractions. PMID:20007835

Local interactions lead to pathogen-driven change to host population dynamics.

PubMed

Boots, Michael; Childs, Dylan; Reuman, Daniel C; Mealor, Michael

2009-10-13

Individuals tend to interact more strongly with nearby individuals or within particular social groups. Recent theoretical advances have demonstrated that these within-population relationships can have fundamental implications for ecological and evolutionary dynamics. In particular, contact networks are crucial to the spread and evolution of disease. However, the theory remains largely untested experimentally. Here, we manipulate habitat viscosity and thereby the frequency of local interactions in an insect-pathogen model system in which the virus had previously been shown to have little effect on host population dynamics. At high viscosity, the pathogen caused the collapse of dominant and otherwise stable host generation cycles. Modeling shows that this collapse can be explained by an increase in the frequency of intracohort interactions relative to intercohort interactions, leading to more disease transmission. Our work emphasizes that spatial structure can subtly mediate intraspecific competition and the effects of natural enemies. A decrease in dispersal in a population may actually (sometimes rather counterintuitively) intensify the effects of parasites. Broadly, because anthropological and environmental change often cause changes in population mixing, our work highlights the potential for dramatic changes in the effects of parasites on host populations.

Frontiers in research on biodiversity and disease.

PubMed

Johnson, Pieter T J; Ostfeld, Richard S; Keesing, Felicia

2015-10-01

Global losses of biodiversity have galvanised efforts to understand how changes to communities affect ecological processes, including transmission of infectious pathogens. Here, we review recent research on diversity-disease relationships and identify future priorities. Growing evidence from experimental, observational and modelling studies indicates that biodiversity changes alter infection for a range of pathogens and through diverse mechanisms. Drawing upon lessons from the community ecology of free-living organisms, we illustrate how recent advances from biodiversity research generally can provide necessary theoretical foundations, inform experimental designs, and guide future research at the interface between infectious disease risk and changing ecological communities. Dilution effects are expected when ecological communities are nested and interactions between the pathogen and the most competent host group(s) persist or increase as biodiversity declines. To move beyond polarising debates about the generality of diversity effects and develop a predictive framework, we emphasise the need to identify how the effects of diversity vary with temporal and spatial scale, to explore how realistic patterns of community assembly affect transmission, and to use experimental studies to consider mechanisms beyond simple changes in host richness, including shifts in trophic structure, functional diversity and symbiont composition. © 2015 John Wiley & Sons Ltd/CNRS.

Frontiers in research on biodiversity and disease

PubMed Central

Johnson, Pieter T. J.; Ostfeld, Richard S.; Keesing, Felicia

2016-01-01

Global losses of biodiversity have galvanised efforts to understand how changes to communities affect ecological processes, including transmission of infectious pathogens. Here, we review recent research on diversity–disease relationships and identify future priorities. Growing evidence from experimental, observational and modelling studies indicates that biodiversity changes alter infection for a range of pathogens and through diverse mechanisms. Drawing upon lessons from the community ecology of free-living organisms, we illustrate how recent advances from biodiversity research generally can provide necessary theoretical foundations, inform experimental designs, and guide future research at the interface between infectious disease risk and changing ecological communities. Dilution effects are expected when ecological communities are nested and interactions between the pathogen and the most competent host group(s) persist or increase as biodiversity declines. To move beyond polarising debates about the generality of diversity effects and develop a predictive framework, we emphasise the need to identify how the effects of diversity vary with temporal and spatial scale, to explore how realistic patterns of community assembly affect transmission, and to use experimental studies to consider mechanisms beyond simple changes in host richness, including shifts in trophic structure, functional diversity and symbiont composition. PMID:26261049

Chapter 2: Climate, disturbance, and vulnerability to vegetation change in the Northwest Forest Plan Area

Treesearch

Matthew J. Reilly; Thomas A.  Spies; Ramona Butz Littell; John B. . Kim

2018-01-01

Climate change is expected to alter the composition, structure, and function of forested ecosystems in the United States (Vose et al. 2012). Increases in atmospheric concentrations of greenhouse gases (e.g., carbon dioxide [CO2]) and temperature, as well as altered precipitation and disturbance regimes (e.g., fire, insects, pathogens, and windstorms), are expected to...

Evolution in action: Climate change, biodiversity dynamics and emerging infectious disease

USDA-ARS?s Scientific Manuscript database

Climatological variation and ecological perturbation have been pervasive drivers of faunal assembly, structure and diversification for parasites and pathogens through recurrent events of geographic and host colonization at varying spatial and temporal scales of Earth history. Episodic shifts in clim...

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.

LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

PubMed

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

2016-12-01

To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

Longitudinal Structural changes in Late-onset Retinal Degeneration

PubMed Central

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A.

2016-01-01

Purpose To characterize longitudinal structural changes in early stages of late-onset retinal degeneration (L-ORD) to investigate pathogenic mechanisms. Methods Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence (FAF) images, near infrared reflectance (NIR-R) fundus images, and spectral domain optical coherence tomography (SD-OCT) scans were acquired during follow-up. Results Both patients, aged 45 and 50 years, had good visual acuities (> 20/20 OU) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on FAF and NIR-R imaging. Baseline SD-OCT imaging revealed subretinal deposits that resemble reticular pseudodrusen (RPD) described in age-related macular degeneration (AMD). During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial (RPE) layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt RPE and outer retinal atrophy. Conclusions Structural changes in early stage L-ORD revealed by multimodal imaging resemble those of RPD observed in AMD and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations. PMID:27388725

Yeast cell differentiation: Lessons from pathogenic and non-pathogenic yeasts.

PubMed

Palková, Zdena; Váchová, Libuše

2016-09-01

Yeasts, historically considered to be single-cell organisms, are able to activate different differentiation processes. Individual yeast cells can change their life-styles by processes of phenotypic switching such as the switch from yeast-shaped cells to filamentous cells (pseudohyphae or true hyphae) and the transition among opaque, white and gray cell-types. Yeasts can also create organized multicellular structures such as colonies and biofilms, and the latter are often observed as contaminants on surfaces in industry and medical care and are formed during infections of the human body. Multicellular structures are formed mostly of stationary-phase or slow-growing cells that diversify into specific cell subpopulations that have unique metabolic properties and can fulfill specific tasks. In addition to the development of multiple protective mechanisms, processes of metabolic reprogramming that reflect a changed environment help differentiated individual cells and/or community cell constituents to survive harmful environmental attacks and/or to escape the host immune system. This review aims to provide an overview of differentiation processes so far identified in individual yeast cells as well as in multicellular communities of yeast pathogens of the Candida and Cryptococcus spp. and the Candida albicans close relative, Saccharomyces cerevisiae. Molecular mechanisms and extracellular signals potentially involved in differentiation processes are also briefly mentioned. Copyright © 2016 Elsevier Ltd. All rights reserved.

Social structure, infectious diseases, disasters, secularism, and cultural change in America.

PubMed

Grossmann, Igor; Varnum, Michael E W

2015-03-01

Why do cultures change? The present work examined cultural change in eight cultural-level markers, or correlates, of individualism in the United States, all of which increased over the course of the 20th century: frequency of individualist themes in books, preference for uniqueness in baby naming, frequency of single-child relative to multichild families, frequency of single-generation relative to multigeneration households, percentage of adults and percentage of older adults living alone, small family size, and divorce rates (relative to marriage rates). We tested five key hypotheses regarding cultural change in individualism-collectivism. As predicted by previous theories, changes in socioeconomic structure, pathogen prevalence, and secularism accompanied changes in individualism averaged across all measures. The relationship with changes in individualism was less robust for urbanization. Contrary to previous theories, changes in individualism were positively (as opposed to negatively) related to the frequency of disasters. Time-lagged analyses suggested that only socioeconomic structure had a robust effect on individualism; changes in socioeconomic structure preceded changes in individualism. Implications for anthropology, psychology, and sociology are discussed. © The Author(s) 2015.

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 ...

Pathogenic changes of dispersion and contrast of coherent images of biotissues

NASA Astrophysics Data System (ADS)

Pishak, Olga V.

2002-02-01

The paper presents the results of polarization-correlation investigation of multifractal collagen structure of physiologically normal and pathologically changed tissues of women's reproductive sphere and of skin. The technique of polarization selection of coherent biotissues' images with the following determination of their autocorrelation functions and spectral densities is suggested. The correlation-optical criteria of early diagnostics of pathological changes' appearance of myometry (forming of the germ of fibromyoma) and of skin(psoriasis) are determined. The suggested paper is directed to investigation of the possibilities of pathological changes of biotissues' morphological structure by means of determining the polarizationally filtered autocorrelation functions (ACF) and corresponding spectral densities of their coherent images.

Enteric pathogen-plant interactions: molecular connections leading to colonization and growth and implications for food safety.

PubMed

Martínez-Vaz, Betsy M; Fink, Ryan C; Diez-Gonzalez, Francisco; Sadowsky, Michael J

2014-01-01

Leafy green vegetables have been identified as a source of foodborne illnesses worldwide over the past decade. Human enteric pathogens, such as Escherichia coli O157:H7 and Salmonella, have been implicated in numerous food poisoning outbreaks associated with the consumption of fresh produce. An understanding of the mechanisms responsible for the establishment of pathogenic bacteria in or on vegetable plants is critical for understanding and ameliorating this problem as well as ensuring the safety of our food supply. While previous studies have described the growth and survival of enteric pathogens in the environment and also the risk factors associated with the contamination of vegetables, the molecular events involved in the colonization of fresh produce by enteric pathogens are just beginning to be elucidated. This review summarizes recent findings on the interactions of several bacterial pathogens with leafy green vegetables. Changes in gene expression linked to the bacterial attachment and colonization of plant structures are discussed in light of their relevance to plant-microbe interactions. We propose a mechanism for the establishment and association of enteric pathogens with plants and discuss potential strategies to address the problem of foodborne illness linked to the consumption of leafy green vegetables.

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.

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

Impact of biodiversity and seasonality on Lyme-pathogen transmission.

PubMed

Lou, Yijun; Wu, Jianhong; Wu, Xiaotian

2014-11-28

Lyme disease imposes increasing global public health challenges. To better understand the joint effects of seasonal temperature variation and host community composition on the pathogen transmission, a stage-structured periodic model is proposed by integrating seasonal tick development and activity, multiple host species and complex pathogen transmission routes between ticks and reservoirs. Two thresholds, one for tick population dynamics and the other for Lyme-pathogen transmission dynamics, are identified and shown to fully classify the long-term outcomes of the tick invasion and disease persistence. Seeding with the realistic parameters, the tick reproduction threshold and Lyme disease spread threshold are estimated to illustrate the joint effects of the climate change and host community diversity on the pattern of Lyme disease risk. It is shown that climate warming can amplify the disease risk and slightly change the seasonality of disease risk. Both the "dilution effect" and "amplification effect" are observed by feeding the model with different possible alternative hosts. Therefore, the relationship between the host community biodiversity and disease risk varies, calling for more accurate measurements on the local environment, both biotic and abiotic such as the temperature and the host community composition.

Evaluation of the significance of cell wall polymers in flax infected with a pathogenic strain of Fusarium oxysporum.

PubMed

Wojtasik, Wioleta; Kulma, Anna; Dymińska, Lucyna; Hanuza, Jerzy; Czemplik, Magdalena; Szopa, Jan

2016-03-22

Fusarium oxysporum infection leads to Fusarium-derived wilt, which is responsible for the greatest losses in flax (Linum usitatissimum) crop yield. Plants infected by Fusarium oxysporum show severe symptoms of dehydration due to the growth of the fungus in vascular tissues. As the disease develops, vascular browning and leaf yellowing can be observed. In the case of more virulent strains, plants die. The pathogen's attack starts with secretion of enzymes degrading the host cell wall. The main aim of the study was to evaluate the role of the cell wall polymers in the flax plant response to the infection in order to better understand the process of resistance and develop new ways to protect plants against infection. For this purpose, the expression of genes involved in cell wall polymer metabolism and corresponding polymer levels were investigated in flax seedlings after incubation with Fusarium oxysporum. This analysis was facilitated by selecting two groups of genes responding differently to the infection. The first group comprised genes strongly affected by the infection and activated later (phenylalanine ammonia lyase and glucosyltransferase). The second group comprised genes which are slightly affected (up to five times) and their expression vary as the infection progresses. Fusarium oxysporum infection did not affect the contents of cell wall polymers, but changed their structure. The results suggest that the role of the cell wall polymers in the plant response to Fusarium oxysporum infection is manifested through changes in expression of their genes and rearrangement of the cell wall polymers. Our studies provided new information about the role of cellulose and hemicelluloses in the infection process, the change of their structure and the expression of genes participating in their metabolism during the pathogen infection. We also confirmed the role of pectin and lignin in this process, indicating the major changes at the mRNA level of lignin metabolism genes and the loosening of the pectin structure.

Proteomics of survival structures of fungal pathogens.

PubMed

Loginov, Dmitry; Šebela, Marek

2016-09-25

Fungal pathogens are causal agents of numerous human, animal, and plant diseases. They employ various infection modes to overcome host defense systems. Infection mechanisms of different fungi have been subjected to many comprehensive studies. These investigations have been facilitated by the development of various '-omics' techniques, and proteomics has one of the leading roles in this regard. Fungal conidia and sclerotia could be considered the most important structures for pathogenesis as their germination is one of the first steps towards a host infection. They represent interesting objects for proteomic studies because of the presence of unique proteins with unexplored biotechnological potential required for pathogen viability, development and the subsequent host infection. Proteomic peculiarities of survival structures of different fungi, including those of biotechnological significance (e.g., Asperillus fumigatus, A. nidulans, Metarhizium anisopliae), in a dormant state, as well as changes in the protein production during early stages of fungal development are the subjects of the present review. We focused on biological aspects of proteomic studies of fungal survival structures rather than on an evaluation of proteomic approaches. For that reason, proteins that have been identified in this context are discussed from the point of view of their involvement in different biological processes and possible functions assigned to them. This is the first review paper summarizing recent advances in proteomics of fungal survival structures. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature variation, bacterial diversity and fungal infection dynamics in the amphibian skin.

PubMed

Longo, Ana V; Zamudio, Kelly R

2017-09-01

Host-associated bacterial communities on the skin act as the first line of defence against invading pathogens. Yet, for most natural systems, we lack a clear understanding of how temperature variability affects structure and composition of skin bacterial communities and, in turn, promotes or limits the colonization of opportunistic pathogens. Here, we examine how natural temperature fluctuations might be related to changes in skin bacterial diversity over time in three amphibian populations infected by the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Our focal host species (Eleutherodactylus coqui) is a direct-developing frog that has suffered declines at some populations in the last 20 years, while others have not experienced any changes. We quantified skin bacterial alpha- and beta-diversity at four sampling time points, a period encompassing two seasons and ample variation in natural infections and environmental conditions. Despite the different patterns of infection across populations, we detected an overall increase in bacterial diversity through time, characterized by the replacement of bacterial operational taxonomic units (OTUs). Increased frog body temperatures possibly allowed the colonization of bacteria as well as the recruitment of a subset of indicator OTUs, which could have promoted the observed changes in diversity patterns. Our results suggest that natural environmental fluctuations might be involved in creating opportunities for bacterial replacement, potentially attenuating pathogen transmission and thus contributing to host persistence in E. coqui populations. © 2017 John Wiley & Sons Ltd.

Biocontrol mechanism by root-associated Bacillus amyloliquefaciens FZB42 – a review

PubMed Central

Chowdhury, Soumitra Paul; Hartmann, Anton; Gao, XueWen; Borriss, Rainer

2015-01-01

Bacillus amyloliquefaciens subsp. plantarum FZB42 is a Gram-positive model bacterium for unraveling plant–microbe interactions in Bacilli. In addition, FZB42 is used commercially as biofertilizer and biocontrol agent in agriculture. Genome analysis of FZB42 revealed that nearly 10% of the FZB42 genome is devoted to synthesizing antimicrobial metabolites and their corresponding immunity genes. However, recent investigations in planta demonstrated that – except surfactin – the amount of such compounds found in vicinity of plant roots is relatively low, making doubtful a direct function in suppressing competing microflora including plant pathogens. These metabolites have been also suspected to induce changes within the rhizosphere microbial community, which might affect environment and plant health. However, sequence analysis of rhizosphere samples revealed only marginal changes in the root microbiome, suggesting that secondary metabolites are not the key factor in protecting plants from pathogenic microorganisms. On the other hand, adding FZB42 to plants compensate, at least in part, changes in the community structure caused by the pathogen, indicating an interesting mechanism of plant protection by beneficial Bacilli. Sub-lethal concentrations of cyclic lipopeptides and volatiles produced by plant-associated Bacilli trigger pathways of induced systemic resistance (ISR), which protect plants against attacks of pathogenic microbes, viruses, and nematodes. Stimulation of ISR by bacterial metabolites is likely the main mechanism responsible for biocontrol action of FZB42. PMID:26284057

Biocontrol mechanism by root-associated Bacillus amyloliquefaciens FZB42 - a review.

PubMed

Chowdhury, Soumitra Paul; Hartmann, Anton; Gao, XueWen; Borriss, Rainer

2015-01-01

Bacillus amyloliquefaciens subsp. plantarum FZB42 is a Gram-positive model bacterium for unraveling plant-microbe interactions in Bacilli. In addition, FZB42 is used commercially as biofertilizer and biocontrol agent in agriculture. Genome analysis of FZB42 revealed that nearly 10% of the FZB42 genome is devoted to synthesizing antimicrobial metabolites and their corresponding immunity genes. However, recent investigations in planta demonstrated that - except surfactin - the amount of such compounds found in vicinity of plant roots is relatively low, making doubtful a direct function in suppressing competing microflora including plant pathogens. These metabolites have been also suspected to induce changes within the rhizosphere microbial community, which might affect environment and plant health. However, sequence analysis of rhizosphere samples revealed only marginal changes in the root microbiome, suggesting that secondary metabolites are not the key factor in protecting plants from pathogenic microorganisms. On the other hand, adding FZB42 to plants compensate, at least in part, changes in the community structure caused by the pathogen, indicating an interesting mechanism of plant protection by beneficial Bacilli. Sub-lethal concentrations of cyclic lipopeptides and volatiles produced by plant-associated Bacilli trigger pathways of induced systemic resistance (ISR), which protect plants against attacks of pathogenic microbes, viruses, and nematodes. Stimulation of ISR by bacterial metabolites is likely the main mechanism responsible for biocontrol action of FZB42.

Gene Expression of Type VI Secretion System Associated with Environmental Survival in Acidovorax avenae subsp. avenae by Principle Component Analysis

PubMed Central

Cui, Zhouqi; Jin, Guoqiang; Li, Bin; Kakar, Kaleem Ullah; Ojaghian, Mohammad Reza; Wang, Yangli; Xie, Guanlin; Sun, Guochang

2015-01-01

Valine glycine repeat G (VgrG) proteins are regarded as one of two effectors of Type VI secretion system (T6SS) which is a complex multi-component secretion system. In this study, potential biological roles of T6SS structural and VgrG genes in a rice bacterial pathogen, Acidovorax avenae subsp. avenae (Aaa) RS-1, were evaluated under seven stress conditions using principle component analysis of gene expression. The results showed that growth of the pathogen was reduced by H2O2 and paraquat-induced oxidative stress, high salt, low temperature, and vgrG mutation, compared to the control. However, pathogen growth was unaffected by co-culture with a rice rhizobacterium Burkholderia seminalis R456. In addition, expression of 14 T6SS structural and eight vgrG genes was significantly changed under seven conditions. Among different stress conditions, high salt, and low temperature showed a higher effect on the expression of T6SS gene compared with host infection and other environmental conditions. As a first report, this study revealed an association of T6SS gene expression of the pathogen with the host infection, gene mutation, and some common environmental stresses. The results of this research can increase understanding of the biological function of T6SS in this economically-important pathogen of rice. PMID:26378528

Multi-Probe Investigation of Proteomic Structure of Pathogens

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

Malkin, A J; Plomp, M; Leighton, T J

Complete genome sequences are available for understanding biotransformation, environmental resistance and pathogenesis of microbial, cellular and pathogen systems. The present technological and scientific challenges are to unravel the relationships between the organization and function of protein complexes at cell, microbial and pathogens surfaces, to understand how these complexes evolve during the bacterial, cellular and pathogen life cycles, and how they respond to environmental changes, chemical stimulants and therapeutics. In particular, elucidating the molecular structure and architecture of human pathogen surfaces is essential to understanding mechanisms of pathogenesis, immune response, physicochemical interactions, environmental resistance and development of countermeasures against bioterrorist agents.more » The objective of this project was to investigate the architecture, proteomic structure, and function of bacterial spores through a combination of high-resolution in vitro atomic force microscopy (AFM) and AFM-based immunolabeling with threat-specific antibodies. Particular attention in this project was focused on spore forming Bacillus species including the Sterne vaccine strain of Bacillus anthracis and the spore forming near-neighbor of Clostridium botulinum, C. novyi-NT. Bacillus species, including B. anthracis, the causative agent of inhalation anthrax are laboratory models for elucidating spore structure/function. Even though the complete genome sequence is available for B. subtilis, cereus, anthracis and other species, the determination and composition of spore structure/function is not understood. Prof. B. Vogelstein and colleagues at the John Hopkins University have recently developed a breakthrough bacteriolytic therapy for cancer treatment (1). They discovered that intravenously injected Clostridium novyi-NT spores germinate exclusively within the avascular regions of tumors in mice and destroy advanced cancerous lesions. The bacteria were also found to significantly improve the efficacy of chemotherapeutic drugs and radiotherapy (2,3). Currently, there is no understanding of the structure-function relationships of Clostridium novyi-NT spores. As well as their therapeutic interest, studies of Clostridium noyii spores could provide a model for further studies of human pathogenic spore formers including Clostridium botulinum and Clostridium perfringens. This project involved a multi-institutional collaboration of our LLNL group with the groups of Prof. T.J. Leighton (Children's Hospital Oakland Research Institute) and Prof. B. Vogelstein (The Howard Hughes Medical Institute and the Ludwig Center for Cancer Genetics and Therapeutics at The John Hopkins Sidney Kimmel Comprehensive Cancer Center).« less

Modeling change in potential landscape vulnerability to forest insect and pathogen disturbances: methods for forested subwatersheds sampled in the midscale interior Columbia River basin assessment.

Treesearch

Paul F. Hessburg; Bradley G. Smith; Craig A. Miller; Scott D. Kreiter; R. Brion Salter

1999-01-01

In the interior Columbia River basin midscale ecological assessment, including portions of the Klamath and Great Basins, we mapped and characterized historical and current vegetation composition and structure of 337 randomly sampled subwatersheds (9500 ha average size) in 43 subbasins (404 000 ha average size). We compared landscape patterns, vegetation structure and...

Increased seawater temperature increases the abundance and alters the structure of natural Vibrio populations associated with the coral Pocillopora damicornis

PubMed Central

Tout, Jessica; Siboni, Nachshon; Messer, Lauren F.; Garren, Melissa; Stocker, Roman; Webster, Nicole S.; Ralph, Peter J.; Seymour, Justin R.

2015-01-01

Rising seawater temperature associated with global climate change is a significant threat to coral health and is linked to increasing coral disease and pathogen-related bleaching events. We performed heat stress experiments with the coral Pocillopora damicornis, where temperature was increased to 31°C, consistent with the 2–3°C predicted increase in summer sea surface maxima. 16S rRNA amplicon sequencing revealed a large shift in the composition of the bacterial community at 31°C, with a notable increase in Vibrio, including known coral pathogens. To investigate the dynamics of the naturally occurring Vibrio community, we performed quantitative PCR targeting (i) the whole Vibrio community and (ii) the coral pathogen Vibrio coralliilyticus. At 31°C, Vibrio abundance increased by 2–3 orders of magnitude and V. coralliilyticus abundance increased by four orders of magnitude. Using a Vibrio-specific amplicon sequencing assay, we further demonstrated that the community composition shifted dramatically as a consequence of heat stress, with significant increases in the relative abundance of known coral pathogens. Our findings provide quantitative evidence that the abundance of potential coral pathogens increases within natural communities of coral-associated microbes as a consequence of rising seawater temperature and highlight the potential negative impacts of anthropogenic climate change on coral reef ecosystems. PMID:26042096

Seasonality and pathogen transmission in pastoral cattle contact networks.

PubMed

VanderWaal, Kimberly; Gilbertson, Marie; Okanga, Sharon; Allan, Brian F; Craft, Meggan E

2017-12-01

Capturing heterogeneity in contact patterns in animal populations is essential for understanding the spread of infectious diseases. In contrast to other regions of the world in which livestock movement networks are integral to pathogen prevention and control policies, contact networks are understudied in pastoral regions of Africa due to the challenge of measuring contact among mobile herds of cattle whose movements are driven by access to resources. Furthermore, the extent to which seasonal changes in the distribution of water and resources impacts the structure of contact networks in cattle is uncertain. Contact networks may be more conducive to pathogen spread in the dry season due to congregation at limited water sources. Alternatively, less abundant forage may result in decreased pathogen transmission due to competitive avoidance among herds, as measured by reduced contact rates. Here, we use GPS technology to concurrently track 49 free-roaming cattle herds within a semi-arid region of Kenya, and use these data to characterize seasonal contact networks and model the spread of a highly infectious pathogen. This work provides the first empirical data on the local contact network structure of mobile herds based on quantifiable contact events. The contact network demonstrated high levels of interconnectivity. An increase in contacts near to water resources in the dry season resulted in networks with both higher contact rates and higher potential for pathogen spread than in the wet season. Simulated disease outbreaks were also larger in the dry season. Results support the hypothesis that limited water resources enhance connectivity and transmission within contact networks, as opposed to reducing connectivity as a result of competitive avoidance. These results cast light on the impact of seasonal heterogeneity in resource availability on predicting pathogen transmission dynamics, which has implications for other free-ranging wild and domestic populations.

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.

Where Do We Go From Here?

Treesearch

Martin L. Blaney; Scott Simon; James M. Guldin; Tom Riley; Donny Harris; Rebecca McPeake

2004-01-01

The structure and diversity of the upland oak ecosystem has changed significantly, primarily caused by fire suppression and historic forestry practices, leaving the ecosystem vulnerable to outbreaks of pathogens and insects. These conditions, coupled with periods of drought, have caused significant oak mortality throughout the Interior Highland region shifting the...

Land-Use Change Alters Host and Vector Communities and May Elevate Disease Risk.

PubMed

Guo, Fengyi; Bonebrake, Timothy C; Gibson, Luke

2018-04-24

Land-use change has transformed most of the planet. Concurrently, recent outbreaks of various emerging infectious diseases have raised great attention to the health consequences of anthropogenic environmental degradation. Here, we assessed the global impacts of habitat conversion and other land-use changes on community structures of infectious disease hosts and vectors, using a meta-analysis of 37 studies. From 331 pairwise comparisons of disease hosts/vectors in pristine (undisturbed) and disturbed areas, we found a decrease in species diversity but an increase in body size associated with land-use changes, potentially suggesting higher risk of infectious disease transmission in disturbed habitats. Neither host nor vector abundance, however, changed significantly following disturbance. When grouped by subcategories like disturbance type, taxonomic group, pathogen type and region, changes in host/vector community composition varied considerably. Fragmentation and agriculture in particular benefit host and vector communities and therefore might elevate disease risk. Our results indicate that while habitat disturbance could alter disease host/vector communities in ways that exacerbate pathogen prevalence, the relationship is highly context-dependent and influenced by multiple factors.

Enteric Pathogen-Plant Interactions: Molecular Connections Leading to Colonization and Growth and Implications for Food Safety

PubMed Central

Martínez-Vaz, Betsy M.; Fink, Ryan C.; Diez-Gonzalez, Francisco; Sadowsky, Michael J.

2014-01-01

Leafy green vegetables have been identified as a source of foodborne illnesses worldwide over the past decade. Human enteric pathogens, such as Escherichia coli O157:H7 and Salmonella, have been implicated in numerous food poisoning outbreaks associated with the consumption of fresh produce. An understanding of the mechanisms responsible for the establishment of pathogenic bacteria in or on vegetable plants is critical for understanding and ameliorating this problem as well as ensuring the safety of our food supply. While previous studies have described the growth and survival of enteric pathogens in the environment and also the risk factors associated with the contamination of vegetables, the molecular events involved in the colonization of fresh produce by enteric pathogens are just beginning to be elucidated. This review summarizes recent findings on the interactions of several bacterial pathogens with leafy green vegetables. Changes in gene expression linked to the bacterial attachment and colonization of plant structures are discussed in light of their relevance to plant-microbe interactions. We propose a mechanism for the establishment and association of enteric pathogens with plants and discuss potential strategies to address the problem of foodborne illness linked to the consumption of leafy green vegetables. PMID:24859308

[Construction and application of bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer].

PubMed

Fang, Xiang; Li, Ning-qiu; Fu, Xiao-zhe; Li, Kai-bin; Lin, Qiang; Liu, Li-hui; Shi, Cun-bin; Wu, Shu-qin

2015-07-01

As a key component of life science, bioinformatics has been widely applied in genomics, transcriptomics, and proteomics. However, the requirement of high-performance computers rather than common personal computers for constructing a bioinformatics platform significantly limited the application of bioinformatics in aquatic science. In this study, we constructed a bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer. The platform consisted of three functional modules, including genomic and transcriptomic sequencing data analysis, protein structure prediction, and molecular dynamics simulations. To validate the practicability of the platform, we performed bioinformatic analysis on aquatic pathogenic organisms. For example, genes of Flavobacterium johnsoniae M168 were identified and annotated via Blast searches, GO and InterPro annotations. Protein structural models for five small segments of grass carp reovirus HZ-08 were constructed by homology modeling. Molecular dynamics simulations were performed on out membrane protein A of Aeromonas hydrophila, and the changes of system temperature, total energy, root mean square deviation and conformation of the loops during equilibration were also observed. These results showed that the bioinformatic analysis platform for aquatic pathogen has been successfully built on the MilkyWay-2 supercomputer. This study will provide insights into the construction of bioinformatic analysis platform for other subjects.

Modify the Histone to Win the Battle: Chromatin Dynamics in Plant–Pathogen Interactions

PubMed Central

Ramirez-Prado, Juan S.; Piquerez, Sophie J. M.; Bendahmane, Abdelhafid; Hirt, Heribert; Raynaud, Cécile; Benhamed, Moussa

2018-01-01

Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant–pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses. Herein, we review the state of the art in the epigenomic aspects of plant immunity, focusing on chromatin modifications, chromatin modifiers, and their physiological consequences. In addition, we explore the exciting field of understanding how plant pathogens have adapted to manipulate the plant epigenomic regulation in order to weaken their immune system and thrive in their host, as well as how histone modifications in eukaryotic pathogens are involved in the regulation of their virulence. PMID:29616066

Functional and structural analysis of a highly-expressed Yersinia pestis small RNA following infection of cultured macrophages

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

Li, Nan; Hennelly, Scott P.; Stubben, Chris J.

Non-coding small RNAs (sRNAs) are found in practically all bacterial genomes and play important roles in regulating gene expression to impact bacterial metabolism, growth, and virulence. We performed transcriptomics analysis to identify sRNAs that are differentially expressed in Yersinia pestis that invaded the human macrophage cell line THP-1, compared to pathogens that remained extracellular in the presence of host. Using ultra high-throughput sequencing, we identified 37 novel and 143 previously known sRNAs in Y. pestis. In particular, the sRNA Ysr170 was highly expressed in intracellular Yersinia and exhibited a log2 fold change ~3.6 higher levels compared to extracellular bacteria. Wemore » found that knock-down of Ysr170 expression attenuated infection efficiency in cell culture and growth rate in response to different stressors. In addition, we applied selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) analysis to determine the secondary structure of Ysr170 and observed structural changes resulting from interactions with the aminoglycoside antibiotic gentamycin and the RNA chaperone Hfq. Interestingly, gentamicin stabilized helix 4 of Ysr170, which structurally resembles the native gentamicin 16S ribosomal binding site. Lastly, we modeled the tertiary structure of Ysr170 binding to gentamycin using RNA motif modeling. Integration of these experimental and structural methods can provide further insight into the design of small molecules that can inhibit function of sRNAs required for pathogen virulence.« less

Functional and structural analysis of a highly-expressed Yersinia pestis small RNA following infection of cultured macrophages

DOE PAGES

Li, Nan; Hennelly, Scott P.; Stubben, Chris J.; ...

2016-12-28

Non-coding small RNAs (sRNAs) are found in practically all bacterial genomes and play important roles in regulating gene expression to impact bacterial metabolism, growth, and virulence. We performed transcriptomics analysis to identify sRNAs that are differentially expressed in Yersinia pestis that invaded the human macrophage cell line THP-1, compared to pathogens that remained extracellular in the presence of host. Using ultra high-throughput sequencing, we identified 37 novel and 143 previously known sRNAs in Y. pestis. In particular, the sRNA Ysr170 was highly expressed in intracellular Yersinia and exhibited a log2 fold change ~3.6 higher levels compared to extracellular bacteria. Wemore » found that knock-down of Ysr170 expression attenuated infection efficiency in cell culture and growth rate in response to different stressors. In addition, we applied selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) analysis to determine the secondary structure of Ysr170 and observed structural changes resulting from interactions with the aminoglycoside antibiotic gentamycin and the RNA chaperone Hfq. Interestingly, gentamicin stabilized helix 4 of Ysr170, which structurally resembles the native gentamicin 16S ribosomal binding site. Lastly, we modeled the tertiary structure of Ysr170 binding to gentamycin using RNA motif modeling. Integration of these experimental and structural methods can provide further insight into the design of small molecules that can inhibit function of sRNAs required for pathogen virulence.« less

Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

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

Dheer, Rishu; Patterson, Jena; Dudash, Mark

Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low)more » or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes in microbial community structure, composition and nitrite reductase expression. • The profile of nitrogen and nitroamino acid change caused by arsenic may relect increased risk of cardiovascular pathogenesis.« less

UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.

PubMed

Chanumolu, Sree Krishna; Rout, Chittaranjan; Chauhan, Rajinder S

2012-01-01

Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate pathogen-specific drug targets identification which will increase their success and durability as drugs developed against them have less chance to develop resistances and adverse impact on environment. The server is freely available at http://117.211.115.67/UDT/main.html. The standalone application (source codes) is available at http://www.bioinformatics.org/ftp/pub/bioinfojuit/UDT.rar.

Changes associated with Ebola virus adaptation to novel species.

PubMed

Pappalardo, Morena; Reddin, Ian G; Cantoni, Diego; Rossman, Jeremy S; Michaelis, Martin; Wass, Mark N

2017-07-01

Ebola viruses are not pathogenic but can be adapted to replicate and cause disease in rodents. Here, we used a structural bioinformatics approach to analyze the mutations associated with Ebola virus adaptation to rodents to elucidate the determinants of host-specific Ebola virus pathogenicity. We identified 33 different mutations associated with Ebola virus adaptation to rodents in the proteins GP, NP, L, VP24 and VP35. Only VP24, GP and NP were consistently found mutated in rodent-adapted Ebola virus strains. Fewer than five mutations in these genes seem to be required for the adaptation of Ebola viruses to a new species. The role of mutations in GP and NP is not clear. However, three VP24 mutations located in the protein interface with karyopherin α5 may enable VP24 to inhibit karyopherins and subsequently the host interferon response. Three further VP24 mutations change hydrogen bonding or cause conformational changes. Hence, there is evidence that few mutations including crucial mutations in VP24 enable Ebola virus adaptation to new hosts. Since Reston virus, the only non-human pathogenic Ebolavirus species circulates in pigs in Asia, this raises concerns that few mutations may result in novel human pathogenic Ebolaviruses. m.n.wass@kent.ac.uk , m.michaelis@kent.ac.uk or j.s.rossman@kent.ac.uk. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The highly pathogenic H7N3 avian influenza strain from July 2012 in Mexico acquired an extended cleavage site through recombination with host 28S rRNA.

PubMed

Maurer-Stroh, Sebastian; Lee, Raphael T C; Gunalan, Vithiagaran; Eisenhaber, Frank

2013-05-01

A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein. Such motif is found in H7N3 strains from chicken farm outbreaks in 2012 in Mexico. Through phylogenetic, sequence and structural analysis, we try to shed light on the role, prevalence, likelihood of appearance and origin of the inserted cleavage motifs in these H7N3 avian influenza strains. The H7N3 avian influenza strain which caused outbreaks in chicken farms in June/July 2012 in Mexico has a new extended cleavage site which is the likely reason for its high pathogenicity in these birds. This cleavage site appears to have been naturally acquired and was not present in the closest low pathogenic precursors. Structural modeling shows that insertion of a productive cleavage site is quite flexible to accept insertions of different length and with sequences from different possible origins. Different from recent cleavage site insertions, the origin of the insert here is not from the viral genome but from host 28S ribosomal RNA (rRNA) instead. This is a novelty for a natural acquisition as a similar insertion has so far only been observed in a laboratory strain before. Given the abundance of viral and host RNA in infected cells, the acquisition of a pathogenicity-enhancing extended cleavage site through a similar route by other low-pathogenic avian strains in future does not seem unlikely. Important for surveillance of these H7N3 strains, the structural sites known to enhance mammalian airborne transmission are dominated by the characteristic avian residues and the risk of human to human transmission should currently be low but should be monitored for future changes accordingly. This highly pathogenic H7N3 avian influenza strain acquired a novel extended cleavage site which likely originated from recombination with 28S rRNA from the avian host. Notably, this new virus can infect humans but currently lacks critical host receptor adaptations that would facilitate human to human transmission.

Changing geographic ranges of ticks and tick-borne pathogens: drivers, mechanisms and consequences for pathogen diversity

PubMed Central

Ogden, Nick H.; Mechai, Samir; Margos, Gabriele

2013-01-01

The geographic ranges of ticks and tick-borne pathogens are changing due to global and local environmental (including climatic) changes. In this review we explore current knowledge of the drivers for changes in the ranges of ticks and tick-borne pathogen species and strains via effects on their basic reproduction number (R0), and the mechanisms of dispersal that allow ticks and tick-borne pathogens to invade suitable environments. Using the expanding geographic distribution of the vectors and agent of Lyme disease as an example we then investigate what could be expected of the diversity of tick-borne pathogens during the process of range expansion, and compare this with what is currently being observed. Lastly we explore how historic population and range expansions and contractions could be reflected in the phylogeography of ticks and tick-borne pathogens seen in recent years, and conclude that combined study of currently changing tick and tick-borne pathogen ranges and diversity, with phylogeographic analysis, may help us better predict future patterns of invasion and diversity. PMID:24010124

Changing geographic ranges of ticks and tick-borne pathogens: drivers, mechanisms and consequences for pathogen diversity.

PubMed

Ogden, Nick H; Mechai, Samir; Margos, Gabriele

2013-01-01

The geographic ranges of ticks and tick-borne pathogens are changing due to global and local environmental (including climatic) changes. In this review we explore current knowledge of the drivers for changes in the ranges of ticks and tick-borne pathogen species and strains via effects on their basic reproduction number (R 0), and the mechanisms of dispersal that allow ticks and tick-borne pathogens to invade suitable environments. Using the expanding geographic distribution of the vectors and agent of Lyme disease as an example we then investigate what could be expected of the diversity of tick-borne pathogens during the process of range expansion, and compare this with what is currently being observed. Lastly we explore how historic population and range expansions and contractions could be reflected in the phylogeography of ticks and tick-borne pathogens seen in recent years, and conclude that combined study of currently changing tick and tick-borne pathogen ranges and diversity, with phylogeographic analysis, may help us better predict future patterns of invasion and diversity.

Morphological changes of Ganoderma boninense mycelia after challenged by Trichoderma and Bacillus

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

Alexander, Arnnyitte; Chong, Khim-Phin, E-mail: chongkp@ums.edu.my; Dayou, Jedol

Ganoderma boninense is a fungal pathogen that causes Basal Stem Rot (BSR) disease in oil palm. This deadly disease has caused major losses in the oil palm industry and no remedy is reported to date. The more promising control on G. boninense is the use of biological control agents (BCAs). Despite many attempts in using BCAs as a control agent but evidence on the colonization of BCAs and morphological changes of the pathogen is not well documented. We have investigated the effect of antagonist activity on the combination of Trichoderma spp. and Bacillus spp. on the morphology of G. boninense.more » The antagonist activity was evaluated using agar well diffusion assay. BCAs suppressed the mycelia growth of G. boninense up to 70%. Observation under Scanning Electron Microscopy (SEM) shows these BCAs induced stripping of G. boninense hyphal structure by destroying the cellular structure. Highly disrupted, disaggerated, shrivelled and lysis of G. boninense hyphal were also observed. The antifungal activity of Trichoderma spp. and Bacillus spp. observed could be associated with the production of Cell Wall Degrading Enzymes (CWDE)« less

Morphological changes of Ganoderma boninense mycelia after challenged by Trichoderma and Bacillus

NASA Astrophysics Data System (ADS)

Alexander, Arnnyitte; Dayou, Jedol; Chong, Khim-Phin

2015-07-01

Ganoderma boninense is a fungal pathogen that causes Basal Stem Rot (BSR) disease in oil palm. This deadly disease has caused major losses in the oil palm industry and no remedy is reported to date. The more promising control on G. boninense is the use of biological control agents (BCAs). Despite many attempts in using BCAs as a control agent but evidence on the colonization of BCAs and morphological changes of the pathogen is not well documented. We have investigated the effect of antagonist activity on the combination of Trichoderma spp. and Bacillus spp. on the morphology of G. boninense. The antagonist activity was evaluated using agar well diffusion assay. BCAs suppressed the mycelia growth of G. boninense up to 70%. Observation under Scanning Electron Microscopy (SEM) shows these BCAs induced stripping of G. boninense hyphal structure by destroying the cellular structure. Highly disrupted, disaggerated, shrivelled and lysis of G. boninense hyphal were also observed. The antifungal activity of Trichoderma spp. and Bacillus spp. observed could be associated with the production of Cell Wall Degrading Enzymes (CWDE).

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%.

Challenges and priorities for modelling livestock health and pathogens in the context of climate change

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

Özkan, Şeyda

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire basedmore » exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. - Highlights: • Experts identified challenges for health and pathogen modelling under climate change. • Eighteen key challenges and associated research priorities were identified. • Increasing capacity will require improved organisation and sharing knowledge. • Better communication across the diverse topics and approaches in this field is needed.« less

Soil fungi colony growth and community dynamics

NASA Astrophysics Data System (ADS)

Falconer, Ruth E.; Kravchenko, Alexandra; Otten, Wilfred

2010-05-01

Fungi are a major player in soil functioning, they contribute to soil structure formation and shaping of plant communities through their role in nutrient cycling, pathogenesis and symbiosis. Theoretical approaches which have emerged over the years and improved considerably our understanding of above ground plant communities are still lacking below ground. A theoretical framework is needed, such that links soil physics, fungal biology and mathematical biology in order to understand fungal community dynamics and diversity in undisturbed soils. Such a framework is essential if we are to understand how environmental change or soil manipulation impacts biodiversity. Different land use and management practices significantly affect soil environmental characteristics crucial for fungal communities by contributing different quantities and qualities of biomass inputs, generating different levels of soil disturbance, influencing soil temperature and moisture regimes, and affecting structure and geometry of soil pore space. Differences in pore structures generated by long-term differences in land use and management are reflected in notable changes in soil physical and hydraulic properties, including soil porosity, hydraulic conductivity and water retention (Brye and Pirani, 2005). Changes in numbers, shapes, and distributions of soil macropores have been often observed (e.g., Pachepsky et al., 1996; Giménez et al., 1997; Udawatta et al., 2008). However, specific implications of these differences in pore structure and geometries for ability of pathogenic as well as non-pathogenic fungi to colonize soil have not yet been addressed. Recent advances in computed tomography and microscopy facilitate detailed examination of the inner pore structures of undisturbed soil samples as well as visualization of fungal mycelia. Such tools together with modelling generate a new level of understanding of the mechanisms governing fungal behaviour at microscopic scales, and for the first time allow us to examine species interactions in a 3D soil environment.

Raft membrane domains: from a liquid-ordered membrane phase to a site of pathogen attack.

PubMed

van der Goot, F G; Harder, T

2001-04-01

While the existence of cholesterol/sphingolipid (raft) membrane domains in the plasma membrane is now supported by strong experimental evidence, the structure of these domains, their size, their dynamics, and their molecular composition remain to be understood. Raft domains are thought to represent a specific physical state of lipid bilayers, the liquid-ordered phase. Recent observations suggest that in the mammalian plasma membrane small raft domains in ordered lipid phases are in a dynamic equilibrium with a less ordered membrane environment. Rafts may be enlarged and/or stabilized by protein-mediated cross-linking of raft-associated components. These changes of plasma membrane structure are perceived by the cells as signals, most likely an important element of immunoreceptor signalling. Pathogens abuse raft domains on the host cell plasma membrane as concentration devices, as signalling platforms and/or entry sites into the cell. Elucidation of these interactions requires a detailed understanding raft structure and dynamics. Copyright 2001 Academic Press.

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.

Changes in microbial community structure in the wake of Hurricanes Katrina and Rita.

PubMed

Amaral-Zettler, Linda A; Rocca, Jennifer D; Lamontagne, Michael G; Dennett, Mark R; Gast, Rebecca J

2008-12-15

Hurricanes have the potential to alter the structures of coastal ecosystems and generate pathogen-laden floodwaters thatthreaten public health. To examine the impact of hurricanes on urban systems, we compared microbial community structures in samples collected after Hurricane Katrina and before and after Hurricane Rita. We extracted environmental DNA and sequenced small-subunit rRNA (SSU rRNA) gene clone libraries to survey microbial communities in floodwater, water, and sediment samples collected from Lake Charles, Lake Pontchartrain, the 17th Street and Industrial Canals in New Orleans, and raw sewage. Correspondence analysis showed that microbial communities associated with sediments formed one cluster while communities associated with lake and Industrial Canal water formed a second. Communities associated with water from the 17th Street Canal and floodwaters collected in New Orleans showed similarity to communities in raw sewage and contained a number of sequences associated with possible pathogenic microbes. This suggests that a distinct microbial community developed in floodwaters following Hurricane Katrina and that microbial community structures as a whole might be sensitive indicators of ecosystem health and serve as "sentinels" of water quality in the environment.

Occupancy Modeling for Improved Accuracy and Understanding of Pathogen Prevalence and Dynamics

PubMed Central

Colvin, Michael E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

2015-01-01

Most pathogen detection tests are imperfect, with a sensitivity < 100%, thereby resulting in the potential for a false negative, where a pathogen is present but not detected. False negatives in a sample inflate the number of non-detections, negatively biasing estimates of pathogen prevalence. Histological examination of tissues as a diagnostic test can be advantageous as multiple pathogens can be examined and providing important information on associated pathological changes to the host. However, it is usually less sensitive than molecular or microbiological tests for specific pathogens. Our study objectives were to 1) develop a hierarchical occupancy model to examine pathogen prevalence in spring Chinook salmon Oncorhynchus tshawytscha and their distribution among host tissues 2) use the model to estimate pathogen-specific test sensitivities and infection rates, and 3) illustrate the effect of using replicate within host sampling on sample sizes required to detect a pathogen. We examined histological sections of replicate tissue samples from spring Chinook salmon O. tshawytscha collected after spawning for common pathogens seen in this population: Apophallus/echinostome metacercariae, Parvicapsula minibicornis, Nanophyetus salmincola/ metacercariae, and Renibacterium salmoninarum. A hierarchical occupancy model was developed to estimate pathogen and tissue-specific test sensitivities and unbiased estimation of host- and organ-level infection rates. Model estimated sensitivities and host- and organ-level infections rates varied among pathogens and model estimated infection rate was higher than prevalence unadjusted for test sensitivity, confirming that prevalence unadjusted for test sensitivity was negatively biased. The modeling approach provided an analytical approach for using hierarchically structured pathogen detection data from lower sensitivity diagnostic tests, such as histology, to obtain unbiased pathogen prevalence estimates with associated uncertainties. Accounting for test sensitivity using within host replicate samples also required fewer individual fish to be sampled. This approach is useful for evaluating pathogen or microbe community dynamics when test sensitivity is <100%. PMID:25738709

Occupancy modeling for improved accuracy and understanding of pathogen prevalence and dynamics

USGS Publications Warehouse

Colvin, Michael E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

2015-01-01

Most pathogen detection tests are imperfect, with a sensitivity < 100%, thereby resulting in the potential for a false negative, where a pathogen is present but not detected. False negatives in a sample inflate the number of non-detections, negatively biasing estimates of pathogen prevalence. Histological examination of tissues as a diagnostic test can be advantageous as multiple pathogens can be examined and providing important information on associated pathological changes to the host. However, it is usually less sensitive than molecular or microbiological tests for specific pathogens. Our study objectives were to 1) develop a hierarchical occupancy model to examine pathogen prevalence in spring Chinook salmonOncorhynchus tshawytscha and their distribution among host tissues 2) use the model to estimate pathogen-specific test sensitivities and infection rates, and 3) illustrate the effect of using replicate within host sampling on sample sizes required to detect a pathogen. We examined histological sections of replicate tissue samples from spring Chinook salmon O. tshawytscha collected after spawning for common pathogens seen in this population:Apophallus/echinostome metacercariae, Parvicapsula minibicornis, Nanophyetus salmincola/metacercariae, and Renibacterium salmoninarum. A hierarchical occupancy model was developed to estimate pathogen and tissue-specific test sensitivities and unbiased estimation of host- and organ-level infection rates. Model estimated sensitivities and host- and organ-level infections rates varied among pathogens and model estimated infection rate was higher than prevalence unadjusted for test sensitivity, confirming that prevalence unadjusted for test sensitivity was negatively biased. The modeling approach provided an analytical approach for using hierarchically structured pathogen detection data from lower sensitivity diagnostic tests, such as histology, to obtain unbiased pathogen prevalence estimates with associated uncertainties. Accounting for test sensitivity using within host replicate samples also required fewer individual fish to be sampled. This approach is useful for evaluating pathogen or microbe community dynamics when test sensitivity is <100%.

Global and local environmental changes as drivers of Buruli ulcer emergence.

PubMed

Combe, Marine; Velvin, Camilla Jensen; Morris, Aaron; Garchitorena, Andres; Carolan, Kevin; Sanhueza, Daniel; Roche, Benjamin; Couppié, Pierre; Guégan, Jean-François; Gozlan, Rodolphe Elie

2017-04-26

Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen's prevalence in the environment and may explain disease emergence.

Where the woodland ends: How edges affect landscape structure and physiological responses of Quercus agrifolia

NASA Astrophysics Data System (ADS)

de Chant, Timothy Paul

Forests and woodlands are integral parts of ecosystems across the globe, but they are threatened by a variety of factors, including urbanization and introduced forest pathogens. These two forces are fundamentally altering ecosystems, both by removing forest cover and reshaping landscapes. Comprehending how these two processes have changed forest ecosystems is an important step toward understanding how the affected systems will function in the future. I investigated the range of edge effects that result from disturbance brought about by forest pathogens and urbanization in two coastal oak woodlands in Marin County, California. Oak woodlands are a dynamic part of California's landscape, reacting to changes in their biotic and abiotic environments across a range of spatial and temporal scales. Sudden Oak Death, caused by the introduced forest pathogen Phytophthora ramorum, has led to widespread mortality of many tree species in California's oak woodlands. I investigated how the remaining trees respond to such rapid changes in canopy structure (Chapter 2), and my results revealed a forest canopy quick to respond to the new openings. Urbanization, another disturbance regime, operates on a longer time scale. Immediately following urban development, forest edges are strikingly linear, but both forest processes and homeowner actions likely work in concert to disrupt the straight edge (Chapter 3). Forest edges grew more sinuous within 14 years of the initial disturbance, and continued to do so for the remainder of the study, another 21 years. Individual Quercus agrifolia trees also respond to urban edges decades after disturbance (Chapter 4), and their reaction is reflected in declining stable carbon isotope values (delta13C). This change suggests trees may have increased their stomatal conductance in response to greater water availability, reduced their photosynthetic rate as a result of stress, or some combination of both. Edges have far reaching and long lasting effects on forest structure and function. Investigations of their impacts on multiple spatial and temporal scales are important in determining the range of effects they have on forest ecosystems. Studies that combine remote sensing, geographic information systems, and field studies may help us understand the ecological consequences of forest edges.

Biotic stress induced demolition of thylakoid structure and loss in photoelectron transport of chloroplasts in papaya leaves.

PubMed

Nanda, Rashmi Madhumita; Biswal, Basanti

2008-04-01

Papaya mosaic virus (PMV) causes severe mosaic symptoms in the papaya (Carica papaya L.) leaves. The PMV-induced alterations in photosystem II (PS II) structure and photochemical functions were probed. An increase in chlorophyll a (Chl a) fluorescence polarization suggests pathogen-induced transformation of thylakoid membrane to a gel phase. This transformation in physical state of thylakoid membrane may result in alteration in topology of pigments on pigment-binding proteins as reflected in pathogen-induced loss in the efficiency of energy transfer from carotenoids to chlorophylls. The fast Chl a fluorescence induction kinetics of healthy and PMV-infected plants by F(O)-F(J)-F(I)-F(P) transients revealed pathogen-induced perturbation on PS II acceptor side electron transfer equilibrium between Q(A) and Q(B) and in the pool size of electron transport acceptors. Pathogen-induced loss in photosynthetic pigments, changes in thylakoid structure and decrease in the ratio of F(V)/F(M) (photochemical potential of PS II) further correlate with the loss in photoelectron transport of PS II as probed by 2,6-dichlorophenol indophenol (DCPIP)-Hill reaction. Restoration of the loss by 1,5-diphenyl carbazide (DPC), an exogenous electron donor, that donates electron directly to reaction centre II bypassing the oxygen evolving system (OES), leads towards the conclusion that OES is one of the major targets of biotic stress. Further, the data suggest that chlorophyll fluorescence could be used as a non-invasive handy tool to assess the loss in photosynthetic efficiency and symptom severity in infected green tissues vis-a-vis the healthy ones.

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

Investigating the Responses of Cronobacter sakazakii to Garlic-Drived Organosulfur Compounds: a Systematic Study of Pathogenic-Bacterium Injury by Use of High-Throughput Whole-Transcriptome Sequencing and Confocal Micro-Raman Spectroscopy

PubMed Central

Feng, Shaolong; Eucker, Tyson P.; Holly, Mayumi K.; Konkel, Michael E.

2014-01-01

We present the results of a study using high-throughput whole-transcriptome sequencing (RNA-seq) and vibrational spectroscopy to characterize and fingerprint pathogenic-bacterium injury under conditions of unfavorable stress. Two garlic-derived organosulfur compounds were found to be highly effective antimicrobial compounds against Cronobacter sakazakii, a leading pathogen associated with invasive infection of infants and causing meningitis, necrotizing entercolitis, and bacteremia. RNA-seq shows changes in gene expression patterns and transcriptomic response, while confocal micro-Raman spectroscopy characterizes macromolecular changes in the bacterial cell resulting from this chemical stress. RNA-seq analyses showed that the bacterial response to ajoene differed from the response to diallyl sulfide. Specifically, ajoene caused downregulation of motility-related genes, while diallyl sulfide treatment caused an increased expression of cell wall synthesis genes. Confocal micro-Raman spectroscopy revealed that the two compounds appear to have the same phase I antimicrobial mechanism of binding to thiol-containing proteins/enzymes in bacterial cells generating a disulfide stretching band but different phase II antimicrobial mechanisms, showing alterations in the secondary structures of proteins in two different ways. Diallyl sulfide primarily altered the α-helix and β-sheet, as reflected in changes in amide I, while ajoene altered the structures containing phenylalanine and tyrosine. Bayesian probability analysis validated the ability of principal component analysis to differentiate treated and control C. sakazakii cells. Scanning electron microscopy confirmed cell injury, showing significant morphological variations in cells following treatments by these two compounds. Findings from this study aid in the development of effective intervention strategies to reduce the risk of C. sakazakii contamination in the food production environment and on food contact surfaces, reducing the risks to susceptible consumers. PMID:24271174

Early animal farming and zoonotic disease dynamics: modelling brucellosis transmission in Neolithic goat populations.

PubMed

Fournié, Guillaume; Pfeiffer, Dirk U; Bendrey, Robin

2017-02-01

Zoonotic pathogens are frequently hypothesized as emerging with the origins of farming, but evidence of this is elusive in the archaeological records. To explore the potential impact of animal domestication on zoonotic disease dynamics and human infection risk, we developed a model simulating the transmission of Brucella melitensis within early domestic goat populations. The model was informed by archaeological data describing goat populations in Neolithic settlements in the Fertile Crescent, and used to assess the potential of these populations to sustain the circulation of Brucella . Results show that the pathogen could have been sustained even at low levels of transmission within these domestic goat populations. This resulted from the creation of dense populations and major changes in demographic characteristics. The selective harvesting of young male goats, likely aimed at improving the efficiency of food production, modified the age and sex structure of these populations, increasing the transmission potential of the pathogen within these populations. Probable interactions between Neolithic settlements would have further promoted pathogen maintenance. By fostering conditions suitable for allowing domestic goats to become reservoirs of Brucella melitensis , the early stages of agricultural development were likely to promote the exposure of humans to this pathogen.

Early animal farming and zoonotic disease dynamics: modelling brucellosis transmission in Neolithic goat populations

PubMed Central

Pfeiffer, Dirk U.; Bendrey, Robin

2017-01-01

Zoonotic pathogens are frequently hypothesized as emerging with the origins of farming, but evidence of this is elusive in the archaeological records. To explore the potential impact of animal domestication on zoonotic disease dynamics and human infection risk, we developed a model simulating the transmission of Brucella melitensis within early domestic goat populations. The model was informed by archaeological data describing goat populations in Neolithic settlements in the Fertile Crescent, and used to assess the potential of these populations to sustain the circulation of Brucella. Results show that the pathogen could have been sustained even at low levels of transmission within these domestic goat populations. This resulted from the creation of dense populations and major changes in demographic characteristics. The selective harvesting of young male goats, likely aimed at improving the efficiency of food production, modified the age and sex structure of these populations, increasing the transmission potential of the pathogen within these populations. Probable interactions between Neolithic settlements would have further promoted pathogen maintenance. By fostering conditions suitable for allowing domestic goats to become reservoirs of Brucella melitensis, the early stages of agricultural development were likely to promote the exposure of humans to this pathogen. PMID:28386446

Method for detecting pathogens attached to specific antibodies

DOEpatents

Miles, Robin R.; Venkateswaran, Kodumudi S.; Fuller, Christopher K.

2005-01-25

The use of impedance measurements to detect the presence of pathogens attached to antibody-coated beads. In a fluidic device antibodies are immobilized on a surface of a patterned interdigitated electrode. Pathogens in a sample fluid streaming past the electrode attach to the immobilized antibodies, which produces a change in impedance between two adjacent electrodes, which impedance change is measured and used to detect the presence of a pathogen. To amplify the signal, beads coated with antibodies are introduced and the beads would stick to the pathogen causing a greater change in impedance between the two adjacent electrodes.

Impedance measurements for detecting pathogens attached to antibodies

DOEpatents

Miles, Robin R.; Venkateswaran, Kodumudi S.; Fuller, Christopher K.

2004-12-28

The use of impedance measurements to detect the presence of pathogens attached to antibody-coated beads. In a fluidic device antibodies are immobilized on a surface of a patterned interdigitated electrode. Pathogens in a sample fluid streaming past the electrode attach to the immobilized antibodies, which produces a change in impedance between two adjacent electrodes, which impedance change is measured and used to detect the presence of a pathogen. To amplify the signal, beads coated with antibodies are introduced and the beads would stick to the pathogen causing a greater change in impedance between the two adjacent electrodes.

The Interface between Fungal Biofilms and Innate Immunity.

PubMed

Kernien, John F; Snarr, Brendan D; Sheppard, Donald C; Nett, Jeniel E

2017-01-01

Fungal biofilms are communities of adherent cells surrounded by an extracellular matrix. These biofilms are commonly found during infection caused by a variety of fungal pathogens. Clinically, biofilm infections can be extremely difficult to eradicate due to their resistance to antifungals and host defenses. Biofilm formation can protect fungal pathogens from many aspects of the innate immune system, including killing by neutrophils and monocytes. Altered immune recognition during this phase of growth is also evident by changes in the cytokine profiles of monocytes and macrophages exposed to biofilm. In this manuscript, we review the host response to fungal biofilms, focusing on how these structures are recognized by the innate immune system. Biofilms formed by Candida, Aspergillus , and Cryptococcus have received the most attention and are highlighted. We describe common themes involved in the resilience of fungal biofilms to host immunity and give examples of biofilm defenses that are pathogen-specific.

Adaptation of mammalian host-pathogen interactions in a changing arctic environment

PubMed Central

2011-01-01

Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic. PMID:21392401

Adaptation of mammalian host-pathogen interactions in a changing arctic environment.

PubMed

Hueffer, Karsten; O'Hara, Todd M; Follmann, Erich H

2011-03-11

Many arctic mammals are adapted to live year-round in extreme environments with low winter temperatures and great seasonal variations in key variables (e.g. sunlight, food, temperature, moisture). The interaction between hosts and pathogens in high northern latitudes is not very well understood with respect to intra-annual cycles (seasons). The annual cycles of interacting pathogen and host biology is regulated in part by highly synchronized temperature and photoperiod changes during seasonal transitions (e.g., freezeup and breakup). With a warming climate, only one of these key biological cues will undergo drastic changes, while the other will remain fixed. This uncoupling can theoretically have drastic consequences on host-pathogen interactions. These poorly understood cues together with a changing climate by itself will challenge host populations that are adapted to pathogens under the historic and current climate regime. We will review adaptations of both host and pathogens to the extreme conditions at high latitudes and explore some potential consequences of rapid changes in the Arctic.

Historical and current forest and range landscapes in the interior Columbia River basin and portions of the Klamath and Great Basins. Part 1: Linking vegetation patterns and landscape vulnerability to potential insect and pathogen disturbances.

Treesearch

Paul F. Hessburg; Bradley G. Smith; Scott D. Kreiter; Craig A. Miller; R. Brion Salter; Cecilia H. McNicoll; Wendel J. Hann

1999-01-01

Management activities of the 20th century, especially fire exclusion, timber harvest, and domestic livestock grazing, have significantly modified vegetation spatial patterns of forests and ranges in the interior Columbia basin. Compositional patterns as well as patterns of living and dead structure have changed. Dramatic change in vital ecosystem processes such as fire...

Modeling the effect of 3 missense AGXT mutations on dimerization of the AGT enzyme in primary hyperoxaluria type 1.

PubMed

Robbiano, Angela; Frecer, Vladimir; Miertus, Jan; Zadro, Cristina; Ulivi, Sheila; Bevilacqua, Elena; Mandrile, Giorgia; De Marchi, Mario; Miertus, Stanislav; Amoroso, Antonio

2010-01-01

Mutations of the AGXT gene encoding the alanine:glyoxylate aminotransferase liver enzyme (AGT) cause primary hyperoxaluria type 1 (PH1). Here we report a molecular modeling study of selected missense AGXT mutations: the common Gly170Arg and the recently described Gly47Arg and Ser81Leu variants, predicted to be pathogenic using standard criteria. Taking advantage of the refined 3D structure of AGT, we computed the dimerization energy of the wild-type and mutated proteins. Molecular modeling predicted that Gly47Arg affects dimerization with a similar effect to that shown previously for Gly170Arg through classical biochemical approaches. In contrast, no effect on dimerization was predicted for Ser81Leu. Therefore, this probably demonstrates pathogenic properties via a different mechanism, similar to that described for the adjacent Gly82Glu mutation that affects pyridoxine binding. This study shows that the molecular modeling approach can contribute to evaluating the pathogenicity of some missense variants that affect dimerization. However, in silico studies--aimed to assess the relationship between structural change and biological effects--require the integrated use of more than 1 tool.

Can mutation-mediated effects occurring early in development cause long-term seizure susceptibility in genetic generalized epilepsies?

PubMed

Reid, Christopher Alan; Rollo, Ben; Petrou, Steven; Berkovic, Samuel F

2018-05-01

Epilepsy has a strong genetic component, with an ever-increasing number of disease-causing genes being discovered. Most epilepsy-causing mutations are germ line and thus present from conception. These mutations are therefore well positioned to have a deleterious impact during early development. Here we review studies that investigate the role of genetic lesions within the early developmental window, specifically focusing on genetic generalized epilepsy (GGE). Literature on the potential pathogenic role of sub-mesoscopic structural changes in GGE is also reviewed. Evidence from rodent models of genetic epilepsy support the idea that functional and structural changes can occur in early development, leading to altered seizure susceptibility into adulthood. Both animal and human studies suggest that sub-mesoscopic structural changes occur in GGE. The existence of sub-mesoscopic structural changes prior to seizure onset may act as biomarkers of excitability in genetic epilepsies. We also propose that presymptomatic treatment may be essential for limiting the long-term consequences of disease-causing mutations in genetic epilepsies. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

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.

Sudden oak death-caused changes to surface fuel loading and potential fire behavior in Douglas-fir-tanoak forests

Treesearch

Y.S. Valachovic; C.A. Lee; H. Scanlon; J.M. Varner; R. Glebocki; B.D. Graham; D.M. Rizzo

2011-01-01

We compared stand structure and fuel loading in northwestern California forests invaded by Phytophthora ramorum, the cause of sudden oak death, to assess whether the continued presence of this pathogen alters surface fuel loading and potential fire behavior in ways that may encumber future firefighting response. To attempt to account for these...

The importance and conservation of ectomycorrizal fungal diversity in forest ecosystems: lessons from Europe and the Pacific Northwest.

Treesearch

Michael P. Amaranthus

1998-01-01

Ectomycorrhizal fungi (EMF) consist of about 5,000 species and profoundly affect forest ecosystems by mediating nutrient and water uptake, protecting roots from pathogens and environmental extremes, and maintaining soil structure and forest food webs. Diversity of EMF likely aids forest ecosystem resilience in the face of changing environmental factors such as...

Challenges and priorities for modelling livestock health and pathogens in the context of climate change.

PubMed

Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J; Blanco-Penedo, Isabel; de Haas, Yvette; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J; Garnsworthy, Phil C; Gengler, Nicolas; Hammami, Hedi; Kyriazakis, Ilias; Leclère, David; Lessire, Françoise; Macleod, Michael; Robinson, Timothy P; Ruete, Alejandro; Sandars, Daniel L; Shrestha, Shailesh; Stott, Alistair W; Twardy, Stanislaw; Vanrobays, Marie-Laure; Ahmadi, Bouda Vosough; Weindl, Isabelle; Wheelhouse, Nick; Williams, Adrian G; Williams, Hefin W; Wilson, Anthony J; Østergaard, Søren; Kipling, Richard P

2016-11-01

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. Copyright © 2016 Elsevier Inc. All rights reserved.

The ecology of emerging infectious diseases in migratory birds: an assessment of the role of climate change and priorities for future research.

PubMed

Fuller, Trevon; Bensch, Staffan; Müller, Inge; Novembre, John; Pérez-Tris, Javier; Ricklefs, Robert E; Smith, Thomas B; Waldenström, Jonas

2012-03-01

Pathogens that are maintained by wild birds occasionally jump to human hosts, causing considerable loss of life and disruption to global commerce. Preliminary evidence suggests that climate change and human movements and commerce may have played a role in recent range expansions of avian pathogens. Since the magnitude of climate change in the coming decades is predicted to exceed climatic changes in the recent past, there is an urgent need to determine the extent to which climate change may drive the spread of disease by avian migrants. In this review, we recommend actions intended to mitigate the impact of emergent pathogens of migratory birds on biodiversity and public health. Increased surveillance that builds upon existing bird banding networks is required to conclusively establish a link between climate and avian pathogens and to prevent pathogens with migratory bird reservoirs from spilling over to humans.

Looking for Broken TAD Boundaries and Changes on DNA Interactions: Clinical Guide to 3D Chromatin Change Analysis in Complex Chromosomal Rearrangements and Chromothripsis.

PubMed

Yauy, Kevin; Gatinois, Vincent; Guignard, Thomas; Sati, Satish; Puechberty, Jacques; Gaillard, Jean Baptiste; Schneider, Anouck; Pellestor, Franck

2018-01-01

Apparition of next-generation sequencing (NGS) was a breakthrough on knowledge of genome structure. Bioinformatic tools are a key point to analyze this huge amount of data from NGS and characterize the three-dimensional organization of chromosomes. This chapter describes usage of different browsers to explore publicly available online data and to search for possible 3D chromatin changes involved during complex chromosomal rearrangements as chromothripsis. Their pathogenic impact on clinical phenotype and gene misexpression can also be evaluated with annotated databases.

O Antigen Modulates Insect Vector Acquisition of the Bacterial Plant Pathogen Xylella fastidiosa

PubMed Central

Rapicavoli, Jeannette N.; Kinsinger, Nichola; Perring, Thomas M.; Backus, Elaine A.; Shugart, Holly J.; Walker, Sharon

2015-01-01

Hemipteran insect vectors transmit the majority of plant pathogens. Acquisition of pathogenic bacteria by these piercing/sucking insects requires intimate associations between the bacterial cells and insect surfaces. Lipopolysaccharide (LPS) is the predominant macromolecule displayed on the cell surface of Gram-negative bacteria and thus mediates bacterial interactions with the environment and potential hosts. We hypothesized that bacterial cell surface properties mediated by LPS would be important in modulating vector-pathogen interactions required for acquisition of the bacterial plant pathogen Xylella fastidiosa, the causative agent of Pierce's disease of grapevines. Utilizing a mutant that produces truncated O antigen (the terminal portion of the LPS molecule), we present results that link this LPS structural alteration to a significant decrease in the attachment of X. fastidiosa to blue-green sharpshooter foreguts. Scanning electron microscopy confirmed that this defect in initial attachment compromised subsequent biofilm formation within vector foreguts, thus impairing pathogen acquisition. We also establish a relationship between O antigen truncation and significant changes in the physiochemical properties of the cell, which in turn affect the dynamics of X. fastidiosa adhesion to the vector foregut. Lastly, we couple measurements of the physiochemical properties of the cell with hydrodynamic fluid shear rates to produce a Comsol model that predicts primary areas of bacterial colonization within blue-green sharpshooter foreguts, and we present experimental data that support the model. These results demonstrate that, in addition to reported protein adhesin-ligand interactions, O antigen is crucial for vector-pathogen interactions, specifically in the acquisition of this destructive agricultural pathogen. PMID:26386068

O antigen modulates insect vector acquisition of the bacterial plant pathogen Xylella fastidiosa.

PubMed

Rapicavoli, Jeannette N; Kinsinger, Nichola; Perring, Thomas M; Backus, Elaine A; Shugart, Holly J; Walker, Sharon; Roper, M Caroline

2015-12-01

Hemipteran insect vectors transmit the majority of plant pathogens. Acquisition of pathogenic bacteria by these piercing/sucking insects requires intimate associations between the bacterial cells and insect surfaces. Lipopolysaccharide (LPS) is the predominant macromolecule displayed on the cell surface of Gram-negative bacteria and thus mediates bacterial interactions with the environment and potential hosts. We hypothesized that bacterial cell surface properties mediated by LPS would be important in modulating vector-pathogen interactions required for acquisition of the bacterial plant pathogen Xylella fastidiosa, the causative agent of Pierce's disease of grapevines. Utilizing a mutant that produces truncated O antigen (the terminal portion of the LPS molecule), we present results that link this LPS structural alteration to a significant decrease in the attachment of X. fastidiosa to blue-green sharpshooter foreguts. Scanning electron microscopy confirmed that this defect in initial attachment compromised subsequent biofilm formation within vector foreguts, thus impairing pathogen acquisition. We also establish a relationship between O antigen truncation and significant changes in the physiochemical properties of the cell, which in turn affect the dynamics of X. fastidiosa adhesion to the vector foregut. Lastly, we couple measurements of the physiochemical properties of the cell with hydrodynamic fluid shear rates to produce a Comsol model that predicts primary areas of bacterial colonization within blue-green sharpshooter foreguts, and we present experimental data that support the model. These results demonstrate that, in addition to reported protein adhesin-ligand interactions, O antigen is crucial for vector-pathogen interactions, specifically in the acquisition of this destructive agricultural pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Revealing the chemical changes of tea cell wall induced by anthracnose with confocal Raman microscopy].

PubMed

Li, Xiao-li; Luo, Liu-bin; Hu, Xiao-qian; Lou, Bing-gan; He, Yong

2014-06-01

Healthy tea and tea infected by anthracnose were first studied by confocal Raman microscopy to illustrate chemical changes of cell wall in the present paper. Firstly, Raman spectra of both healthy and infected sample tissues were collected with spatial resolution at micron-level, and ultrastructure of healthy and infected tea cells was got from scanning electron microscope. These results showed that there were significant changes in Raman shift and Raman intensity between healthy and infected cell walls, indicating that great differences occurred in chemical compositions of cell walls between healthy and infected samples. In details, intensities at many Raman bands which were closely associated with cellulose, pectin, esters were reduced after infection, revealing that the content of chemical compounds such as cellulose, pectin, esters was decreased after infection. Subsequently, chemical imaging of both healthy and infected tea cell walls were realized based on Raman fingerprint spectra of cellulose and microscopic spatial structure. It was found that not only the content of cellulose was reduced greatly after infection, but also the ordered structure of cellulose was destroyed by anthracnose infection. Thus, confocal Raman microscopy was shown to be a powerful tool to detect the chemical changes in cell wall of tea caused by anthracnose without any chemical treatment or staining. This research firstly applied confocal Raman microscopy in phytopathology for the study of interactive relationship between host and pathogen, and it will also open a new way for intensive study of host-pathogen at cellular level.

Plant Defense Inhibitors Affect the Structures of Midgut Cells in Drosophila melanogaster and Callosobruchus maculatus

PubMed Central

Li-Byarlay, Hongmei; Pittendrigh, Barry R.; Murdock, Larry L.

2016-01-01

Plants produce proteins such as protease inhibitors and lectins as defenses against herbivorous insects and pathogens. However, no systematic studies have explored the structural responses in the midguts of insects when challenged with plant defensive proteins and lectins across different species. In this study, we fed two kinds of protease inhibitors and lectins to the fruit fly Drosophila melanogaster and alpha-amylase inhibitors and lectins to the cowpea bruchid Callosobruchus maculatus. We assessed the changes in midgut cell structures by comparing them with such structures in insects receiving normal diets or subjected to food deprivation. Using light and transmission electron microscopy in both species, we observed structural changes in the midgut peritrophic matrix as well as shortened microvilli on the surfaces of midgut epithelial cells in D. melanogaster. Dietary inhibitors and lectins caused similar lesions in the epithelial cells but not much change in the peritrophic matrix in both species. We also noted structural damages in the Drosophila midgut after six hours of starvation and changes were still present after 12 hours. Our study provided the first evidence of key structural changes of midguts using a comparative approach between a dipteran and a coleopteran. Our particular observation and discussion on plant–insect interaction and dietary stress are relevant for future mode of action studies of plant defensive protein in insect physiology. PMID:27594789

Plant Defense Inhibitors Affect the Structures of Midgut Cells in Drosophila melanogaster and Callosobruchus maculatus.

PubMed

Li-Byarlay, Hongmei; Pittendrigh, Barry R; Murdock, Larry L

2016-01-01

Plants produce proteins such as protease inhibitors and lectins as defenses against herbivorous insects and pathogens. However, no systematic studies have explored the structural responses in the midguts of insects when challenged with plant defensive proteins and lectins across different species. In this study, we fed two kinds of protease inhibitors and lectins to the fruit fly Drosophila melanogaster and alpha-amylase inhibitors and lectins to the cowpea bruchid Callosobruchus maculatus. We assessed the changes in midgut cell structures by comparing them with such structures in insects receiving normal diets or subjected to food deprivation. Using light and transmission electron microscopy in both species, we observed structural changes in the midgut peritrophic matrix as well as shortened microvilli on the surfaces of midgut epithelial cells in D. melanogaster. Dietary inhibitors and lectins caused similar lesions in the epithelial cells but not much change in the peritrophic matrix in both species. We also noted structural damages in the Drosophila midgut after six hours of starvation and changes were still present after 12 hours. Our study provided the first evidence of key structural changes of midguts using a comparative approach between a dipteran and a coleopteran. Our particular observation and discussion on plant-insect interaction and dietary stress are relevant for future mode of action studies of plant defensive protein in insect physiology.

Incorporating climate change into pest risk models for forest pathogens: a role for cold stress in an era of global warming?

Treesearch

Robert C. Venette

2013-01-01

Climate change may alter the distribution and activity of native and alien pathogens that infect trees and, in severe cases, cause tree death. In this study, potential future changes in climate suitability are investigated for three forest pathogens that occur in western North America: the native Arceuthobium tsugense subsp tsugense...

Endoplasmic reticulum-dependent redox reactions control endoplasmic reticulum-associated degradation and pathogen entry.

PubMed

Walczak, Christopher P; Bernardi, Kaleena M; Tsai, Billy

2012-04-15

Protein misfolding within the endoplasmic reticulum (ER) is managed by an ER quality control system that retro-translocates aberrant proteins into the cytosol for proteasomal destruction. This process, known as ER-associated degradation, utilizes the action of ER redox enzymes to accommodate the disulfide-bonded nature of misfolded proteins. Strikingly, various pathogenic viruses and toxins co-opt these redox components to reach the cytosol during entry. These redox factors thus regulate critical cellular homeostasis and host-pathogen interactions. Recent studies identify specific members of the protein disulfide isomerase (PDI) family, which use their chaperone and catalytic activities, in engaging both misfolded ER proteins and pathogens. The precise molecular mechanism by which a dedicated PDI family member disrupts the disulfide bonds in the misfolded ER proteins and pathogens, as well as how they act to unfold these substrates to promote their ER-to-cytosol membrane transport, remain poorly characterized. How PDI family members distinguish folded versus misfolded ER substrates remains enigmatic. What physical characteristics surrounding a substrate's disulfide bond instruct PDI that it is mispaired or native? For the pathogens, as their disulfide bonds normally serve a critical role in providing physical support, what conformational changes experienced in the host enable their disulfide bonds to be disrupted? A combination of more rigorous biochemical and high-resolution structural studies should begin to address these questions.

Crystal Structures and Small-angle X-ray Scattering Analysis of UDP-galactopyranose Mutase from the Pathogenic Fungus Aspergillus fumigatus

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

Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle

2015-10-15

UDP-galactopyranose mutase (UGM) is a flavoenzyme that catalyzes the conversion of UDP-galactopyranose to UDP-galactofuranose, which is a central reaction in galactofuranose biosynthesis. Galactofuranose has never been found in humans but is an essential building block of the cell wall and extracellular matrix of many bacteria, fungi, and protozoa. The importance of UGM for the viability of many pathogens and its absence in humans make UGM a potential drug target. Here we report the first crystal structures and small-angle x-ray scattering data for UGM from the fungus Aspergillus fumigatus, the causative agent of aspergillosis. The structures reveal that Aspergillus UGM hasmore » several extra secondary and tertiary structural elements that are not found in bacterial UGMs yet are important for substrate recognition and oligomerization. Small-angle x-ray scattering data show that Aspergillus UGM forms a tetramer in solution, which is unprecedented for UGMs. The binding of UDP or the substrate induces profound conformational changes in the enzyme. Two loops on opposite sides of the active site move toward each other by over 10 {angstrom} to cover the substrate and create a closed active site. The degree of substrate-induced conformational change exceeds that of bacterial UGMs and is a direct consequence of the unique quaternary structure of Aspergillus UGM. Galactopyranose binds at the re face of the FAD isoalloxazine with the anomeric carbon atom poised for nucleophilic attack by the FAD N5 atom. The structural data provide new insight into substrate recognition and the catalytic mechanism and thus will aid inhibitor design.« less

3-D imaging of temporal and spatial development of Puccinia striiformis haustoria in wheat.

PubMed

Sørensen, Chris K; Justesen, Annemarie F; Hovmøller, Mogens S

2012-01-01

Differentiation of haustoria on primary infection hyphae of the fungal pathogen Puccinia striiformis was studied in wheat seedlings with two-photon microscopy in combination with a classical staining technique. Our results showed a significant increase in the average haustorium size 22, 44, 68, 92 and 116 h after inoculation (hai). After 116 hai no significant change was observed until 336 hai. Haustorium morphology also changed significantly during the time of infection. Initially small spherical haustoria were seen, but as they grew the haustoria gradually became apically branched. At 22 hai all observed haustoria were spherical, but at 44 hai most haustoria had an irregular structure, and at 92 hai all observed haustoria appeared branched. Along with the changes of the haustorial body the haustorial neck changed from narrow and slender to having an expanded appearance with a rough and invaginated structure. The structural changes were similar in two susceptible wheat varieties, 514W and Cartago, although the mean haustorium size was larger in 514W than in Cartago at all intervals.

From diagnostics to metagenomics: Applications of DNA-based tools in forest pathology

Treesearch

Amy L. Ross-Davis; Mee-Sook Kim; Jane E. Stewart; John W. Hanna; John D. Shaw; Ned B. Klopfenstein

2013-01-01

Advances in molecular technology provide an accessible set of tools to 1) help forest pathologists detect, identify, and monitor forest pathogens, 2) examine the evolutionary relationships and global distributions of forest pathogens and their hosts, 3) assess the diversity and structure of host and pathogen populations, and 4) evaluate the structure and function of...

Changes in microbial community structure in the wake of Hurricanes Katrina and Rita

PubMed Central

Amaral-Zettler, Linda A.; Rocca, Jennifer D.; LaMontagne, Michael G.; Dennett, Mark R.; Gast, Rebecca J.

2009-01-01

Hurricanes have the potential to alter the structures of coastal ecosystems and generate pathogen-laden floodwaters that threaten public health. To examine the impact of hurricanes on urban systems, we compared microbial community structures in samples collected after Hurricane Katrina and before and after Hurricane Rita. We extracted environmental DNA and sequenced small-subunit ribosomal RNA (SSU rRNA) gene clone libraries to survey microbial communities in floodwater, water and sediment samples collected from Lake Charles, Lake Pontchartrain, the 17th Street and Industrial Canals in New Orleans and raw sewage. Correspondence Analysis showed that microbial communities associated with sediments formed one cluster while communities associated with lake and Industrial Canal water formed a second. Communities associated with water from the 17th Street Canal and floodwaters collected in New Orleans showed similarity to communities in raw sewage and contained a number of sequences associated with possible pathogenic microbes. This suggests that a distinct microbial community developed in floodwaters following Hurricane Katrina and that microbial community structures as a whole might be sensitive indicators of ecosystem health and serve as “sentinels” of water quality in the environment. PMID:19174873

De novo Transcriptome Analysis of Rhizoctonia solani AG1 IA Strain Early Invasion in Zoysia japonica Root.

PubMed

Zhu, Chen; Ai, Lin; Wang, Li; Yin, Pingping; Liu, Chenglan; Li, Shanshan; Zeng, Huiming

2016-01-01

Zoysia japonica brown spot was caused by necrotrophic fungus Rhizoctonia solani invasion, which led to severe financial loss in city lawn and golf ground maintenance. However, little was known about the molecular mechanism of R. solani pathogenicity in Z. japonica. In this study we examined early stage interaction between R. solani AG1 IA strain and Z. japonica cultivar "Zenith" root by cell ultra-structure analysis, pathogenesis-related proteins assay and transcriptome analysis to explore molecular clues for AG1 IA strain pathogenicity in Z. japonica. No obvious cell structure damage was found in infected roots and most pathogenesis-related protein activities showedg a downward trend especially in 36 h post inoculation, which exhibits AG1 IA strain stealthy invasion characteristic. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database classification, most DEGs in infected "Zenith" roots dynamically changed especially in three aspects, signal transduction, gene translation, and protein synthesis. Total 3422 unigenes of "Zenith" root were predicted into 14 kinds of resistance (R) gene class. Potential fungal resistance related unigenes of "Zenith" root were involved in ligin biosynthesis, phytoalexin synthesis, oxidative burst, wax biosynthesis, while two down-regulated unigenes encoding leucine-rich repeat receptor protein kinase and subtilisin-like protease might be important for host-derived signal perception to AG1 IA strain invasion. According to Pathogen Host Interaction (PHI) database annotation, 1508 unigenes of AG1 IA strain were predicted and classified into 37 known pathogen species, in addition, unigenes encoding virulence, signaling, host stress tolerance, and potential effector were also predicted. This research uncovered transcriptional profiling during the early phase interaction between R. solani AG1 IA strain and Z. japonica, and will greatly help identify key pathogenicity of AG1 IA strain.

Immune subversion by chromatin manipulation: a 'new face' of host-bacterial pathogen interaction.

PubMed

Arbibe, Laurence

2008-08-01

Bacterial pathogens have evolved various strategies to avoid immune surveillance, depending of their in vivo'lifestyle'. The identification of few bacterial effectors capable to enter the nucleus and modifying chromatin structure in host raises the fascinating questions of how pathogens modulate chromatin structure and why. Chromatin is a dynamic structure that maintains the stability and accessibility of the host DNA genome to the transcription machinery. This review describes the various strategies used by pathogens to interface with host chromatin. In some cases, chromatin injury can be a strategy to take control of major cellular functions, such as the cell cycle. In other cases, manipulation of chromatin structure at specific genomic locations by modulating epigenetic information provides a way for the pathogen to impose its own transcriptional signature onto host cells. This emerging field should strongly influence our understanding of chromatin regulation at interphase nucleus and may provide invaluable openings to the control of immune gene expression in inflammatory and infectious diseases.

Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens.

PubMed

Liu, Yi-Yun; Chandler, Courtney E; Leung, Lisa M; McElheny, Christi L; Mettus, Roberta T; Shanks, Robert M Q; Liu, Jian-Hua; Goodlett, David R; Ernst, Robert K; Doi, Yohei

2017-06-01

mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE ( Enterococcus faecium , Staphylococcus aureus , K. pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli , K. pneumoniae , A. baumannii , and P. aeruginosa Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli , K. pneumoniae , and A. baumannii but only moderately reduced susceptibility in P. aeruginosa Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmid-mediated phosphoethanolamine transferases in general. Copyright © 2017 American Society for Microbiology.

Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens

PubMed Central

Liu, Yi-Yun; Chandler, Courtney E.; Leung, Lisa M.; McElheny, Christi L.; Mettus, Roberta T.; Liu, Jian-Hua; Goodlett, David R.

2017-01-01

ABSTRACT mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmid-mediated phosphoethanolamine transferases in general. PMID:28373195

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

PubMed

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

2008-01-14

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

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.

Resin duct size and density as ecophysiological traits in fire scars of Pseudotsuga menziesii and Larix occidentalis

Treesearch

Estelle Arbellay; Markus Stoffel; Elaine K. Sutherland; Kevin T. Smith; Donald A. Falk

2014-01-01

Resin ducts (RDs) are features present in most conifer species as defence structures against pests and pathogens; however, little is known about RD expression in trees following fire injury. This study investigates changes in RD size and density in fire scars of Douglas fir (Pseudotsuga menziesii) and western larch (Larix occidentalis) as a means to evaluate the...

Gene expression profiling during asexual development of the late blight pathogen Phytophthora infestans reveals a highly dynamic transcriptome.

PubMed

Judelson, Howard S; Ah-Fong, Audrey M V; Aux, George; Avrova, Anna O; Bruce, Catherine; Cakir, Cahid; da Cunha, Luis; Grenville-Briggs, Laura; Latijnhouwers, Maita; Ligterink, Wilco; Meijer, Harold J G; Roberts, Samuel; Thurber, Carrie S; Whisson, Stephen C; Birch, Paul R J; Govers, Francine; Kamoun, Sophien; van West, Pieter; Windass, John

2008-04-01

Much of the pathogenic success of Phytophthora infestans, the potato and tomato late blight agent, relies on its ability to generate from mycelia large amounts of sporangia, which release zoospores that encyst and form infection structures. To better understand these stages, Affymetrix GeneChips based on 15,650 unigenes were designed and used to profile the life cycle. Approximately half of P. infestans genes were found to exhibit significant differential expression between developmental transitions, with approximately (1)/(10) being stage-specific and most changes occurring during zoosporogenesis. Quantitative reverse-transcription polymerase chain reaction assays confirmed the robustness of the array results and showed that similar patterns of differential expression were obtained regardless of whether hyphae were from laboratory media or infected tomato. Differentially expressed genes encode potential cellular regulators, especially protein kinases; metabolic enzymes such as those involved in glycolysis, gluconeogenesis, or the biosynthesis of amino acids or lipids; regulators of DNA synthesis; structural proteins, including predicted flagellar proteins; and pathogenicity factors, including cell-wall-degrading enzymes, RXLR effector proteins, and enzymes protecting against plant defense responses. Curiously, some stage-specific transcripts do not appear to encode functional proteins. These findings reveal many new aspects of oomycete biology, as well as potential targets for crop protection chemicals.

Advances in Campylobacter biology and implications for biotechnological applications.

PubMed

Jeon, Byeonghwa; Muraoka, Wayne T; Zhang, Qijing

2010-05-01

Campylobacter jejuni is a major foodborne pathogen of animal origin and a leading cause of bacterial gastroenteritis in humans. During the past decade, especially since the publication of the first C. jejuni genome sequence, major advances have been made in understanding the pathobiology and physiology of this organism. It is apparent that C. jejuni utilizes sophisticated mechanisms for effective colonization of the intestinal tracts in various animal species. Although Campylobacter is fragile in the environment and requires fastidious growth conditions, it exhibits great flexibility in the adaptation to various habitats including the gastrointestinal tract. This high adaptability is attributable to its genetically, metabolically and phenotypically diverse population structure and its ability to change in response to various challenges. Unlike other enteric pathogens, such as Escherichia coli and Salmonella, Campylobacter is unable to utilize exogenous glucose and mainly depends on the catabolism of amino acids as a carbon source. Campylobacter proves highly mutable in response to antibiotic treatments and possesses eukaryote-like dual protein glycosylation systems, which modify flagella and other surface proteins with specific sugar structures. In this review we will summarize the distinct biological traits of Campylobacter and discuss the potential biotechnological approaches that can be developed to control this enteric pathogen. © 2009 The Authors. Journal compilation © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.

PubMed

Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A

2018-01-23

Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating spatial proximity analyses into other pathogenicity prediction tools may improve accuracy for other genes and genetic diseases.

Regulatory mechanisms of thiol-based redox sensors: lessons learned from structural studies on prokaryotic redox sensors.

PubMed

Lee, Sang Jae; Kim, Dong-Gyun; Lee, Kyu-Yeon; Koo, Ji Sung; Lee, Bong-Jin

2018-05-17

Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria. In general, oxidative molecules can induce changes in the three-dimensional structures of redox sensors, which, in turn, affects the transcription of specific genes in detoxification pathways and defense mechanisms. Moreover, pathogenic bacteria utilize these redox sensors for adaptation and to evade subsequent oxidative attacks from host immune defense. For this reason, the redox sensors of pathogenic bacteria are potential antibiotic targets. Understanding the regulatory mechanisms of thiol-based redox sensors in bacteria will provide insight and knowledge into the discovery of new antibiotics.

Task 1.5 Genomic Shift and Drift Trends of Emerging Pathogens

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

Borucki, M

2010-01-05

The Lawrence Livermore National Laboratory (LLNL) Bioinformatics group has recently taken on a role in DTRA's Transformation Medical Technologies Initiative (TMTI). The high-level goal of TMTI is to accelerate the development of broad-spectrum countermeasures. To achieve those goals, TMTI has a near term need to conduct analyses of genomic shift and drift trends of emerging pathogens, with a focused eye on select agent pathogens, as well as antibiotic and virulence markers. Most emerging human pathogens are zoonotic viruses with a genome composed of RNA. The high mutation rate of the replication enzymes of RNA viruses contributes to sequence drift andmore » provides one mechanism for these viruses to adapt to diverse hosts (interspecies transmission events) and cause new human and zoonotic diseases. Additionally, new viral pathogens frequently emerge due to genetic shift (recombination and segment reassortment) which allows for dramatic genotypic and phenotypic changes to occur rapidly. Bacterial pathogens also evolve via genetic drift and shift, although sequence drift generally occurs at a much slower rate for bacteria as compared to RNA viruses. However, genetic shift such as lateral gene transfer and inter- and intragenomic recombination enables bacteria to rapidly acquire new mechanisms of survival and antibiotic resistance. New technologies such as rapid whole genome sequencing of bacterial genomes, ultra-deep sequencing of RNA virus populations, metagenomic studies of environments rich in antibiotic resistance genes, and the use of microarrays for the detection and characterization of emerging pathogens provide mechanisms to address the challenges posed by the rapid emergence of pathogens. Bioinformatic algorithms that enable efficient analysis of the massive amounts of data generated by these technologies as well computational modeling of protein structures and evolutionary processes need to be developed to allow the technology to fulfill its potential.« less

High-risk febrile neutropenia in Auckland 2003-2004: the influence of the microbiology laboratory on patient treatment and the use of pathogen-specific therapy.

PubMed

Ritchie, S; Palmer, S; Ellis-Pegler, R

2007-01-01

International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result. The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003. One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy. Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection

PubMed Central

Ross, Caná L.; Spinler, Jennifer K.; Savidge, Tor C.

2016-01-01

Alteration of the gut microbial community structure and function through antibiotic use increases susceptibility to colonization by Clostridium difficile and other enteric pathogens. However, the mechanisms that mediate colonization resistance remain elusive. As the leading definable cause of infectious diarrhea, toxigenic C. difficile represents a burden for patients and health care systems, underscoring the need for better diagnostics and treatment strategies. Next-generation sequence data has increased our understanding of how the gut microbiota is influenced by many factors including diet, disease, aging and drugs. However, a microbial-based biomarker differentiating C. difficile infection from antibiotic-associated diarrhea remains elusive. Metabolomics profiling, which is highly responsive to changes in physiological conditions, have shown promise in differentiating subtle disease phenotypes that exhibit a nearly identical microbiome community structure, suggesting metabolite-based biomarkers may be an ideal diagnostic for identifying patients with CDI. This review focuses on the current understanding of structural and functional changes to the gut microbiota during C. difficile infection obtained from studies assessing the microbiome and metabolome of samples from patients and murine models. PMID:27180006

Western forest diseases and climate relations: Root diseases and climate change

Treesearch

Mee-Sook Kim; Bryce A. Richardson; Ned B. Klopfenstein

2008-01-01

Climate change could alter patterns of disturbances from pathogens through (1) direct effects on the development, survival, reproduction, dispersal, and distribution of pathogens; (2) physiological changes in tree defenses; (3) indirect effects from changes in the abundance of mutualists and competitors.

Heat treatment induced bacterial changes in irrigation water and their implications for plant disease management.

PubMed

Hao, W; Hong, C X

2014-05-01

A new heat treatment for recycled irrigation water using 48 °C for 24 h to inactivate Phytophthora and bacterial plant pathogens is estimated to reduce fuel cost and environmental footprint by more than 50 % compared to current protocol (95 °C for 30 s). The objective of this study was to determine the impact of this new heat treatment temperature regime on bacterial community structure in water and its practical implications. Bacterial communities in irrigation water were analyzed before and after heat treatment using both culture-dependent and -independent strategies based on the 16S ribosomal DNA. A significant shift was observed in the bacterial community after heat treatment. Most importantly, bacteria with biological control potential--Bacillus and Paenibacillus, and Pseudomonas species became more abundant at both 48 and 42 °C. These findings imply that the new heat treatment procedure not only controls existing plant pathogens but also may make the heat-treated irrigation water a more antagonistic environment against plant pathogens, promoting sustainable disease management.

Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

PubMed

Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

2017-01-01

Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

Interacting effects of land use and climate on rodent-borne pathogens in central Kenya.

PubMed

Young, Hillary S; McCauley, Douglas J; Dirzo, Rodolfo; Nunn, Charles L; Campana, Michael G; Agwanda, Bernard; Otarola-Castillo, Erik R; Castillo, Eric R; Pringle, Robert M; Veblen, Kari E; Salkeld, Daniel J; Stewardson, Kristin; Fleischer, Robert; Lambin, Eric F; Palmer, Todd M; Helgen, Kristofer M

2017-06-05

Understanding the effects of anthropogenic disturbance on zoonotic disease risk is both a critical conservation objective and a public health priority. Here, we evaluate the effects of multiple forms of anthropogenic disturbance across a precipitation gradient on the abundance of pathogen-infected small mammal hosts in a multi-host, multi-pathogen system in central Kenya. Our results suggest that conversion to cropland and wildlife loss alone drive systematic increases in rodent-borne pathogen prevalence, but that pastoral conversion has no such systematic effects. The effects are most likely explained both by changes in total small mammal abundance, and by changes in relative abundance of a few high-competence species, although changes in vector assemblages may also be involved. Several pathogens responded to interactions between disturbance type and climatic conditions, suggesting the potential for synergistic effects of anthropogenic disturbance and climate change on the distribution of disease risk. Overall, these results indicate that conservation can be an effective tool for reducing abundance of rodent-borne pathogens in some contexts (e.g. wildlife loss alone); however, given the strong variation in effects across disturbance types, pathogen taxa and environmental conditions, the use of conservation as public health interventions will need to be carefully tailored to specific pathogens and human contexts.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'. © 2017 The Authors.

Interacting effects of land use and climate on rodent-borne pathogens in central Kenya

PubMed Central

McCauley, Douglas J.; Dirzo, Rodolfo; Campana, Michael G.; Agwanda, Bernard; Otarola-Castillo, Erik R.; Castillo, Eric R.; Pringle, Robert M.; Veblen, Kari E.; Salkeld, Daniel J.; Stewardson, Kristin; Fleischer, Robert; Lambin, Eric F.; Palmer, Todd M.; Helgen, Kristofer M.

2017-01-01

Understanding the effects of anthropogenic disturbance on zoonotic disease risk is both a critical conservation objective and a public health priority. Here, we evaluate the effects of multiple forms of anthropogenic disturbance across a precipitation gradient on the abundance of pathogen-infected small mammal hosts in a multi-host, multi-pathogen system in central Kenya. Our results suggest that conversion to cropland and wildlife loss alone drive systematic increases in rodent-borne pathogen prevalence, but that pastoral conversion has no such systematic effects. The effects are most likely explained both by changes in total small mammal abundance, and by changes in relative abundance of a few high-competence species, although changes in vector assemblages may also be involved. Several pathogens responded to interactions between disturbance type and climatic conditions, suggesting the potential for synergistic effects of anthropogenic disturbance and climate change on the distribution of disease risk. Overall, these results indicate that conservation can be an effective tool for reducing abundance of rodent-borne pathogens in some contexts (e.g. wildlife loss alone); however, given the strong variation in effects across disturbance types, pathogen taxa and environmental conditions, the use of conservation as public health interventions will need to be carefully tailored to specific pathogens and human contexts. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’. PMID:28438909

Natural disturbance reduces disease risk in endangered rainforest frog populations

PubMed Central

Roznik, Elizabeth A.; Sapsford, Sarah J.; Pike, David A.; Schwarzkopf, Lin; Alford, Ross A.

2015-01-01

Natural disturbances can drive disease dynamics in animal populations by altering the microclimates experienced by hosts and their pathogens. Many pathogens are highly sensitive to temperature and moisture, and therefore small changes in habitat structure can alter the microclimate in ways that increase or decrease infection prevalence and intensity in host populations. Here we show that a reduction of rainforest canopy cover caused by a severe tropical cyclone decreased the risk of endangered rainforest frogs (Litoria rheocola) becoming infected by a fungal pathogen (Batrachochytrium dendrobatidis). Reductions in canopy cover increased the temperatures and rates of evaporative water loss in frog microhabitats, which reduced B. dendrobatidis infection risk in frogs by an average of 11–28% in cyclone-damaged areas, relative to unaffected areas. Natural disturbances to the rainforest canopy can therefore provide an immediate benefit to frogs by altering the microclimate in ways that reduce infection risk. This could increase host survival and reduce the probability of epidemic disease outbreaks. For amphibian populations under immediate threat from this pathogen, targeted manipulation of canopy cover could increase the availability of warmer, drier microclimates and therefore tip the balance from host extinction to coexistence. PMID:26294048

Natural disturbance reduces disease risk in endangered rainforest frog populations.

PubMed

Roznik, Elizabeth A; Sapsford, Sarah J; Pike, David A; Schwarzkopf, Lin; Alford, Ross A

2015-08-21

Natural disturbances can drive disease dynamics in animal populations by altering the microclimates experienced by hosts and their pathogens. Many pathogens are highly sensitive to temperature and moisture, and therefore small changes in habitat structure can alter the microclimate in ways that increase or decrease infection prevalence and intensity in host populations. Here we show that a reduction of rainforest canopy cover caused by a severe tropical cyclone decreased the risk of endangered rainforest frogs (Litoria rheocola) becoming infected by a fungal pathogen (Batrachochytrium dendrobatidis). Reductions in canopy cover increased the temperatures and rates of evaporative water loss in frog microhabitats, which reduced B. dendrobatidis infection risk in frogs by an average of 11-28% in cyclone-damaged areas, relative to unaffected areas. Natural disturbances to the rainforest canopy can therefore provide an immediate benefit to frogs by altering the microclimate in ways that reduce infection risk. This could increase host survival and reduce the probability of epidemic disease outbreaks. For amphibian populations under immediate threat from this pathogen, targeted manipulation of canopy cover could increase the availability of warmer, drier microclimates and therefore tip the balance from host extinction to coexistence.

A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection

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

Kaiser, Brooke LD; Li, Jie; Sanford, James A.

The potential for commensal microorganisms indigenous to a host (the ‘microbiome’ or ‘microbiota’) to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics “systems” approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alterationmore » of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium’s lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.« less

Crystal Structure of a Legionella pneumophila Ecto -Triphosphate Diphosphohydrolase, A Structural and Functional Homolog of the Eukaryotic NTPDases

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

Vivian, Julian P.; Riedmaier, Patrice; Ge, Honghua

2010-04-19

Many pathogenic bacteria have sophisticated mechanisms to interfere with the mammalian immune response. These include the disruption of host extracellular ATP levels that, in humans, is tightly regulated by the nucleoside triphosphate diphosphohydrolase family (NTPDases). NTPDases are found almost exclusively in eukaryotes, the notable exception being their presence in some pathogenic prokaryotes. To address the function of bacterial NTPDases, we describe the structures of an NTPDase from the pathogen Legionella pneumophila (Lpg1905/Lp1NTPDase) in its apo state and in complex with the ATP analog AMPPNP and the subtype-specific NTPDase inhibitor ARL 67156. Lp1NTPDase is structurally and catalytically related to eukaryotic NTPDasesmore » and the structure provides a basis for NTPDase-specific inhibition. Furthermore, we demonstrate that the activity of Lp1NTPDase correlates directly with intracellular replication of Legionella within macrophages. Collectively, these findings provide insight into the mechanism of this enzyme and highlight its role in host-pathogen interactions.« less

Competition for attachment of aquaculture candidate probiotic and pathogenic bacteria on fish intestinal mucus.

PubMed

Vine, N G; Leukes, W D; Kaiser, H; Daya, S; Baxter, J; Hecht, T

2004-06-01

Probiotics for aquaculture are generally only selected by their ability to produce antimicrobial metabolites; however, attachment to intestinal mucus is important in order to remain within the gut of its host. Five candidate probiotics (AP1-AP5), isolated from the clownfish, Amphiprion percula (Lacepéde), were examined for their ability to attach to fish intestinal mucus and compete with two pathogens, Aeromonas hydrophila and Vibrio alginolyticus. Two different radioactive isotopes were used to quantify competition between pathogens and probionts. Attachment of the pathogens was enhanced by the presence of the candidate probiotics. However, the addition of the candidate probiotics after the pathogens resulted in reduced pathogen attachment. Only AP5 caused lower attachment success of V. alginolyticus when added before the pathogen. When AP5 was added first, the average attachment change was 41% compared with 72% when added after V. alginolyticus, suggesting that the probiotic is displaced but that enhanced attachment of the pathogen does not occur. Conversely, when V. alginolyticus was added first, followed by AP5, attachment change was 37% while AP5 had 92% attachment change when added second. This implies that the pathogen was displaced by the candidate probiotic and therefore it appeared that, based on the ability of probiont AP5 to attach to mucus, the growth of the pathogen in the digestive tract might be suppressed by the candidate probiont's presence.

Role of stochastic processes in maintaining discrete strain structure in antigenically diverse pathogen populations.

PubMed

Buckee, Caroline O; Recker, Mario; Watkins, Eleanor R; Gupta, Sunetra

2011-09-13

Many highly diverse pathogen populations appear to exist stably as discrete antigenic types despite evidence of genetic exchange. It has been shown that this may arise as a consequence of immune selection on pathogen populations, causing them to segregate permanently into discrete nonoverlapping subsets of antigenic variants to minimize competition for available hosts. However, discrete antigenic strain structure tends to break down under conditions where there are unequal numbers of allelic variants at each locus. Here, we show that the inclusion of stochastic processes can lead to the stable recovery of discrete strain structure through loss of certain alleles. This explains how pathogen populations may continue to behave as independently transmitted strains despite inevitable asymmetries in allelic diversity of major antigens. We present evidence for this type of structuring across global meningococcal isolates in three diverse antigens that are currently being developed as vaccine components.

Relationship between Chemical Structure and Antimicrobial Activities of Isothiocyanates from Cruciferous Vegetables against Oral Pathogens.

PubMed

Ko, Mi-Ok; Kim, Mi-Bo; Lim, Sang-Bin

2016-12-28

We evaluated the potentials of 10 isothiocyanates (ITCs) from cruciferous vegetables and radish root hydrolysate for inhibiting the growth of oral pathogens, with an emphasis on assessing any structure-function relationship. Structural differences in ITCs impacted their antimicrobial activities against oral pathogens differently. The indolyl ITC (indol-3-carbinol) was the most potent inhibitor of the growth of oral pathogens, followed by aromatic ITCs (benzyl ITC (BITC) and phenylethyl ITC (PEITC)) and aliphatic ITCs (erucin, iberin, and sulforaphene). Sulforaphene, which is similar in structure, but has one double bond, showed higher antimicrobial activity than sulforaphane. Erucin, which has a thiol group, showed higher antimicrobial activity than sulforaphane, which has a sulfinyl group. BITC and iberin with a short chain exhibited higher antimicrobial potential than PEITC and sulforaphane with a longer chain, respectively. ITCs have strong antimicrobial activities and may be useful in the prevention and management of dental caries.

Calling in sick: impacts of fever on intra-urban human mobility.

PubMed

Perkins, T Alex; Paz-Soldan, Valerie A; Stoddard, Steven T; Morrison, Amy C; Forshey, Brett M; Long, Kanya C; Halsey, Eric S; Kochel, Tadeusz J; Elder, John P; Kitron, Uriel; Scott, Thomas W; Vazquez-Prokopec, Gonzalo M

2016-07-13

Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A retrospective, semi-structured interview allowed us to quantify multiple aspects of mobility during the two-week period preceding each interview. We fitted nested models of each aspect of mobility to data from interviews and compared models using likelihood ratio tests to determine whether there were statistically distinguishable differences in mobility attributable to fever or its aetiology. Compared with afebrile individuals, febrile study participants spent more time at home, visited fewer locations, and, in some cases, visited locations closer to home and spent less time at certain types of locations. These multifaceted impacts are consistent with the possibility that disease-mediated changes in host mobility generate dynamic and complex changes in host contact network structure. © 2016 The Author(s).

Calling in sick: impacts of fever on intra-urban human mobility

PubMed Central

Perkins, T. Alex; Paz-Soldan, Valerie A.; Stoddard, Steven T.; Morrison, Amy C.; Forshey, Brett M.; Long, Kanya C.; Halsey, Eric S.; Kochel, Tadeusz J.; Elder, John P.; Kitron, Uriel; Scott, Thomas W.; Vazquez-Prokopec, Gonzalo M.

2016-01-01

Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A retrospective, semi-structured interview allowed us to quantify multiple aspects of mobility during the two-week period preceding each interview. We fitted nested models of each aspect of mobility to data from interviews and compared models using likelihood ratio tests to determine whether there were statistically distinguishable differences in mobility attributable to fever or its aetiology. Compared with afebrile individuals, febrile study participants spent more time at home, visited fewer locations, and, in some cases, visited locations closer to home and spent less time at certain types of locations. These multifaceted impacts are consistent with the possibility that disease-mediated changes in host mobility generate dynamic and complex changes in host contact network structure. PMID:27412286

Direct and indirect effects of climate change on the risk of infection by water-transmitted pathogens.

PubMed

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

2013-11-19

Climate change is likely to affect the infectious disease burden from exposure to pathogens in water used for drinking and recreation. Effective intervention measures require quantification of impacts of climate change on the distribution of pathogens in the environment and their potential effects on human health. Objectives of this systematic review were to summarize current knowledge available to estimate how climate change may directly and indirectly affect infection risks due to Campylobacter, Cryptosporidium, norovirus, and Vibrio. Secondary objectives were to prioritize natural processes and interactions that are susceptible to climate change and to identify knowledge gaps. Search strategies were determined based on a conceptual model and scenarios with the main emphasis on The Netherlands. The literature search resulted in a large quantity of publications on climate variables affecting pathogen input and behavior in aquatic environments. However, not all processes and pathogens are evenly covered by the literature, and in many cases, the direction of change is still unclear. To make useful predictions of climate change, it is necessary to combine both negative and positive effects. This review provides an overview of the most important effects of climate change on human health and shows the importance of QMRA to quantify the net effects.

Effect of temperature and colonization of Legionella pneumophila and Vermamoeba vermiformis on bacterial community composition of copper drinking water biofilms.

PubMed

Buse, Helen Y; Ji, Pan; Gomez-Alvarez, Vicente; Pruden, Amy; Edwards, Marc A; Ashbolt, Nicholas J

2017-07-01

It is unclear how the water-based pathogen, Legionella pneumophila (Lp), and associated free-living amoeba (FLA) hosts change or are changed by the microbial composition of drinking water (DW) biofilm communities. Thus, this study characterized the bacterial community structure over a 7-month period within mature (> 600-day-old) copper DW biofilms in reactors simulating premise plumbing and assessed the impact of temperature and introduction of Lp and its FLA host, Vermamoeba vermiformis (Vv), co-cultures (LpVv). Sequence and quantitative PCR (qPCR) analyses indicated a correlation between LpVv introduction and increases in Legionella spp. levels at room temperature (RT), while at 37°C, Lp became the dominant Legionella spp. qPCR analysis suggested Vv presence may not be directly associated with Lp biofilm growth at RT and 37°C, but may contribute to or be associated with non-Lp legionellae persistence at RT. Two-way PERMANOVA and PCoA revealed that temperature was a major driver of microbiome diversity. Biofilm community composition also changed over the seven-month period and could be associated with significant shifts in dissolved oxygen, alkalinity and various metals in the influent DW. Hence, temperature, biofilm age, DW quality and transient intrusions/amplification of pathogens and FLA hosts may significantly impact biofilm microbiomes and modulate pathogen levels over extended periods. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Drivers, dynamics, and control of emerging vector-borne zoonotic diseases

PubMed Central

Kilpatrick, A. Marm; Randolph, Sarah E.

2013-01-01

Emerging vector-borne diseases represent an important issue for global health. Many vector-borne pathogens have appeared in new regions in the past two decades, and many endemic diseases have increased in incidence. Although introductions and local emergence are frequently considered distinct processes, many emerging endemic pathogens are in fact invading at a local scale coincident with habitat change. We highlight key differences in the dynamics and disease burden that result from increased pathogen transmission following habitat change compared with the introduction of pathogens to new regions. Truly in situ emergence is commonly driven by changes in human factors as much as by enhanced enzootic cycles whereas pathogen invasion results from anthropogenic trade and travel and suitable conditions for a pathogen, including hosts, vectors, and climate. Once established, ecological factors related to vector characteristics shape the evolutionary selective pressure on pathogens that may result in increased use of humans as transmission hosts. We describe challenges inherent in the control of vector-borne zoonotic diseases and some emerging non-traditional strategies that may be more effective in the long term. PMID:23200503

Genetic reprogramming of host cells by bacterial pathogens.

PubMed

Tran Van Nhieu, Guy; Arbibe, Laurence

2009-10-29

During the course of infection, pathogens often induce changes in gene expression in host cells and these changes can be long lasting and global or transient and of limited amplitude. Defining how, when, and why bacterial pathogens reprogram host cells represents an exciting challenge that opens up the opportunity to grasp the essence of pathogenesis and its molecular details.

Biomimetic virus-based colourimetric sensors.

PubMed

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.

Biomimetic virus-based colourimetric sensors

NASA Astrophysics Data System (ADS)

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.

Using impedance measurements for detecting pathogens trapped in an electric field

DOEpatents

Miles, Robin R.

2004-07-20

Impedance measurements between the electrodes in an electric field is utilized to detect the presence of pathogens trapped in the electric field. Since particles trapped in a field using the dielectiphoretic force changes the impedance between the electrodes by changing the dielectric material between the electrodes, the degree of particle trapping can be determined by measuring the impedance. This measurement is used to determine if sufficient pathogen have been collected to analyze further or potentially to identify the pathogen.

Climate Change, Foodborne Pathogens and Illness in Higher-Income Countries.

PubMed

Lake, I R; Barker, G C

2018-03-01

We present a review of the likely consequences of climate change for foodborne pathogens and associated human illness in higher-income countries. The relationships between climate and food are complex and hence the impacts of climate change uncertain. This makes it difficult to know which foodborne pathogens will be most affected, what the specific effects will be, and on what timescales changes might occur. Hence, a focus upon current capacity and adaptation potential against foodborne pathogens is essential. We highlight a number of developments that may enhance preparedness for climate change. These include the following: Adoption of novel surveillance methods, such as syndromic methods, to speed up detection and increase the fidelity of intervention in foodborne outbreaks Genotype-based approaches to surveillance of food pathogens to enhance spatiotemporal resolution in tracing and tracking of illness Ever increasing integration of plant, animal and human surveillance systems, One Health, to maximise potential for identifying threats Increased commitment to cross-border (global) information initiatives (including big data) Improved clarity regarding the governance of complex societal issues such as the conflict between food safety and food waste Strong user-centric (social) communications strategies to engage diverse stakeholder groups The impact of climate change upon foodborne pathogens and associated illness is uncertain. This emphasises the need to enhance current capacity and adaptation potential against foodborne illness. A range of developments are explored in this paper to enhance preparedness.

Effect of climate change on runoff of Campylobacter and Cryptosporidium from land to surface water.

PubMed

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

2016-05-15

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, for instance, bathing or drinking-water consumption. An increase in runoff, and associated wash-off of animal faeces from fields, is assumed to contribute to the increase of disease outbreaks during periods of high precipitation. Climate change is expected to increase winter precipitation and extreme precipitation events during summer, but has simultaneously also other effects such as temperature rise and changes in evapotranspiration. The question is to what extent the combination of these effects influence the input of zoonotic pathogens to the surface waters. To quantitatively analyse the impacts of climate change on pathogen runoff, pathogen concentrations reaching surface waters through runoff were calculated by combining an input model for catchment pathogen loads with the Wageningen Lowland Runoff Simulator (WALRUS). Runoff of Cryptosporidium and Campylobacter was evaluated under different climate change scenarios and by applying different scenarios for sources of faecal pollution in the catchments, namely dairy cows and geese and manure fertilization. Model evaluation of these scenarios shows that climate change has little overall impact on runoff of Campylobacter and Cryptosporidium from land to the surface waters. Even though individual processes like runoff fluxes, pathogen release and dilution are affected, either positively or negatively, the net effect on the pathogen concentration in surface waters and consequently also on infection risks through recreation seems limited. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Implication of global climate change on the distribution and activity of Phytophthora ramorum

Treesearch

Robert C. Venette

2009-01-01

Global climate change is predicted to alter the distribution and activity of several forest pathogens. Boland et al. (2004) suggested that climate change might affect pathogen establishment, rate of disease progress, and the duration of...

Stand-structural effects on Heterobasidion abietinum-related mortality following drought events in Abies pinsapo.

PubMed

Linares, Juan Carlos; Camarero, Jesús Julio; Bowker, Matthew A; Ochoa, Victoria; Carreira, José Antonio

2010-12-01

Climate change may affect tree-pathogen interactions. This possibility has important implications for drought-prone forests, where stand dynamics and disease pathogenicity are especially sensitive to climatic stress. In addition, stand structural attributes including density-dependent tree-to-tree competition may modulate the stands' resistance to drought events and pathogen outbreaks. To assess the effects of stand structure on root-rot-related mortality after severe droughts, we focused on Heterobasidion abietinum mortality in relict Spanish stands of Abies pinsapo, a drought-sensitive fir. We compared stand attributes and tree spatial patterns in three plots with H. abietinum root-rot disease and three plots without root-rot. Point-pattern analyses were used to investigate the scale and extent of mortality patterns and to test hypotheses related to the spread of the disease. Dendrochronology was used to date the year of death and to assess the association between droughts and growth decline. We applied a structural equation modelling approach to test if tree mortality occurs more rapidly than predicted by a simple distance model when trees are subjected to high tree-to-tree competition and following drought events. Contrary to expectations of drought mortality, the effect of precipitation on the year of death was strong and negative, indicating that a period of high precipitation induced an earlier tree death. Competition intensity, related to the size and density of neighbour trees, also induced an earlier tree death. The effect of distance to the disease focus was negligible except in combination with intensive competition. Our results indicate that infected trees have decreased ability to withstand drought stress, and demonstrate that tree-to-tree competition and fungal infection act as predisposing factors of forest decline and mortality.

Plant-Pathogen Warfare under Changing Climate Conditions.

PubMed

Velásquez, André C; Castroverde, Christian Danve M; He, Sheng Yang

2018-05-21

Global environmental changes caused by natural and human activities have accelerated in the past 200 years. The increase in greenhouse gases is predicted to continue to raise global temperature and change water availability in the 21 st century. In this Review, we explore the profound effect the environment has on plant diseases - a susceptible host will not be infected by a virulent pathogen if the environmental conditions are not conducive for disease. The change in CO 2 concentrations, temperature, and water availability can have positive, neutral, or negative effects on disease development, as each disease may respond differently to these variations. However, the concept of disease optima could potentially apply to all pathosystems. Plant resistance pathways, including pattern-triggered immunity to effector-triggered immunity, RNA interference, and defense hormone networks, are all affected by environmental factors. On the pathogen side, virulence mechanisms, such as the production of toxins and virulence proteins, as well as pathogen reproduction and survival are influenced by temperature and humidity. For practical reasons, most laboratory investigations into plant-pathogen interactions at the molecular level focus on well-established pathosystems and use a few static environmental conditions that capture only a fraction of the dynamic plant-pathogen-environment interactions that occur in nature. There is great need for future research to increasingly use dynamic environmental conditions in order to fully understand the multidimensional nature of plant-pathogen interactions and produce disease-resistant crop plants that are resilient to climate change. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thienopyrimidine-type compounds protect Arabidopsis plants against the hemibiotrophic fungal pathogen Colletotrichum higginsianum and bacterial pathogen Pseudomonas syringae pv. maculicola.

PubMed

Narusaka, Mari; Narusaka, Yoshihiro

2017-03-04

Plant activators activate systemic acquired resistance-like defense responses or induced systemic resistance, and thus protect plants from pathogens. We screened a chemical library composed of structurally diverse small molecules. We isolated six plant immune-inducing thienopyrimidine-type compounds and their analogous compounds. It was observed that the core structure of thienopyrimidine plays a role in induced resistance in plants. Furthermore, we highlight the protective effect of thienopyrimidine-type compounds against both hemibiotrophic fungal pathogen, Colletotrichum higginsianum, and bacterial pathogen, Pseudomonas syringae pv. maculicola, in Arabidopsis thaliana. We suggest that thienopyrimidine-type compounds could be potential lead compounds as novel plant activators, and can be useful and effective agrochemicals against various plant diseases.

Recent progress in elucidating the structure, function and evolution of disease resistance genes in plants.

PubMed

Liu, Jinling; Liu, Xionglun; Dai, Liangying; Wang, Guoliang

2007-09-01

Plants employ multifaceted mechanisms to fight with numerous pathogens in nature. Resistance (R) genes are the most effective weapons against pathogen invasion since they can specifically recognize the corresponding pathogen effectors or associated protein(s) to activate plant immune responses at the site of infection. Up to date, over 70 R genes have been isolated from various plant species. Most R proteins contain conserved motifs such as nucleotide-binding site (NBS), leucine-rich repeat (LRR), Toll-interleukin-1 receptor domain (TIR, homologous to cytoplasmic domains of the Drosophila Toll protein and the mammalian interleukin-1 receptor), coiled-coil (CC) or leucine zipper (LZ) structure and protein kinase domain (PK). Recent results indicate that these domains play significant roles in R protein interactions with effector proteins from pathogens and in activating signal transduction pathways involved in innate immunity. This review highlights an overview of the recent progress in elucidating the structure, function and evolution of the isolated R genes in different plant-pathogen interaction systems.

Pathogenic marine microbes influence the effects of climate change on a commercially important tropical bivalve.

PubMed

Turner, Lucy M; Alsterberg, Christian; Turner, Andrew D; Girisha, S K; Rai, Ashwin; Havenhand, Jonathan N; Venugopal, M N; Karunasagar, Indrani; Godhe, Anna

2016-08-31

There is growing evidence that climate change will increase the prevalence of toxic algae and harmful bacteria, which can accumulate in marine bivalves. However, we know little about any possible interactions between exposure to these microorganisms and the effects of climate change on bivalve health, or about how this may affect the bivalve toxin-pathogen load. In mesocosm experiments, mussels, Perna viridis, were subjected to simulated climate change (warming and/or hyposalinity) and exposed to harmful bacteria and/or toxin-producing dinoflagellates. We found significant interactions between climate change and these microbes on metabolic and/or immunobiological function and toxin-pathogen load in mussels. Surprisingly, however, these effects were virtually eliminated when mussels were exposed to both harmful microorganisms simultaneously. This study is the first to examine the effects of climate change on determining mussel toxin-pathogen load in an ecologically relevant, multi-trophic context. The results may have considerable implications for seafood safety.

Influence of silver nanoparticles on food components in wheat

NASA Astrophysics Data System (ADS)

Nawrocka, A.; Cieśla, J.

2013-01-01

During storage, grain might be affected by bacterial and fungal infections. Pathogens diminish the grain quality through contamination with excrements and second metabolites. It is very important to prevent grain from infections. Due to their antimicrobial properties, silver nanoparticles can play the role of an effective protector. The influence of nanoparticles on wheat quality was studied. The gluten parameters and falling number did not change after covering the grain with silver nanoparticles stabilized by sodium citrate. Changes in the structure of starch and gluten were investigated using Fourier-transform infrared spectroscopy. Infrared spectra of the whole meal and starch have shown a slight shift (from 1 000 to 995cm-1) of the band connected with the C-O-H bending. This displacement is probably related to the changes in sample moisture. Significant differences, corresponding to changes in the protein secondary structure, have appeared in the gluten spectra after covering.A decrease of absorbance in the amide and CH and OH regions has been observed regardless of the covering time.

Forest legacies, climate change, altered disturbance regimes, invasive species and water

USGS Publications Warehouse

Stohlgren, T.; Jarnevich, C.; Kumar, S.

2007-01-01

The factors that must be considered in seeking to predict changes in water availability has been examined. These factors are the following: forest legacies including logging, mining, agriculture, grazing, elimination of large carnivores, human-caused wildfire, and pollution; climate change and stream flow; altered disturbances such as frequency intensity and pattern of wildfires and insect outbreaks as well as flood control; lastly, invasive species like forest pests and pathogens. An integrated approach quantifying the current and past condition trends can be combined with spatial and temporal modeling to develop future change in forest structures and water supply. The key is a combination of geographic information system technologies with climate and land use scenarios, while preventing and minimizing the effects of harmful invasive species.

Human soil-borne pathogens and risks associated with land use change

NASA Astrophysics Data System (ADS)

Pereg, Lily

2017-04-01

Soil is a source of pathogenic, neutral and beneficial microorganisms. Natural events and anthropogenic activity can affect soil biodiversity and influence the balance and distribution of soil-borne human pathogens. Important bacterial and fungal pathogens, such as Bacillus anthracis, Coxiella bernetii, Clostridium tetani, Escherichia coli 0157:H7, Listeria monocytogenes, Aspergillus fumigatus and Sporothrix schenckii will be discussed. This presentation will concentrate on soil pathogenic microorganisms and the effects of land use change on their prevalence and distribution. In particular, the potential of agricultural soil cultivation to enhance pathogen transmission to human through the release of soil microbes into the air attached to dust particles, contamination of waterways and infection of food plants and animal. Emerging solutions, such as biocontrol and probiotics, will be discussed.

Analysis of bacterial communities and bacterial pathogens in a biogas plant by the combination of ethidium monoazide, PCR and Ion Torrent sequencing.

PubMed

Luo, Gang; Angelidaki, Irini

2014-09-01

The present study investigated the changes of bacterial community composition including bacterial pathogens along a biogas plant, i.e. from the influent, to the biogas reactor and to the post-digester. The effects of post-digestion temperature and time on the changes of bacterial community composition and bacterial pathogens were also studied. Microbial analysis was made by Ion Torrent sequencing of the PCR amplicons from ethidium monoazide treated samples, and ethidium monoazide was used to cleave DNA from dead cells and exclude it from PCR amplification. Both similarity and taxonomic analysis showed that the bacterial community composition in the influent was changed after anaerobic digestion. Firmicutes were dominant in all the samples, while Proteobacteria decreased in the biogas reactor compared with the influent. Variations of bacterial community composition in the biogas reactor with time were also observed. This could be attributed to varying composition of the influent. Batch experiments showed that the methane recovery from the digested residues (obtained from biogas reactor) was mainly related with post-digestion temperature. However, post-digestion time rather than temperature had a significant effect on the changes of bacterial community composition. The changes of bacterial community composition were also reflected in the changes of relative abundance of bacterial pathogens. The richness and relative abundance of bacterial pathogens were reduced after anaerobic digestion in the biogas reactor. It was found in batch experiments that bacterial pathogens showed the highest relative abundance and richness after 30 days' post-digestion. Streptococcus bovis was found in all the samples. Our results showed that special attention should be paid to the post-digestion since the increase in relative abundance of bacterial pathogens after post-digestion might reflect regrowth of bacterial pathogens and limit biosolids disposal vectors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Geostatistical analysis of data on air temperature and plant phenology from Baden-Württemberg (Germany) as a basis for regional scaled models of climate change.

PubMed

Schröder, Winfried; Schmidt, Gunther; Hasenclever, Judith

2006-09-01

The rise of the air temperature is assured to be part of the global climatic change, but there is still a lack of knowledge about its effects at a regional scale. The article tackles the correlation of air temperature with the phenology of selected plants by the example of Baden-Württemberg to provide a spatial valid data base for regional climate change models. To this end, the data on air temperature and plant phenology, gathered from measurement sites without congruent coverage, were correlated after performing geostatistical analysis and estimation. In addition, geostatistics are used to analyze and cartographically depict the spatial structure of the phenology of plants in spring and in summer. The statistical analysis reveals a significant relationship between the rising air temperature and the earlier beginning of phenological phases like blooming or fruit maturation: From 1991 to 1999 spring time, as indicated by plant phenology, has begun up to 15 days earlier than from 1961 to 1990. As shown by geostatistics, this holds true for the whole territory of Baden-Württemberg. The effects of the rise of air temperature should be investigated not only by monitoring biological individuals, as for example plants, but on an ecosystem level as well. In Germany, the environmental monitoring should be supplemented by the study of the effects of the climatic change in ecosystems. Because air temperature and humidity have a great influence on the temporal and spatial distribution of pathogen carriers (vectors) and pathogens, mapping of the environmental determinants of vector and pathogen distribution in space and time should be performed in order to identify hot spots for risk assessment and further detailed epidemiological studies.

Spatial modelling of the potential temperature-dependent transmission of vector-associated diseases in the face of climate change: main results and recommendations from a pilot study in Lower Saxony (Germany).

PubMed

Schröder, Winfried; Schmidt, Gunther

2008-12-01

The sustained climate change is going to modify the geographic distribution, the seasonal transmission gate and the intensity of the transmission of vector-borne diseases such as malaria or the bluetongue disease. These diseases occur nowadays at higher latitudes or altitudes. A further rise in ambient temperature and rainfall will extend the duration of the season in which mosquito vectors are transmitting pathogens. The parasites transmitted by the vectors also benefit from increasing temperatures, as both their reproduction and development are then accelerated, too. Thus, it seemed prudent to examine potential effects on the seasonal transmission gate due to the ongoing and predicted climate changes. Lower Saxony (northwest Germany) is a former malaria region with highest incidences of Anopheles atroparvus and tertian malaria along the coastal zones before malaria had finally become extinct in the early 1950s. Nevertheless, the Anopheles mosquitoes which transmit the malaria pathogens have still been present in Lower Saxony up to now. This together with the climate change-related implications gave reason to investigate whether a new autochthonous transmission could take place if the malaria pathogen is introduced again in Lower Saxony. Thus, the potential spatial and temporal structure of temperature-driven malaria transmissions was mapped using the basic reproduction rate (R (0)) and measured and predicted air temperatures (1947-1960, 1961-1990, 1985-2004, 2020, 2060, 2100, each best case and worst case scenario). This paper focuses on both the summarizing of the results from this risk modelling approach and on the conclusions to be drawn. The recommendations highlight the need to link vector monitoring as one of the key elements of an epidemiological monitoring with the environmental monitoring.

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

PubMed

Heinz, Franz X; Stiasny, Karin

2017-03-01

Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. Copyright © 2017 American Society for Microbiology.

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis

PubMed Central

Stiasny, Karin

2017-01-01

SUMMARY Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization. PMID:28179396

Synthetic analogs of bacterial quorum sensors

DOEpatents

Iyer, Rashi [Los Alamos, NM; Ganguly, Kumkum [Los Alamos, NM; Silks, Louis A [Los Alamos, NM

2011-12-06

Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

Synthetic analogs of bacterial quorum sensors

DOEpatents

Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

2013-01-08

Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

Conversion from long-term cultivated wheat field to Jerusalem artichoke plantation changed soil fungal communities

NASA Astrophysics Data System (ADS)

Zhou, Xingang; Zhang, Jianhui; Gao, Danmei; Gao, Huan; Guo, Meiyu; Li, Li; Zhao, Mengliang; Wu, Fengzhi

2017-01-01

Understanding soil microbial communities in agroecosystems has the potential to contribute to the improvement of agricultural productivity and sustainability. Effects of conversion from long-term wheat plantation to Jerusalem artichoke (JA) plantation on soil fungal communities were determined by amplicon sequencing of total fungal ITS regions. Quantitative PCR and PCR-denaturing gradient gel electrophoresis were also used to analyze total fungal and Trichoderma spp. ITS regions and Fusarium spp. Ef1α genes. Results showed that soil organic carbon was higher in the first cropping of JA and Olsen P was lower in the third cropping of JA. Plantation conversion changed soil total fungal and Fusarium but not Trichoderma spp. community structures and compositions. The third cropping of JA had the lowest total fungal community diversity and Fusarium spp. community abundance, but had the highest total fungal and Trichoderma spp. community abundances. The relative abundances of potential fungal pathogens of wheat were higher in the wheat field. Fungal taxa with plant growth promoting, plant pathogen or insect antagonistic potentials were enriched in the first and second cropping of JA. Overall, short-term conversion from wheat to JA plantation changed soil fungal communities, which is related to changes in soil organic carbon and Olsen P contents.

Conversion from long-term cultivated wheat field to Jerusalem artichoke plantation changed soil fungal communities

PubMed Central

Zhou, Xingang; Zhang, Jianhui; Gao, Danmei; Gao, Huan; Guo, Meiyu; Li, Li; Zhao, Mengliang; Wu, Fengzhi

2017-01-01

Understanding soil microbial communities in agroecosystems has the potential to contribute to the improvement of agricultural productivity and sustainability. Effects of conversion from long-term wheat plantation to Jerusalem artichoke (JA) plantation on soil fungal communities were determined by amplicon sequencing of total fungal ITS regions. Quantitative PCR and PCR-denaturing gradient gel electrophoresis were also used to analyze total fungal and Trichoderma spp. ITS regions and Fusarium spp. Ef1α genes. Results showed that soil organic carbon was higher in the first cropping of JA and Olsen P was lower in the third cropping of JA. Plantation conversion changed soil total fungal and Fusarium but not Trichoderma spp. community structures and compositions. The third cropping of JA had the lowest total fungal community diversity and Fusarium spp. community abundance, but had the highest total fungal and Trichoderma spp. community abundances. The relative abundances of potential fungal pathogens of wheat were higher in the wheat field. Fungal taxa with plant growth promoting, plant pathogen or insect antagonistic potentials were enriched in the first and second cropping of JA. Overall, short-term conversion from wheat to JA plantation changed soil fungal communities, which is related to changes in soil organic carbon and Olsen P contents. PMID:28134269

The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

PubMed Central

Walley, Justin W.; Rowe, Heather C.; Xiao, Yanmei; Chehab, E. Wassim; Kliebenstein, Daniel J.; Wagner, Doris; Dehesh, Katayoon

2008-01-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks. PMID:19079584

The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

PubMed

Walley, Justin W; Rowe, Heather C; Xiao, Yanmei; Chehab, E Wassim; Kliebenstein, Daniel J; Wagner, Doris; Dehesh, Katayoon

2008-12-01

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

Structure, Biology, and Therapeutic Application of Toxin-Antitoxin Systems in Pathogenic Bacteria.

PubMed

Lee, Ki-Young; Lee, Bong-Jin

2016-10-22

Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein-protein interactions. Accumulating knowledge about the structure-function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.

Evaluation of blood and bone marrow in selected canine vector-borne diseases.

PubMed

De Tommasi, Anna S; Otranto, Domenico; Furlanello, Tommaso; Tasca, Silvia; Cantacessi, Cinzia; Breitschwerdt, Edward B; Stanneck, Dorothee; Dantas-Torres, Filipe; Baneth, Gad; Capelli, Gioia; de Caprariis, Donato

2014-12-02

Bone marrow (BM) is a major hematopoietic organ that can harbour a variety of vector-borne pathogens; however, knowledge of BM pathological changes in dogs infected with vector-borne pathogens is limited. Thus, the aim of the present study was to assess the pathological changes in canine BM associated with natural infections by four vector-borne pathogens, as well as to determine the relationships between such changes and abnormalities of the peripheral blood. Cytological disorders and pathological changes of the BM of 83 dogs naturally-infected with one or more of four vector-borne pathogens (i.e., Anaplasma platys, Leishmania infantum, Babesia vogeli and Hepatozoon canis) were evaluated and compared with the corresponding hematological findings. Dysgranulopoiesis and dysmegakaryocytopoiesis were the most frequently observed BM abnormalities in infected dogs. Erythroid suppression, and lymphocytic, monocytic and macrophage hyperplasia were also observed. Interestingly, associations between suppression and hyperplasia of specific cell lines in the marrow and corresponding changes in numbers of circulating peripheral blood cells were not observed. Infections with one or more of the vector-borne pathogens examined in this study should be considered as differential diagnoses for secondary dysmyelopoiesis.

Cryo-EM of the pathogenic VCP variant R155P reveals long-range conformational changes in the D2 ATPase ring

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

Mountassif, Driss; Fabre, Lucien; Zaid, Younes

Single amino acid mutations in valosin containing protein (VCP/p97), a highly conserved member of the ATPases associated with diverse cellular activities (AAA) family of ATPases has been linked to a severe degenerative disease affecting brain, muscle and bone tissue. Previous studies have demonstrated the role of VCP mutations in altering the ATPase activity of the D2 ring; however the structural consequences of these mutations remain unclear. In this study, we report the three-dimensional (3D) map of the pathogenic VCP variant, R155P, as revealed by single-particle Cryo-Electron Microscopy (EM) analysis at 14 Å resolution. We show that the N-terminal R155P mutation inducesmore » a large structural reorganisation of the D2 ATPase ring. Results from docking studies using crystal structure data of available wild-type VCP in the EM density maps indicate that the major difference is localized at the interface between two protomers within the D2 ring. Consistent with a conformational change, the VCP R155P variant shifted the isoelectric point of the protein and reduced its interaction with its well-characterized cofactor, nuclear protein localization-4 (Npl4). Together, our results demonstrate that a single amino acid substitution in the N-terminal domain can relay long-range conformational changes to the distal D2 ATPase ring. Our results provide the first structural clues of how VCP mutations may influence the activity and function of the D2 ATPase ring. - Highlights: • p97{sub R155P} and p97{sub A232E} decrease the ability of p97 to bind to its co-factor Npl4. • p97{sub R155P} has a different isoelectric point than that of p97{sub R95G}, p97{sub A232E} and p97{sub WT}. • Mutation R155P changes principally the conformation of the D2 ring. • Mutation R155P modifies the interface between two protomers within the D2 ring.« less

Gall-ID: Tools for genotyping gall-causing phytopathogenic bacteria

USDA-ARS?s Scientific Manuscript database

Understanding the population structure and genetic diversity of plant pathogens, as well as the effect of agricultural practices on pathogen evolution, are important for disease management. Developments in molecular methods have contributed to increasing the resolution for accurate pathogen identifi...

Evaluation of nanoparticles as endocytic tracers in cellular microbiology

NASA Astrophysics Data System (ADS)

Zhang, Yuying; Hensel, Michael

2013-09-01

The study of pathogen interactions with eukaryotic host cells requires the introduction of fluorescent probes to visualize processes such as endocytosis, intracellular transport or host cell manipulation by the pathogen. Here, three types of fluorescent nanoparticles (NPs), i.e. Rhodamine-labeled polymethacrylate (PMA) NPs, silica NPs and gold NPs, were employed to label the host cellular endolysosomal system and monitor manipulations by the pathogen Salmonella enterica. Using live cell imaging, we investigated the performance of NPs in cellular uptake, labeling of endocytic vesicles and lysosomes, as well as interaction with the pathogen. We show that fluorescent gold and silica, but not PMA NPs appropriately label host cell structures and efficiently track rearrangements of the host endosomal system by the activities of intracellular Salmonella. Silica NPs slightly aggregated and located in Salmonella-induced compartments as isolated dots, while gold NPs distributed uniformly inside such structures. Both silica and gold NPs exhibited no adverse impact on either host cells or pathogens, and are versatile tools for infection biology.The study of pathogen interactions with eukaryotic host cells requires the introduction of fluorescent probes to visualize processes such as endocytosis, intracellular transport or host cell manipulation by the pathogen. Here, three types of fluorescent nanoparticles (NPs), i.e. Rhodamine-labeled polymethacrylate (PMA) NPs, silica NPs and gold NPs, were employed to label the host cellular endolysosomal system and monitor manipulations by the pathogen Salmonella enterica. Using live cell imaging, we investigated the performance of NPs in cellular uptake, labeling of endocytic vesicles and lysosomes, as well as interaction with the pathogen. We show that fluorescent gold and silica, but not PMA NPs appropriately label host cell structures and efficiently track rearrangements of the host endosomal system by the activities of intracellular Salmonella. Silica NPs slightly aggregated and located in Salmonella-induced compartments as isolated dots, while gold NPs distributed uniformly inside such structures. Both silica and gold NPs exhibited no adverse impact on either host cells or pathogens, and are versatile tools for infection biology. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr01550e

X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus

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

Bornholdt, Zachary A.; Prasad, B.V. Venkataram

2009-04-08

The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains - a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker - is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60%more » of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-{angstrom}-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.« less

Host-Induced gene silencing in barley powdery mildew reveals a class of ribonuclease-like effectors

USDA-ARS?s Scientific Manuscript database

Obligate biotrophic pathogens of plants require the ability to circumvent host defenses to enable colonization. To establish compatibility, pathogens secrete a variety of effectors, which regulate host immunity, and thus, facilitate the establishment of haustorial feeding structures. These structur...

High-resolution transcript profiling of the atypical biotrophic interaction between Theobroma cacao and the fungal pathogen Moniliophthora perniciosa.

PubMed

Teixeira, Paulo José Pereira Lima; Thomazella, Daniela Paula de Toledo; Reis, Osvaldo; do Prado, Paula Favoretti Vital; do Rio, Maria Carolina Scatolin; Fiorin, Gabriel Lorencini; José, Juliana; Costa, Gustavo Gilson Lacerda; Negri, Victor Augusti; Mondego, Jorge Maurício Costa; Mieczkowski, Piotr; Pereira, Gonçalo Amarante Guimarães

2014-11-01

Witches' broom disease (WBD), caused by the hemibiotrophic fungus Moniliophthora perniciosa, is one of the most devastating diseases of Theobroma cacao, the chocolate tree. In contrast to other hemibiotrophic interactions, the WBD biotrophic stage lasts for months and is responsible for the most distinctive symptoms of the disease, which comprise drastic morphological changes in the infected shoots. Here, we used the dual RNA-seq approach to simultaneously assess the transcriptomes of cacao and M. perniciosa during their peculiar biotrophic interaction. Infection with M. perniciosa triggers massive metabolic reprogramming in the diseased tissues. Although apparently vigorous, the infected shoots are energetically expensive structures characterized by the induction of ineffective defense responses and by a clear carbon deprivation signature. Remarkably, the infection culminates in the establishment of a senescence process in the host, which signals the end of the WBD biotrophic stage. We analyzed the pathogen's transcriptome in unprecedented detail and thereby characterized the fungal nutritional and infection strategies during WBD and identified putative virulence effectors. Interestingly, M. perniciosa biotrophic mycelia develop as long-term parasites that orchestrate changes in plant metabolism to increase the availability of soluble nutrients before plant death. Collectively, our results provide unique insight into an intriguing tropical disease and advance our understanding of the development of (hemi)biotrophic plant-pathogen interactions. © 2014 American Society of Plant Biologists. All rights reserved.

Potential effects of mixed infections in ticks on transmission dynamics of pathogens: comparative analysis of published records

USGS Publications Warehouse

Ginsberg, Howard S.

2008-01-01

Ticks are often infected with more than one pathogen, and several field surveys have documented nonrandom levels of coinfection. Levels of coinfection by pathogens in four tick species were analyzed using published infection data. Coinfection patterns of pathogens in field-collected ticks include numerous cases of higher or lower levels of coinfection than would be expected due to chance alone, but the vast majority of these cases can be explained on the basis of vertebrate host associations of the pathogens, without invoking interactions between pathogens within ticks. Nevertheless, some studies have demonstrated antagonistic interactions, and some have suggested potential mutualisms, between pathogens in ticks. Negative or positive interactions between pathogens within ticks can affect pathogen prevalence, and thus transmission patterns. Probabilistic projections suggest that the effect on transmission depends on initial conditions. When the number of tick bites is relatively low (e.g., for ticks biting humans) changes in prevalence in ticks are predicted to have a commensurate effects on pathogen transmission. In contrast, when the number of tick bites is high (e.g., for wild animal hosts) changes in pathogen prevalence in ticks have relatively little effect on levels of transmission to reservoir hosts, and thus on natural transmission cycles.

Reconstructing the emergence of a lethal infectious disease of wildlife supports a key role for spread through translocations by humans

PubMed Central

Cunningham, Andrew A.; Langton, Tom E. S.

2016-01-01

There have been few reconstructions of wildlife disease emergences, despite their extensive impact on biodiversity and human health. This is in large part attributable to the lack of structured and robust spatio-temporal datasets. We overcame logistical problems of obtaining suitable information by using data from a citizen science project and formulating spatio-temporal models of the spread of a wildlife pathogen (genus Ranavirus, infecting amphibians). We evaluated three main hypotheses for the rapid increase in disease reports in the UK: that outbreaks were being reported more frequently, that climate change had altered the interaction between hosts and a previously widespread pathogen, and that disease was emerging due to spatial spread of a novel pathogen. Our analysis characterized localized spread from nearby ponds, consistent with amphibian dispersal, but also revealed a highly significant trend for elevated rates of additional outbreaks in localities with higher human population density—pointing to human activities in also spreading the virus. Phylogenetic analyses of pathogen genomes support the inference of at least two independent introductions into the UK. Together these results point strongly to humans repeatedly translocating ranaviruses into the UK from other countries and between UK ponds, and therefore suggest potential control measures. PMID:27683363

Vector-Borne Pathogen and Host Evolution in a Structured Immuno-Epidemiological System.

PubMed

Gulbudak, Hayriye; Cannataro, Vincent L; Tuncer, Necibe; Martcheva, Maia

2017-02-01

Vector-borne disease transmission is a common dissemination mode used by many pathogens to spread in a host population. Similar to directly transmitted diseases, the within-host interaction of a vector-borne pathogen and a host's immune system influences the pathogen's transmission potential between hosts via vectors. Yet there are few theoretical studies on virulence-transmission trade-offs and evolution in vector-borne pathogen-host systems. Here, we consider an immuno-epidemiological model that links the within-host dynamics to between-host circulation of a vector-borne disease. On the immunological scale, the model mimics antibody-pathogen dynamics for arbovirus diseases, such as Rift Valley fever and West Nile virus. The within-host dynamics govern transmission and host mortality and recovery in an age-since-infection structured host-vector-borne pathogen epidemic model. By considering multiple pathogen strains and multiple competing host populations differing in their within-host replication rate and immune response parameters, respectively, we derive evolutionary optimization principles for both pathogen and host. Invasion analysis shows that the [Formula: see text] maximization principle holds for the vector-borne pathogen. For the host, we prove that evolution favors minimizing case fatality ratio (CFR). These results are utilized to compute host and pathogen evolutionary trajectories and to determine how model parameters affect evolution outcomes. We find that increasing the vector inoculum size increases the pathogen [Formula: see text], but can either increase or decrease the pathogen virulence (the host CFR), suggesting that vector inoculum size can contribute to virulence of vector-borne diseases in distinct ways.

Unravelling Linkages between Plant Community Composition and the Pathogen-Suppressive Potential of Soils

PubMed Central

Latz, Ellen; Eisenhauer, Nico; Rall, Björn Christian; Scheu, Stefan; Jousset, Alexandre

2016-01-01

Plant diseases cause dramatic yield losses worldwide. Current disease control practices can be deleterious for the environment and human health, calling for alternative and sustainable management regimes. Soils harbour microorganisms that can efficiently suppress pathogens. Uncovering mediators driving their functioning in the field still remains challenging, but represents an essential step in order to develop strategies for increased soil health. We set up plant communities of varying richness to experimentally test the potential of soils differing in plant community history to suppress the pathogen Rhizoctonia solani. The results indicate that plant communities shape soil-disease suppression via changes in abiotic soil properties and the abundance of bacterial groups including species of the genera Actinomyces, Bacillus and Pseudomonas. Further, the results suggest that pairwise interactions between specific plant species strongly affect soil suppressiveness. Using structural equation modelling, we provide a pathway orientated framework showing how the complex interactions between plants, soil and microorganisms jointly shape soil suppressiveness. Our results stress the importance of plant community composition as a determinant of soil functioning, such as the disease suppressive potential of soils. PMID:27021053

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).

A plant natriuretic peptide-like gene in the bacterial pathogen Xanthomonas axonopodis may induce hyper-hydration in the plant host: a hypothesis of molecular mimicry.

PubMed

Nembaware, Victoria; Seoighe, Cathal; Sayed, Muhammed; Gehring, Chris

2004-03-24

Plant natriuretic peptides (PNPs) are systemically mobile molecules that regulate homeostasis at nanomolar concentrations. PNPs are up-regulated under conditions of osmotic stress and PNP-dependent processes include changes in ion transport and increases of H2O uptake into protoplasts and whole tissue. The bacterial citrus pathogen Xanthomonas axonopodis pv. Citri str. 306 contains a gene encoding a PNP-like protein. We hypothesise that this bacterial protein can alter plant cell homeostasis and thus is likely to represent an example of molecular mimicry that enables the pathogen to manipulate plant responses in order to bring about conditions favourable to the pathogen such as the induced plant tissue hyper-hydration seen in the wet edged lesions associated with Xanthomonas axonopodis infection. We found a Xanthomonas axonopodis PNP-like protein that shares significant sequence similarity and identical domain organisation with PNPs. We also observed a significant excess of conserved residues between the two proteins within the domain previously identified as being sufficient to induce biological activity. Structural modelling predicts identical six stranded double-psi beta barrel folds for both proteins thus supporting the hypothesis of similar modes of action. No significant similarity between the Xanthomonas axonopodis protein and other bacterial proteins from GenBank was found. Sequence similarity of the Xanthomonas axonopodis PNP-like protein with the Arabidopsis thaliana PNP (AtPNP-A), shared domain organisation and incongruent phylogeny suggest that the PNP-gene may have been acquired by the bacteria in an ancient lateral gene transfer event. Finally, activity of a recombinant Xanthomonas axonopodis protein in plant tissue and changes in symptoms induced by a Xanthomonas axonopodis mutant with a knocked-out PNP-like gene will be experimental proof of molecular mimicry. If the hypothesis is true, it could at least in part explain why the citrus pathogen Xanthomonas campestris that does not contain a PNP-like gene produces dry corky lesions while the closely related Xanthomonas axonopodis forms lesions with wet edges. It also suggests that genes typically found in the host, horizontally transferred or heterologous, can help to explain aspects of the physiology of the host-pathogen interactions.

Mapping of Proteomic Composition on the Surfaces of Bacillus spores by Atomic Force Microscopy-based Immunolabeling

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

Plomp, M; Malkin, A J

2008-06-02

Atomic force microscopy provides a unique capability to image high-resolution architecture and structural dynamics of pathogens (e.g. viruses, bacteria and bacterial spores) at near molecular resolution in native conditions. Further development of atomic force microscopy in order to enable the correlation of pathogen protein surface structures with specific gene products is essential to understand the mechanisms of the pathogen life cycle. We have applied an AFM-based immunolabeling technique for the proteomic mapping of macromolecular structures through the visualization of the binding of antibodies, conjugated with nanogold particles, to specific epitopes on Bacillus spore surfaces. This information is generated while simultaneouslymore » acquiring the surface morphology of the pathogen. The immunospecificity of this labeling method was established through the utilization of specific polyclonal and monoclonal antibodies that target spore coat and exosporium epitopes of Bacillus atrophaeus and Bacillus anthracis spores.« less

Methyl esterification of pectin plays a role during plant-pathogen interactions and affects plant resistance to diseases.

PubMed

Lionetti, Vincenzo; Cervone, Felice; Bellincampi, Daniela

2012-11-01

The cell wall is a complex structure mainly composed by a cellulose-hemicellulose network embedded in a cohesive pectin matrix. Pectin is synthesized in a highly methyl esterified form and is de-esterified in muro by pectin methyl esterases (PMEs). The degree and pattern of methyl esterification affect the cell wall structure and properties with consequences on both the physiological processes of the plants and their resistance to pathogens. PME activity displays a crucial role in the outcome of the plant-pathogen interactions by making pectin more susceptible to the action of the enzymes produced by the pathogens. This review focuses on the impact of pectin methyl esterification in plant-pathogen interactions and on the dynamic role of its alteration during pathogenesis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

DTIC Science & Technology

2003-01-01

epidemics, caused by Vibrio cholerae have been linked to specific seasons and biogeographical zones. In addition, the population dynamics of V. cholerae in...Climactic warming has directly affected the prevalence of RVFV by prolonging survival rates of the vector involved in disease transmission. 3 Cholera ...climate variability. The study of V. cholerae represents a model system of how climate change affects pathogens (2). Personal human behavior has

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

PubMed Central

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

2018-01-01

Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

A Review of Membrane-Based Biosensors for Pathogen Detection

PubMed Central

van den Hurk, Remko; Evoy, Stephane

2015-01-01

Biosensors are of increasing interest for the detection of bacterial pathogens in many applications such as human, animal and plant health, as well as food and water safety. Membranes and membrane-like structures have been integral part of several pathogen detection platforms. Such structures may serve as simple mechanical support, function as a part of the transduction mechanism, may be used to filter out or concentrate pathogens, and may be engineered to specifically house active proteins. This review focuses on membrane materials, their associated biosensing applications, chemical linking procedures, and transduction mechanisms. The sensitivity of membrane biosensors is discussed, and the state of the field is evaluated and summarized. PMID:26083229

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.

Structure of a Burkholderia pseudomallei Trimeric Autotransporter Adhesin Head

PubMed Central

Edwards, Thomas E.; Phan, Isabelle; Abendroth, Jan; Dieterich, Shellie H.; Masoudi, Amir; Guo, Wenjin; Hewitt, Stephen N.; Kelley, Angela; Leibly, David; Brittnacher, Mitch J.; Staker, Bart L.; Miller, Samuel I.; Van Voorhis, Wesley C.; Myler, Peter J.; Stewart, Lance J.

2010-01-01

Background Pathogenic bacteria adhere to the host cell surface using a family of outer membrane proteins called Trimeric Autotransporter Adhesins (TAAs). Although TAAs are highly divergent in sequence and domain structure, they are all conceptually comprised of a C-terminal membrane anchoring domain and an N-terminal passenger domain. Passenger domains consist of a secretion sequence, a head region that facilitates binding to the host cell surface, and a stalk region. Methodology/Principal Findings Pathogenic species of Burkholderia contain an overabundance of TAAs, some of which have been shown to elicit an immune response in the host. To understand the structural basis for host cell adhesion, we solved a 1.35 Å resolution crystal structure of a BpaA TAA head domain from Burkholderia pseudomallei, the pathogen that causes melioidosis. The structure reveals a novel fold of an intricately intertwined trimer. The BpaA head is composed of structural elements that have been observed in other TAA head structures as well as several elements of previously unknown structure predicted from low sequence homology between TAAs. These elements are typically up to 40 amino acids long and are not domains, but rather modular structural elements that may be duplicated or omitted through evolution, creating molecular diversity among TAAs. Conclusions/Significance The modular nature of BpaA, as demonstrated by its head domain crystal structure, and of TAAs in general provides insights into evolution of pathogen-host adhesion and may provide an avenue for diagnostics. PMID:20862217

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

PubMed Central

Peng, Yanhui; Loparev, Vladimir; Batra, Dhwani; Bowden, Katherine E.; Burroughs, Mark; Cassiday, Pamela K.; Davis, Jamie K.; Johnson, Taccara; Juieng, Phalasy; Knipe, Kristen; Mathis, Marsenia H.; Pruitt, Andrea M.; Rowe, Lori; Sheth, Mili; Tondella, M. Lucia; Williams, Margaret M.

2017-01-01

ABSTRACT Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. Although Bordetella pertussis is well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genomic structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257 B. pertussis isolates to examine the potential evolution of the chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. The observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS481, a mobile genetic element with >240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution in B. pertussis is not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigating disease resurgence and molecular epidemiology. IMPORTANCE Whooping cough, primarily caused by Bordetella pertussis, has resurged in the United States even though the coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome of B. pertussis includes a large number of repetitive mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-encoding genes, which otherwise exhibit little nucleotide sequence diversity. By comparing the complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology. PMID:28167525

Climate-induced behavioral changes influence exposure of an Arctic apex predator to pathogens and contaminants

USDA-ARS?s Scientific Manuscript database

Polar bears (Ursus maritimus) may serve as sentinels for pathogens and contaminants, providing insight into changing Arctic ecosystems and health risks to wildlife and humans. Recent changes in the availability of sea ice habitat have coincided with increased use of land by polar bears from the sout...

Ecology of zoonotic infectious diseases in bats: current knowledge and future directions

USGS Publications Warehouse

Hayman, D.T.; Bowen, R.A.; Cryan, P.M.; McCracken, G.F.; O'Shea, T.J.; Peel, A.J.; Gilbert, A.; Webb, C.T.; Wood, J.L.

2013-01-01

Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data-driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics.

Ecology of Zoonotic Infectious Diseases in Bats: Current Knowledge and Future Directions

PubMed Central

Hayman, D T S; Bowen, R A; Cryan, P M; McCracken, G F; O’Shea, T J; Peel, A J; Gilbert, A; Webb, C T; Wood, J L N

2013-01-01

Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data-driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics. PMID:22958281

In Vivo Study of Trichoderma-Pathogen-Plant Interactions, Using Constitutive and Inducible Green Fluorescent Protein Reporter Systems

PubMed Central

Lu, Zexun; Tombolini, Riccardo; Woo, Sheridan; Zeilinger, Susanne; Lorito, Matteo; Jansson, Janet K.

2004-01-01

Plant tissue colonization by Trichoderma atroviride plays a critical role in the reduction of diseases caused by phytopathogenic fungi, but this process has not been thoroughly studied in situ. We monitored in situ interactions between gfp-tagged biocontrol strains of T. atroviride and soilborne plant pathogens that were grown in cocultures and on cucumber seeds by confocal scanning laser microscopy and fluorescence stereomicroscopy. Spores of T. atroviride adhered to Pythium ultimum mycelia in coculture experiments. In mycoparasitic interactions of T. atroviride with P. ultimum or Rhizoctonia solani, the mycoparasitic hyphae grew alongside the pathogen mycelia, and this was followed by coiling and formation of specialized structures similar to hooks, appressoria, and papillae. The morphological changes observed depended on the pathogen tested. Branching of T. atroviride mycelium appeared to be an active response to the presence of the pathogenic host. Mycoparasitism of P. ultimum by T. atroviride occurred on cucumber seed surfaces while the seeds were germinating. The interaction of these fungi on the cucumber seeds was similar to the interaction observed in coculture experiments. Green fluorescent protein expression under the control of host-inducible promoters was also studied. The induction of specific Trichoderma genes was monitored visually in cocultures, on plant surfaces, and in soil in the presence of colloidal chitin or Rhizoctonia by confocal microscopy and fluorescence stereomicroscopy. These tools allowed initiation of the mycoparasitic gene expression cascade to be monitored in vivo. PMID:15128569

Fungal Infection Induces Sex-Specific Transcriptional Changes and Alters Sexual Dimorphism in the Dioecious Plant Silene latifolia

PubMed Central

Zemp, Niklaus; Tavares, Raquel; Widmer, Alex

2015-01-01

Sexual dimorphism, including differences in morphology, behavior and physiology between females and males, is widespread in animals and plants and is shaped by gene expression differences between the sexes. Such expression differences may also underlie sex-specific responses of hosts to pathogen infections, most notably when pathogens induce partial sex reversal in infected hosts. The genetic changes associated with sex-specific responses to pathogen infections on the one hand, and sexual dimorphism on the other hand, remain poorly understood. The dioecious White Campion (Silene latifolia) displays sexual dimorphism in floral traits and infection with the smut fungus Micobrotryum lychnidis-dioicae induces a partial sex reversal in females. We find strong sex-specific responses to pathogen infection and reduced sexual dimorphism in infected S. latifolia. This provides a direct link between pathogen-mediated changes in sex-biased gene expression and altered sexual dimorphism in the host. Expression changes following infection affected mainly genes with male-biased expression in healthy plants. In females, these genes were up-regulated, leading to a masculinization of the transcriptome. In contrast, infection in males was associated with down-regulation of these genes, leading to a demasculinization of the transcriptome. To a lesser extent, genes with female-biased expression in healthy plants were also affected in opposite directions in the two sexes. These genes were overall down-regulated in females and up-regulated in males, causing, respectively, a defeminization in infected females and a feminization of the transcriptome in infected males. Our results reveal strong sex-specific responses to pathogen infection in a dioecious plant and provide a link between pathogen-induced changes in sex-biased gene expression and sexual dimorphism. PMID:26448481

Fungal Infection Induces Sex-Specific Transcriptional Changes and Alters Sexual Dimorphism in the Dioecious Plant Silene latifolia.

PubMed

Zemp, Niklaus; Tavares, Raquel; Widmer, Alex

2015-10-01

Sexual dimorphism, including differences in morphology, behavior and physiology between females and males, is widespread in animals and plants and is shaped by gene expression differences between the sexes. Such expression differences may also underlie sex-specific responses of hosts to pathogen infections, most notably when pathogens induce partial sex reversal in infected hosts. The genetic changes associated with sex-specific responses to pathogen infections on the one hand, and sexual dimorphism on the other hand, remain poorly understood. The dioecious White Campion (Silene latifolia) displays sexual dimorphism in floral traits and infection with the smut fungus Micobrotryum lychnidis-dioicae induces a partial sex reversal in females. We find strong sex-specific responses to pathogen infection and reduced sexual dimorphism in infected S. latifolia. This provides a direct link between pathogen-mediated changes in sex-biased gene expression and altered sexual dimorphism in the host. Expression changes following infection affected mainly genes with male-biased expression in healthy plants. In females, these genes were up-regulated, leading to a masculinization of the transcriptome. In contrast, infection in males was associated with down-regulation of these genes, leading to a demasculinization of the transcriptome. To a lesser extent, genes with female-biased expression in healthy plants were also affected in opposite directions in the two sexes. These genes were overall down-regulated in females and up-regulated in males, causing, respectively, a defeminization in infected females and a feminization of the transcriptome in infected males. Our results reveal strong sex-specific responses to pathogen infection in a dioecious plant and provide a link between pathogen-induced changes in sex-biased gene expression and sexual dimorphism.

The antibiotic activity and mechanisms of sugarcane (Saccharum officinarum L.) bagasse extract against food-borne pathogens.

PubMed

Zhao, Yi; Chen, Mingshun; Zhao, Zhengang; Yu, Shujuan

2015-10-15

Sugarcane bagasse contains natural compositions that can significantly inhibit food-borne pathogens growth. In the present study, the phenolic content in sugarcane bagasse was detected as higher than 4 mg/g dry bagasse, with 470 mg quercetin/g polyphenol. The sugarcane bagasse extract showed bacteriostatic activity against the growth of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salomonella typhimurium. Additionally, the sugarcane bagasse extract can increase the electric conductivity of bacterial cell suspensions causing cellular leaking of electrolytes. Results of sodium dodecyl sulfate polyacrylamide gel electrophoresis suggested the antibacterial mechanism was probably due to the damaged cellular proteins by sugarcane bagasse extract. The results of scanning electron microscopy and transmission electron microscopy showed that the sugarcane bagasse extract might change cell morphology and internal structure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alterations in Hemagglutinin Receptor-Binding Specificity Accompany the Emergence of Highly Pathogenic Avian Influenza Viruses

PubMed Central

Mochalova, Larisa; Harder, Timm; Tuzikov, Alexander; Bovin, Nicolai; Wolff, Thorsten; Matrosovich, Mikhail; Schweiger, Brunhilde

2015-01-01

ABSTRACT Highly pathogenic avian influenza viruses (HPAIVs) of hemagglutinin H5 and H7 subtypes emerge after introduction of low-pathogenic avian influenza viruses (LPAIVs) from wild birds into poultry flocks, followed by subsequent circulation and evolution. The acquisition of multiple basic amino acids at the endoproteolytical cleavage site of the hemagglutinin (HA) is a molecular indicator for high pathogenicity, at least for infections of gallinaceous poultry. Apart from the well-studied significance of the multibasic HA cleavage site, there is only limited knowledge on other alterations in the HA and neuraminidase (NA) molecules associated with changes in tropism during the emergence of HPAIVs from LPAIVs. We hypothesized that changes in tropism may require alterations of the sialyloligosaccharide specificities of HA and NA. To test this hypothesis, we compared a number of LPAIVs and HPAIVs for their HA-mediated binding and NA-mediated desialylation of a set of synthetic receptor analogs, namely, α2-3-sialylated oligosaccharides. NA substrate specificity correlated with structural groups of NAs and did not correlate with pathogenic potential of the virus. In contrast, all HPAIVs differed from LPAIVs by a higher HA receptor-binding affinity toward the trisaccharides Neu5Acα2-3Galβ1-4GlcNAcβ (3′SLN) and Neu5Acα2-3Galβ1-3GlcNAcβ (SiaLec) and by the ability to discriminate between the nonfucosylated and fucosylated sialyloligosaccharides 3′SLN and Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ (SiaLex), respectively. These results suggest that alteration of the receptor-binding specificity accompanies emergence of the HPAIVs from their low-pathogenic precursors. IMPORTANCE Here, we have found for the first time correlations of receptor-binding properties of the HA with a highly pathogenic phenotype of poultry viruses. Our study suggests that enhanced receptor-binding affinity of HPAIVs for a typical “poultry-like” receptor, 3′SLN, is provided by substitutions in the receptor-binding site of HA which appeared in HA of LPAIVs in the course of transmission of LPAIVs from wild waterfowl into poultry flocks, with subsequent adaptation in poultry. The identification of LPAIVs with receptor characteristics of HPAIVs argues that the sialic acid-binding specificity of the HA may be used as a novel phenotypic marker of HPAIVs. PMID:25741006

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

Direct and indirect effects of climate change on amphibian populations

USGS Publications Warehouse

Blaustein, Andrew R.; Walls, Susan C.; Bancroft, Betsy A.; Lawler, Joshua J.; Searle, Catherine L.; Gervasi, Stephanie S.

2010-01-01

As part of an overall decline in biodiversity, populations of many organisms are declining and species are being lost at unprecedented rates around the world. This includes many populations and species of amphibians. Although numerous factors are affecting amphibian populations, we show potential direct and indirect effects of climate change on amphibians at the individual, population and community level. Shifts in amphibian ranges are predicted. Changes in climate may affect survival, growth, reproduction and dispersal capabilities. Moreover, climate change can alter amphibian habitats including vegetation, soil, and hydrology. Climate change can influence food availability, predator-prey relationships and competitive interactions which can alter community structure. Climate change can also alter pathogen-host dynamics and greatly influence how diseases are manifested. Changes in climate can interact with other stressors such as UV-B radiation and contaminants. The interactions among all these factors are complex and are probably driving some amphibian population declines and extinctions.

Arabidopsis histone methyltransferase SET DOMAIN GROUP8 mediates induction of the jasmonate/ethylene pathway genes in plant defense response to necrotrophic fungi.

PubMed

Berr, Alexandre; McCallum, Emily J; Alioua, Abdelmalek; Heintz, Dimitri; Heitz, Thierry; Shen, Wen-Hui

2010-11-01

As sessile organisms, plants have to endure a wide variety of biotic and abiotic stresses, and accordingly they have evolved intricate and rapidly inducible defense strategies associated with the activation of a battery of genes. Among other mechanisms, changes in chromatin structure are thought to provide a flexible, global, and stable means for the regulation of gene transcription. In support of this idea, we demonstrate here that the Arabidopsis (Arabidopsis thaliana) histone methyltransferase SET DOMAIN GROUP8 (SDG8) plays a crucial role in plant defense against fungal pathogens by regulating a subset of genes within the jasmonic acid (JA) and/or ethylene signaling pathway. We show that the loss-of-function mutant sdg8-1 displays reduced resistance to the necrotrophic fungal pathogens Alternaria brassicicola and Botrytis cinerea. While levels of JA, a primary phytohormone involved in plant defense, and camalexin, a major phytoalexin against fungal pathogens, remain unchanged or even above normal in sdg8-1, induction of several defense genes within the JA/ethylene signaling pathway is severely compromised in response to fungal infection or JA treatment in mutant plants. Both downstream genes and, remarkably, also upstream mitogen-activated protein kinase kinase genes MKK3 and MKK5 are misregulated in sdg8-1. Accordingly, chromatin immunoprecipitation analysis shows that sdg8-1 impairs dynamic changes of histone H3 lysine 36 methylation at defense marker genes as well as at MKK3 and MKK5, which normally occurs upon infection with fungal pathogens or methyl JA treatment in wild-type plants. Our data indicate that SDG8-mediated histone H3 lysine 36 methylation may serve as a memory of permissive transcription for a subset of defense genes, allowing rapid establishment of transcriptional induction.

Antimicrobial Effects of 7,8-Dihydroxy-6-Methoxycoumarin and 7-Hydroxy-6-Methoxycoumarin Analogues against Foodborne Pathogens and the Antimicrobial Mechanisms Associated with Membrane Permeability.

PubMed

Yang, Ji-Yeon; Park, Jun-Hwan; Lee, Myung-Ji; Lee, Ji-Hoon; Lee, Hoi-Seon

2017-10-03

The antimicrobial effects of 7,8-dihydroxy-6-methoxycoumarin and 7-hydroxy-6-methoxycoumarin isolated from Fraxinus rhynchophylla bark and of their structural analogues were determined in an attempt to develop natural antimicrobial agents against the foodborne pathogens Escherichia coli, Bacillus cereus, Staphylococcus intermedius, and Listeria monocytogenes. To elucidate the relationship between structure and antimicrobial activity for the coumarin analogues, isolated constituents and their structural analogues were evaluated against foodborne pathogens. Based on the culture plate inhibition zones and MICs, 6,7-dimethoxycoumarin, 7,8-dihydroxy-6-methoxycoumarin, 7-hydroxy-6-methoxycoumarin, and 7-methoxycoumarin, containing a methoxy functional group on the coumarin skeleton, had the notable antimicrobial activity against foodborne pathogens. However, 7-hydroxycoumarin and 6,7-dihydroxycoumarin, which contained a hydroxyl functional group on the coumarin skeleton, had no antimicrobial activity against these pathogens. An increase in cell membrane permeability was confirmed by electron microscopy observations, and release of extracellular ATP and cell constituents followed treatment with the ethyl acetate fraction of F. rhynchophylla extract. These findings indicate that F. rhynchophylla extract and coumarin analogues have potential for use as antimicrobial agents against foodborne pathogens and that the antimicrobial mechanisms are associated with the loss of cell membrane integrity.

TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis

PubMed Central

Guerreiro, Rita J.; Schymick, Jennifer C.; Crews, Cynthia; Singleton, Andrew; Hardy, John; Traynor, Bryan J.

2008-01-01

Background TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. Methodology/Principal Findings To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus. Conclusions Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American. PMID:18545701

[Biological preparations with different mechanism of action for protecting potato against fungal diseases].

PubMed

Kulikov, S N; Alimova, F K; Zakharova, N G; Nemtsev, S V; Varlamov, V P

2006-01-01

Mycological analysis throughout the vegetation period of potato (Solanum tuberosum) made it possible to study in detail the structure of micromycete community, to determine typical dominant (frequency, more than 60%), typical common (frequency, 30 to 60%), typical rare (frequency, 10 to 30%), and casual (frequency, less than 10%) species and to estimate changes in the microorganism community caused by plant protection preparations with different mechanisms of action. It was shown that, as a result of occurrence of resistant forms, synthetic preparations against fungal pathogens of potato (such as TMTD, Ridomil gold MC, and Cupricol) were only slightly more effective than biological preparations (Trichodermin and AgroChit), with the former considerably changing the natural saprophytic mycological community. An increase in the soil pool of Trichoderma harzianum as a result of application of a biological preparation based on this antagonistic fungus correlated with its effectiveness against the soil pathogen Fusarium sp., which causes root rots. A chitosan-based elicitor preparation more effectively suppressed the development of early (Alternaria sp. and Macrosporium sp.) and late (Phytophthora sp.) blights of leaves and had a weaker effect on the soil microflora.

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.

Autophagy in plant pathogenic fungi.

PubMed

Liu, Xiao-Hong; Xu, Fei; Snyder, John Hugh; Shi, Huan-Bin; Lu, Jian-Ping; Lin, Fu-Cheng

2016-09-01

Autophagy is a conserved cellular process that degrades cytoplasmic constituents in vacuoles. Plant pathogenic fungi develop special infection structures and/or secrete a range of enzymes to invade their plant hosts. It has been demonstrated that monitoring autophagy processes can be extremely useful in visualizing the sequence of events leading to pathogenicity of plant pathogenic fungi. In this review, we introduce the molecular mechanisms involved in autophagy. In addition, we explore the relationship between autophagy and pathogenicity in plant pathogenic fungi. Finally, we discuss the various experimental strategies available for use in the study of autophagy in plant pathogenic fungi. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changing Epidemiology of the Respiratory Bacteriology of Patients With Cystic Fibrosis.

PubMed

Salsgiver, Elizabeth L; Fink, Aliza K; Knapp, Emily A; LiPuma, John J; Olivier, Kenneth N; Marshall, Bruce C; Saiman, Lisa

2016-02-01

Monitoring potential changes in the epidemiology of cystic fibrosis (CF) pathogens furthers our understanding of the potential impact of interventions. We performed a retrospective analysis using data reported to the Cystic Fibrosis Foundation Patient Registry (CFFPR) from 2006 to 2012 to determine the annual percent changes in the prevalence and incidence of selected CF pathogens. Pathogens included Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), Haemophilus influenzae, Burkholderia cepacia complex, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. Changes in nontuberculous mycobacteria (NTM) prevalence were assessed from 2010 to 2012, when the CFFPR collected NTM species. In 2012, the pathogens of highest prevalence and incidence were MSSA and P aeruginosa, followed by MRSA. The prevalence of A xylosoxidans and B cepacia complex were relatively low. From 2006 to 2012, the annual percent change in overall (as well as in most age strata) prevalence and incidence significantly decreased for P aeruginosa and B cepacia complex, but significantly increased for MRSA. From 2010 to 2012, the annual percent change in overall prevalence of NTM and Mycobaterium avium complex increased. The epidemiology of CF pathogens continues to change. The causes of these observations are most likely multifactorial and include improvements in clinical care and infection prevention and control. Data from this study will be useful to evaluate the impact of new therapies on CF microbiology. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Atypical face shape and genomic structural variants in epilepsy

PubMed Central

Chinthapalli, Krishna; Bartolini, Emanuele; Novy, Jan; Suttie, Michael; Marini, Carla; Falchi, Melania; Fox, Zoe; Clayton, Lisa M. S.; Sander, Josemir W.; Guerrini, Renzo; Depondt, Chantal; Hennekam, Raoul; Hammond, Peter

2012-01-01

Many pathogenic structural variants of the human genome are known to cause facial dysmorphism. During the past decade, pathogenic structural variants have also been found to be an important class of genetic risk factor for epilepsy. In other fields, face shape has been assessed objectively using 3D stereophotogrammetry and dense surface models. We hypothesized that computer-based analysis of 3D face images would detect subtle facial abnormality in people with epilepsy who carry pathogenic structural variants as determined by chromosome microarray. In 118 children and adults attending three European epilepsy clinics, we used an objective measure called Face Shape Difference to show that those with pathogenic structural variants have a significantly more atypical face shape than those without such variants. This is true when analysing the whole face, or the periorbital region or the perinasal region alone. We then tested the predictive accuracy of our measure in a second group of 63 patients. Using a minimum threshold to detect face shape abnormalities with pathogenic structural variants, we found high sensitivity (4/5, 80% for whole face; 3/5, 60% for periorbital and perinasal regions) and specificity (45/58, 78% for whole face and perinasal regions; 40/58, 69% for periorbital region). We show that the results do not seem to be affected by facial injury, facial expression, intellectual disability, drug history or demographic differences. Finally, we use bioinformatics tools to explore relationships between facial shape and gene expression within the developing forebrain. Stereophotogrammetry and dense surface models are powerful, objective, non-contact methods of detecting relevant face shape abnormalities. We demonstrate that they are useful in identifying atypical face shape in adults or children with structural variants, and they may give insights into the molecular genetics of facial development. PMID:22975390

Phytophthora community structure analyses in Oregon nurseries inform systems approaches to disease management

Treesearch

J.L. Parke; B.J. Knaus; V.J. Fieland; C. Lewis; N.J. Grünwald

2014-01-01

Nursery plants are important vectors for plant pathogens. Understanding what pathogens occur in nurseries in different production stages can be useful to the development of integrated systems approaches. Four horticultural nurseries in Oregon were sampled every 2 months for 4 years to determine the identity and community structure of Phytophthora...

Fiber Diffraction of the Prion-Forming Domain HET-s(218-289) Shows Dehydration-Induced Deformation of a Complex Amyloid Structure

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

Wan, William; Stubbs, Gerald

2014-05-01

Amyloids are filamentous protein aggregates that can be formed by many different proteins and are associated with both disease and biological functions. The pathogenicities or biological functions of amyloids are determined by their particular molecular structures, making accurate structural models a requirement for understanding their biological effects. One potential factor that can affect amyloid structures is hydration. Previous studies of simple stacked β-sheet amyloids have suggested that dehydration does not impact structure, but other studies indicated dehydration-related structural changes of a putative water-filled nanotube. Our results show that dehydration significantly affects the molecular structure of the fungal prion-forming domain HET-s(218–289),more » which forms a β-solenoid with no internal solvent-accessible regions. The dehydration-related structural deformation of HET-s(218–289) indicates that water can play a significant role in complex amyloid structures, even when no obvious water-accessible cavities are present.« less

Discovery of an ultra-short linear antibacterial tetrapeptide with anti-MRSA activity from a structure-activity relationship study.

PubMed

Lau, Qiu Ying; Ng, Fui Mee; Cheong, Jin Wei Darryl; Yap, Yi Yong Alvin; Tan, Yoke Yan Fion; Jureen, Roland; Hill, Jeffrey; Chia, Cheng San Brian

2015-11-13

The overuse and misuse of antibiotics has resulted in the emergence of drug-resistant pathogenic bacteria, including meticillin-resistant Staphylococcus aureus (MRSA), the primary pathogen responsible for human skin and soft-tissue infections. Antibacterial peptides are known to kill bacteria by rapidly disrupting their membranes and are deemed plausible alternatives to conventional antibiotics. One advantage of their membrane-targeting mode of action is that bacteria are unlikely to develop resistance as changing their cell membrane structure and morphology would likely involve extensive genetic mutations. However, major concerns in using peptides as antibacterial drugs include their instability towards plasma proteases, toxicity towards human cells due to their membrane-targeting mode of action and high manufacturing cost. These concerns can be mitigated by developing peptides as topical agents, by the judicial selection of amino acids and developing very short peptides respectively. In this preliminary report, we reveal a linear, non-hemolytic tetrapeptide with rapid bactericidal activity against MRSA developed from a structure-activity relationship study based on the antimicrobial hexapeptide WRWRWR-NH2. Our finding opens promising avenues for the development of ultra-short antibacterials to treat multidrug-resistant MRSA skin and soft tissue infections. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe–host interactions

PubMed Central

Sequeira, Saannya; Kavanaugh, Devon; MacKenzie, Donald A.; Walpole, Samuel; Leclaire, Charlotte; Gunning, A. Patrick; Latousakis, Dimitrios; Willats, William G. T.; Dong, Changjiang; Juge, Nathalie

2018-01-01

Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens, but no structural information is available in commensal bacteria. Here we report the 2.00-Å and 1.92-Å crystal structures of the binding regions (BRs) of SRRP100-23 and SRRP53608 from L. reuteri ATCC 53608, revealing a unique β-solenoid fold in this important adhesin family. SRRP53608-BR bound to host epithelial cells and DNA at neutral pH and recognized polygalacturonic acid (PGA), rhamnogalacturonan I, or chondroitin sulfate A at acidic pH. Mutagenesis confirmed the role of the BR putative binding site in the interaction of SRRP53608-BR with PGA. Long molecular dynamics simulations showed that SRRP53608-BR undergoes a pH-dependent conformational change. Together, these findings provide mechanistic insights into the role of SRRPs in host–microbe interactions and open avenues of research into the use of biofilm-forming probiotics against clinically important pathogens. PMID:29507249

Molecular assessment of bacterial pathogens - a contribution to drinking water safety.

PubMed

Brettar, Ingrid; Höfle, Manfred G

2008-06-01

Human bacterial pathogens are considered as an increasing threat to drinking water supplies worldwide because of the growing demand of high-quality drinking water and the decreasing quality and quantity of available raw water. Moreover, a negative impact of climate change on freshwater resources is expected. Recent advances in molecular detection technologies for bacterial pathogens in drinking water bear the promise in improving the safety of drinking water supplies by precise detection and identification of the pathogens. More importantly, the array of molecular approaches allows understanding details of infection routes of waterborne diseases, the effects of changes in drinking water treatment, and management of freshwater resources.

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.

Daphnia magna shows reduced infection upon secondary exposure to a pathogen

PubMed Central

McTaggart, Seanna J.; Wilson, Philip J.; Little, Tom J.

2012-01-01

Previous pathogen exposure is an important predictor of the probability of becoming infected. This is deeply understood for vertebrate hosts, and increasingly so for invertebrate hosts. Here, we test if an initial pathogen exposure changes the infection outcome to a secondary pathogen exposure in the natural host–pathogen system Daphnia magna and Pasteuria ramosa. Hosts were initially exposed to an infective pathogen strain, a non-infective pathogen strain or a control. The same hosts underwent a second exposure, this time to an infective pathogen strain, either immediately after the initial encounter or 48 h later. We observed that an initial encounter with a pathogen always conferred protection against infection compared with controls. PMID:22875818

Daphnia magna shows reduced infection upon secondary exposure to a pathogen.

PubMed

McTaggart, Seanna J; Wilson, Philip J; Little, Tom J

2012-12-23

Previous pathogen exposure is an important predictor of the probability of becoming infected. This is deeply understood for vertebrate hosts, and increasingly so for invertebrate hosts. Here, we test if an initial pathogen exposure changes the infection outcome to a secondary pathogen exposure in the natural host-pathogen system Daphnia magna and Pasteuria ramosa. Hosts were initially exposed to an infective pathogen strain, a non-infective pathogen strain or a control. The same hosts underwent a second exposure, this time to an infective pathogen strain, either immediately after the initial encounter or 48 h later. We observed that an initial encounter with a pathogen always conferred protection against infection compared with controls.

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.

Comparative population genomics of Fusarium graminearum reveals adaptive divergence among cereal head blight pathogens

USDA-ARS?s Scientific Manuscript database

In this study we sequenced the genomes of 60 Fusarium graminearum, the major fungal pathogen responsible for Fusarium head blight (FHB) in cereal crops world-wide. To investigate adaptive evolution of FHB pathogens, we performed population-level analyses to characterize genomic structure, signatures...

Global genetic structure of the fungal grapevine pathogen Eutypa lata

USDA-ARS?s Scientific Manuscript database

The ascomycete fungus Eutypa lata is a trunk pathogen of cultivated grapevine (Vitis vinifera) in all major grape-growing regions of the world. Throughout its geographic range, it is considered a generalist pathogen that can complete its life cycle on a broad range of hosts. To decipher the cosmopol...

Changes in structure and function of fungal community in cow manure composting.

PubMed

Wang, Ke; Yin, Xiangbo; Mao, Hailong; Chu, Chu; Tian, Yu

2018-05-01

In this study, dynamic changes in fungal communities, trophic modes and effect factors in 60 days composting of cow manure were analyzed by using high throughput sequencing, FUNGuild and Biolog FF MicroPlate, respectively. Orpinomyces (relative abundance >10.85%) predominated in feedstock, and Mycothermus became the dominating genus (relative abundance >75%) during the active phase. Aerobic composting treatment had a significant effect on fungal trophic modes with pathogenic fungi fading away and wood saprotrophs increasing over composting time. Fungal communities had the higher carbon sources utilization capabilities at the thermophilic phase and mature phase than those in the other periods. Oxidation reduction potential (ORP) significantly increased from -180 to 180 mV during the treatment. Redundancy analysis showed that the succession of fungal community during composting had a significant association with ORP (p < .05). This indicated that aerobic composting treatment not only influenced fungal community structure, but also changed fungal trophic modes and metabolic characteristics. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Relationship between the Structure of the Tick-Borne Encephalitis Virus Strains and Their Pathogenic Properties

PubMed Central

Belikov, Sergei I.; Kondratov, Ilya G.; Potapova, Ulyana V.; Leonova, Galina N.

2014-01-01

Tick-borne encephalitis virus (TBEV) is transmitted to vertebrates by taiga or forest ticks through bites, inducing disease of variable severity. The reasons underlying these differences in the severity of the disease are unknown. In order to identify genetic factors affecting the pathogenicity of virus strains, we have sequenced and compared the complete genomes of 34 Far-Eastern subtype (FE) TBEV strains isolated from patients with different disease severity (Primorye, the Russian Far East). We analyzed the complete genomes of 11 human pathogenic strains isolated from the brains of dead patients with the encephalitic form of the disease (Efd), 4 strains from the blood of patients with the febrile form of TBE (Ffd), and 19 strains from patients with the subclinical form of TBE (Sfd). On the phylogenetic tree, pathogenic Efd strains formed two clusters containing the prototype strains, Senzhang and Sofjin, respectively. Sfd strains formed a third separate cluster, including the Oshima strain. The strains that caused the febrile form of the disease did not form a separate cluster. In the viral proteins, we found 198 positions with at least one amino acid residue substitution, of which only 17 amino acid residue substitutions were correlated with the variable pathogenicity of these strains in humans and they authentically differed between the groups. We considered the role of each amino acid substitution and assumed that the deletion of 111 amino acids in the capsid protein in combination with the amino acid substitutions R16K and S45F in the NS3 protease may affect the budding process of viral particles. These changes may be the major reason for the diminished pathogenicity of TBEV strains. We recommend Sfd strains for testing as attenuation vaccine candidates. PMID:24740396

Molecular Epidemiology and Genetic Variation of Pathogenic Vibrio parahaemolyticus in Peru

PubMed Central

Gavilan, Ronnie G.; Zamudio, Maria L.; Martinez-Urtaza, Jaime

2013-01-01

Vibrio parahaemolyticus is a foodborne pathogen that has become a public health concern at the global scale. The epidemiological significance of V. parahaemolyticus infections in Latin America received little attention until the winter of 1997 when cases related to the pandemic clone were detected in the region, changing the epidemic dynamics of this pathogen in Peru. With the aim to assess the impact of the arrival of the pandemic clone on local populations of pathogenic V. parahaemolyticus in Peru, we investigated the population genetics and genomic variation in a complete collection of non-pandemic strains recovered from clinical sources in Peru during the pre- and post-emergence periods of the pandemic clone. A total of 56 clinical strains isolated in Peru during the period 1994 to 2007, 13 strains from Chile and 20 strains from Asia were characterized by Multilocus Sequence Typing (MLST) and checked for the presence of Variable Genomic Regions (VGRs). The emergence of O3:K6 cases in Peru implied a drastic disruption of the seasonal dynamics of infections and a shift in the serotype dominance of pathogenic V. parahaemolyticus. After the arrival of the pandemic clone, a great diversity of serovars not previously reported was detected in the country, which supports the introduction of additional populations cohabitating with the pandemic group. Moreover, the presence of genomic regions characteristic of the pandemic clone in other non-pandemic strains may represent early evidence of genetic transfer from the introduced population to the local communities. Finally, the results of this study stress the importance of population admixture, horizontal genetic transfer and homologous recombination as major events shaping the structure and diversity of pathogenic V. parahaemolyticus. PMID:23696906

The Crystal Structures of Apo and cAMP-Bound GlxR from Corynebacterium glutamicum Reveal Structural and Dynamic Changes upon cAMP Binding in CRP/FNR Family Transcription Factors

PubMed Central

Townsend, Philip D.; Jungwirth, Britta; Pojer, Florence; Bußmann, Michael; Money, Victoria A.; Cole, Stewart T.; Pühler, Alfred; Tauch, Andreas; Bott, Michael; Cann, Martin J.; Pohl, Ehmke

2014-01-01

The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition. PMID:25469635

Evolution of acuteness in pathogen metapopulations: conflicts between “classical” and invasion-persistence trade-offs

PubMed Central

Shrestha, Sourya; Bjørnstad, Ottar N.; King, Aaron A.

2014-01-01

Classical life-history theory predicts that acute, immunizing pathogens should maximize between-host transmission. When such pathogens induce violent epidemic outbreaks, however, a pathogen’s short-term advantage at invasion may come at the expense of its ability to persist in the population over the long term. Here, we seek to understand how the classical and invasion-persistence trade-offs interact to shape pathogen life-history evolution as a function of the size and structure of the host population. We develop an individual-based infection model at three distinct levels of organization: within an individual host, among hosts within a local population, and among local populations within a metapopulation. We find a continuum of evolutionarily stable pathogen strategies. At one end of the spectrum—in large well-mixed populations—pathogens evolve to greater acuteness to maximize between-host transmission: the classical trade-off theory applies in this regime. At the other end of the spectrum—when the host population is broken into many small patches—selection favors less acute pathogens, which persist longer within a patch and thereby achieve enhanced between-patch transmission: the invasion-persistence tradeoff dominates in this regime. Between these extremes, we explore the effects of the size and structure of the host population in determining pathogen strategy. In general, pathogen strategies respond to evolutionary pressures arising at both scales. PMID:25214895

Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels.

PubMed

Arnold, Benjamin F; van der Laan, Mark J; Hubbard, Alan E; Steel, Cathy; Kubofcik, Joseph; Hamlin, Katy L; Moss, Delynn M; Nutman, Thomas B; Priest, Jeffrey W; Lammie, Patrick J

2017-05-01

Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays. We developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearman's rho = 0.75). In both high- and low transmission settings, mean antibody curves revealed changes in population mean antibody levels that were masked by seroprevalence measures because changes took place above or below the seropositivity cutoff. Age-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, and scales to surveillance activities that require high spatiotemporal resolution. Our results suggest quantitative antibody levels will be particularly useful to measure differences in exposure for pathogens that elicit a transient antibody response or for monitoring populations with very high- or very low transmission, when seroprevalence is less informative. The approach represents a new opportunity to conduct integrated serological surveillance for neglected tropical diseases, malaria, and other infectious diseases with well-defined antigen targets.

Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels

PubMed Central

van der Laan, Mark J.; Hubbard, Alan E.; Steel, Cathy; Kubofcik, Joseph; Hamlin, Katy L.; Moss, Delynn M.; Nutman, Thomas B.; Priest, Jeffrey W.; Lammie, Patrick J.

2017-01-01

Background Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays. Methods/Principal findings We developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearman’s rho = 0.75). In both high- and low transmission settings, mean antibody curves revealed changes in population mean antibody levels that were masked by seroprevalence measures because changes took place above or below the seropositivity cutoff. Conclusions/Significance Age-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, and scales to surveillance activities that require high spatiotemporal resolution. Our results suggest quantitative antibody levels will be particularly useful to measure differences in exposure for pathogens that elicit a transient antibody response or for monitoring populations with very high- or very low transmission, when seroprevalence is less informative. The approach represents a new opportunity to conduct integrated serological surveillance for neglected tropical diseases, malaria, and other infectious diseases with well-defined antigen targets. PMID:28542223

Solution NMR Structures of Pyrenophora tritici-repentis ToxB and Its Inactive Homolog Reveal Potential Determinants of Toxin Activity*

PubMed Central

Nyarko, Afua; Singarapu, Kiran K.; Figueroa, Melania; Manning, Viola A.; Pandelova, Iovanna; Wolpert, Thomas J.; Ciuffetti, Lynda M.; Barbar, Elisar

2014-01-01

Pyrenophora tritici-repentis Ptr ToxB (ToxB) is a proteinaceous host-selective toxin produced by Pyrenophora tritici-repentis (P. tritici-repentis), a plant pathogenic fungus that causes the disease tan spot of wheat. One feature that distinguishes ToxB from other host-selective toxins is that it has naturally occurring homologs in non-pathogenic P. tritici-repentis isolates that lack toxic activity. There are no high-resolution structures for any of the ToxB homologs, or for any protein with >30% sequence identity, and therefore what underlies activity remains an open question. Here, we present the NMR structures of ToxB and its inactive homolog Ptr toxb. Both proteins adopt a β-sandwich fold comprising three strands in each half that are bridged together by two disulfide bonds. The inactive toxb, however, shows higher flexibility localized to the sequence-divergent β-sandwich half. The absence of toxic activity is attributed to a more open structure in the vicinity of one disulfide bond, higher flexibility, and residue differences in an exposed loop that likely impacts interaction with putative targets. We propose that activity is regulated by perturbations in a putative active site loop and changes in dynamics distant from the site of activity. Interestingly, the new structures identify AvrPiz-t, a secreted avirulence protein produced by the rice blast fungus, as a structural homolog to ToxB. This homology suggests that fungal proteins involved in either disease susceptibility such as ToxB or resistance such as AvrPiz-t may have a common evolutionary origin. PMID:25063993

Raft-Like Membrane Domains in Pathogenic Microorganisms

PubMed Central

Farnoud, Amir M.; Toledo, Alvaro M.; Konopka, James B.; Del Poeta, Maurizio; London, Erwin

2016-01-01

The lipid bilayer of the plasma membrane is thought to be compartmentalized by the presence of lipid-protein microdomains. In eukaryotic cells, microdomains composed of sterols and sphingolipids packed in a liquid-ordered state, commonly known as lipid rafts, are believed to exist. While less studied in bacterial cells, reports on the presence of sterol or protein-mediated microdomains in bacterial cell membranes are also appearing with increasing frequency. Recent efforts have been focused on addressing the biophysical and biochemical properties of lipid rafts. However, most studies have been focused on synthetic membranes, mammalian cells, and/or model, non-pathogenic microorganisms. Much less is known about microdomains in the plasma membrane of pathogenic microorganisms. This review attempts to provide an overview of the current state of knowledge of lipid rafts in pathogenic fungi and the developing field of microdomains in pathogenic bacteria. The current literature on the structure and function and of microdomains is reviewed and the potential role of microdomains in growth, pathogenesis, and drug resistance of pathogens are discussed. Better insight into the structure and function of membrane microdomains in pathogenic microorganisms might lead to a better understanding of the process of pathogenesis and development of raft-mediated approaches for new methods of therapy. PMID:26015285

Investigating the production of sexual resting structures in a plant pathogen reveals unexpected self-fertility and genotype-by-environment effects.

PubMed

Tollenaere, C; Laine, A-L

2013-08-01

The sexual stage of pathogens governs recombination patterns and often also provides means of surviving the off-season. Despite its importance for evolutionary potential and between-season epidemiology, sexual systems have not been carefully investigated for many important pathogens, and what generates variation in successful sexual reproduction of pathogens remains unexplored. We surveyed the sexually produced resting structures (chasmothecia) across 86 natural populations of fungal pathogen Podosphaera plantaginis (Ascomycota) naturally infecting Plantago lanceolata in the Åland archipelago, southwestern Finland. For this pathosystem, these resting structures are a key life-history stage, as more than half of the local pathogen populations go extinct every winter. We uncovered substantial variation in the level of chasmothecia produced among populations, ranging from complete absence to presence on all infected leaves. We found that chasmothecia developed within clonal isolates (single-strain cultures). Additionally, these clonal isolates all contained both MAT1-1-1 and MAT1-2-1 genes that characterize mating types in Ascomycetes. Hence, contrary to expectations, we conclude that this species is capable of haploid selfing. In controlled inoculations, we discovered that pathogen genotypes varied in their tendency to produce chasmothecia. Production of chasmothecia was also affected by ambient temperature (E) and by the interaction between temperature and pathogen genotype (G × E). These G, E and G × E effects found both at a European scale and within the Åland archipelago may partly explain the high variability observed among populations in chasmothecia levels. Consequently, they may be key drivers of the evolutionary potential and epidemiology of this highly dynamic pathosystem. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

Review of literature on climate change and forest diseases of western North America

Treesearch

John T. Kliejunas; Brian W. Geils; Jessie Micales Glaeser; Ellen Michaels Goheen; Paul Hennon; Mee-Sook Kim; Harry Kope; Jeff Stone; Rona Sturrock; Susan J. Frankel

2009-01-01

A summary of the literature on relationships between climate and various types of tree diseases, and the potential effects of climate change on pathogens in western North American forests is provided. Climate change generally will lead to reductions in tree health and will improve conditions for some highly damaging pathogens. Sections on abiotic diseases, declines,...

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...

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens.

PubMed

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Defelipe, Lucas; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo; Turjanski, Adrián G; Fernández Do Porto, Darío

2018-01-04

Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genetic diversity of Sclerotinia trifoliorum infecting chickpea based on mycelial compatibility grouping, rDNA introns and multi-locus haplotypes

USDA-ARS?s Scientific Manuscript database

Sclerotinia trifoliorum is recently reported as a new pathogen of chickpea in North America. The diversity and genetic structure of this heterothallic fungus is poorly understood. This study was designed to investigate the genetic structure and diversity of the pathogen. A collection of 133 isolates...

Mechanisms of Drug Resistance: Daptomycin Resistance

PubMed Central

Tran, Truc T.; Munita, Jose M.; Arias, Cesar A.

2016-01-01

Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction in clinical practice in 2003, DAP has become an important key front-line antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP-resistance (R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp, and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP resistance are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have offered novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria. PMID:26495887

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

PubMed Central

Lee, Ki-Young; Lee, Bong-Jin

2016-01-01

Bacterial toxin–antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein–protein interactions. Accumulating knowledge about the structure–function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems. PMID:27782085

Population genomics of Fusarium graminearum reveals signatures of divergent evolution within a major cereal pathogen

USDA-ARS?s Scientific Manuscript database

The cereal pathogen Fusarium graminearum is the primary cause of Fusarium head blight (FHB) and a significant threat to food safety and crop production. To elucidate population structure and identify genomic targets of selection within major FHB pathogen populations in North America we sequenced the...

The arms race between man and Mycobacterium tuberculosis: Time to regroup.

PubMed

Hoal, Eileen G; Dippenaar, Anzaan; Kinnear, Craig; van Helden, Paul D; Möller, Marlo

2017-08-23

An arms race is an appropriate metaphor to use for the interaction of man and Mycobacterium tuberculosis (M.tb) through the millennia. Estimates of the time of infection of modern humans with M.tb often pre-date the Out-of-Africa migration. Humans have adapted to the changing environment during the migration with respect to climate, food sources and encounters with local pathogens. More recently, there has been adaptation to the demographic changes brought about in the majority of the human population by the Neolithic revolution. By chance and/or selection, specific variants in immune defence have arisen in different population groups. These select for M.tb strains more fit to cause disease and be transmitted, sometimes by exploiting defence systems effective on other bacteria. The different selection pressures on the M.tb lineages carried by specific human groups have resulted in a worldwide M.tb population that is geographically structured according to the humans historically found there. A similar structure is seen with pathogens such as M. leprae and Helicobacter pylori. Modern M.tb strains have emerged which may be more fit, such as the Beijing lineage, leading to their rapid spread both in the areas where they arose, and into new areas after recent introduction. The speed at which this is occurring is outpacing coevolution for the time being. By using the results of genome wide and other association studies, as well as admixture mapping and 'natural experiments' in areas where both a number of populations, admixed populations, and a variety of M.tb strains occur, we can investigate the forces that have driven the coevolution of man and M.tb. The diversity of human and bacterial genetic background may be used in the future to discover and target the specific host-pathogen interactions leading to tuberculosis diseases, which suggests the potential for rational design of vaccines and host-directed therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence for Ecological Flexibility in the Cosmopolitan Genus Curtobacterium

PubMed Central

Chase, Alexander B.; Arevalo, Philip; Polz, Martin F.; Berlemont, Renaud; Martiny, Jennifer B. H.

2016-01-01

Assigning ecological roles to bacterial taxa remains imperative to understanding how microbial communities will respond to changing environmental conditions. Here we analyze the genus Curtobacterium, as it was found to be the most abundant taxon in a leaf litter community in southern California. Traditional characterization of this taxon predominantly associates it as the causal pathogen in the agricultural crops of dry beans. Therefore, we sought to investigate whether the abundance of this genus was because of its role as a plant pathogen or another ecological role. By collating >24,000 16S rRNA sequences with 120 genomes across the Microbacteriaceae family, we show that Curtobacterium has a global distribution with a predominant presence in soil ecosystems. Moreover, this genus harbors a high diversity of genomic potential for the degradation of carbohydrates, specifically with regards to structural polysaccharides. We conclude that Curtobacterium may be responsible for the degradation of organic matter within litter communities. PMID:27920771

Evanescent wave absorbance based fiber optic biosensor for label-free detection of E. coli at 280 nm wavelength.

PubMed

Bharadwaj, Reshma; Sai, V V R; Thakare, Kamini; Dhawangale, Arvind; Kundu, Tapanendu; Titus, Susan; Verma, Pradeep Kumar; Mukherji, Soumyo

2011-03-15

A novel label-free technique for the detection of pathogens based on evanescent wave absorbance (EWA) changes at 280 nm from a U-bent optical fiber sensor is demonstrated. Bending a decladded fiber into a U-shaped structure enhances the penetration depth of evanescent waves and hence sensitivity of the probe. We show that the enhanced EWA response from such U-bent probes, caused by the inherent optical absorbance properties of bacterial cells or biomolecules specifically bound to the sensor surface, can be exploited for the detection of pathogens. A portable optical set-up with a UV light emitting diode, a spectrometer and U-bent fiber optic probe of 200 μm core diameter, 0.75 mm bend radius and effective probe length of 1cm demonstrated an ability to detect less than 1000 cfu/ml. Copyright © 2011. Published by Elsevier B.V.

Evidence for Ecological Flexibility in the Cosmopolitan Genus Curtobacterium.

PubMed

Chase, Alexander B; Arevalo, Philip; Polz, Martin F; Berlemont, Renaud; Martiny, Jennifer B H

2016-01-01

Assigning ecological roles to bacterial taxa remains imperative to understanding how microbial communities will respond to changing environmental conditions. Here we analyze the genus Curtobacterium , as it was found to be the most abundant taxon in a leaf litter community in southern California. Traditional characterization of this taxon predominantly associates it as the causal pathogen in the agricultural crops of dry beans. Therefore, we sought to investigate whether the abundance of this genus was because of its role as a plant pathogen or another ecological role. By collating >24,000 16S rRNA sequences with 120 genomes across the Microbacteriaceae family, we show that Curtobacterium has a global distribution with a predominant presence in soil ecosystems. Moreover, this genus harbors a high diversity of genomic potential for the degradation of carbohydrates, specifically with regards to structural polysaccharides. We conclude that Curtobacterium may be responsible for the degradation of organic matter within litter communities.

[An influenza pandemic--a chronicle of an epidemic foretold].

PubMed

Bodas, Moran; Balicer, Ran D

2009-08-01

Influenza is a striking example of a viral disease in which pathogens constantly change and adaptation is of major significance in the appearance of seasonal outbreaks. These, in turn, can become widespread, possibly pandemic. Pandemic influenza differs from seasonal influenza outbreaks essentially by the emergence of a novel strain of the virus that, at times, is also characterized by enhanced pathogenicity and virulence. The last three influenza pandemics have risen from avian influenza strains, although other subtypes are equally capable of producing pandemic strains. For example, the Latest influenza outbreak, which was declared by the World Health Organization as a pandemic, is of swine origin. A severe influenza pandemic may have significant consequences on social and economicaL structures. Therefore, proper prior planning is essential for capabilities built-up to better cope with possibly worse future pandemics. Each influenza pandemic poses a different challenge, but, nevertheless the basic means for response are similar.

Rapid, Affordable, and Point-of-Care Water Monitoring Via a Microfluidic DNA Sensor and a Mobile Interface for Global Health

PubMed Central

Ghanbari, Sarah; Ravikumar, Anusha; Seubert, John; Figueira, Silvia

2013-01-01

Contaminated water is a serious concern in many developing countries with severe health consequences particularly for children. Current methods for monitoring waterborne pathogens are often time consuming, expensive, and labor intensive, making them not suitable for these regions. Electrochemical detection in a microfluidic platform offers many advantages such as portability, minimal use of instrumentation, and easy integration with electronics. In many parts of the world, however, the required equipment for pathogen detection through electrochemical sensors is either not available or insufficiently portable, and operators may not be trained to use these sensors and interpret results, ultimately preventing its wide adoption. Counterintuitively, these same regions often have an extensive mobile phone infrastructure, suggesting the possibility of integrating electrochemical detection of bacterial pathogens with a mobile platform. Toward a solution to water quality interventions, we demonstrate a microfluidic electrochemical sensor combined with a mobile interface that detects the sequences from bacterial pathogens, suitable for rapid, affordable, and point-of-care water monitoring. We employ the transduction of DNA hybridization into a readily detectable electric signal by means of a conformational change of DNA stem-loop structure. Using this platform, we successfully demonstrate the detection of as low as 100 nM E. coli sequences and the automatic interpretation and mapping of the detection results via a mobile application. PMID:27170858

Cell wall proteome of pathogenic fungi.

PubMed

Karkowska-Kuleta, Justyna; Kozik, Andrzej

2015-01-01

A fast development of a wide variety of proteomic techniques supported by mass spectrometry coupled with high performance liquid chromatography has been observed in recent years. It significantly contributes to the progress in research on the cell wall, very important part of the cells of pathogenic fungi. This complicated structure composed of different polysaccharides, proteins, lipids and melanin, plays a key role in interactions with the host during infection. Changes in the set of the surface-exposed proteins under different environmental conditions provide an effective way for pathogens to respond, adapt and survive in the new niches of infection. This work summarizes the current state of knowledge on proteins, studied both qualitatively and quantitatively, and found within the cell wall of fungal pathogens for humans, including Candida albicans, Candida glabrata, Aspergillus fumigatus, Cryptococcus neoformans and other medically important fungi. The described proteomic studies involved the isolation and fractionation of particular sets of proteins of interest with various techniques, often based on differences in their linkages to the polysaccharide scaffold. Furthermore, the proteinaceous contents of extracellular vesicles ("virulence bags") of C. albicans, C. neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis are compared, because their production can partially explain the problem of non-classical protein secretion by fungi. The role assigned to surface-exposed proteins in pathogenesis of fungal infections is enormously high, thus justifying the need for further investigation of cell wall proteomes.

Chemical ecology of animal and human pathogen vectors in a changing global climate.

PubMed

Pickett, John A; Birkett, Michael A; Dewhirst, Sarah Y; Logan, James G; Omolo, Maurice O; Torto, Baldwyn; Pelletier, Julien; Syed, Zainulabeuddin; Leal, Walter S

2010-01-01

Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on "The Chemical Ecology of Disease Vectors" at the 25th Annual ISCE meeting in Neuchatel, Switzerland. The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.

Genomic survey of pathogenicity determinants and VNTR markers in the cassava bacterial pathogen Xanthomonas axonopodis pv. Manihotis strain CIO151.

PubMed

Arrieta-Ortiz, Mario L; Rodríguez-R, Luis M; Pérez-Quintero, Álvaro L; Poulin, Lucie; Díaz, Ana C; Arias Rojas, Nathalia; Trujillo, Cesar; Restrepo Benavides, Mariana; Bart, Rebecca; Boch, Jens; Boureau, Tristan; Darrasse, Armelle; David, Perrine; Dugé de Bernonville, Thomas; Fontanilla, Paula; Gagnevin, Lionel; Guérin, Fabien; Jacques, Marie-Agnès; Lauber, Emmanuelle; Lefeuvre, Pierre; Medina, Cesar; Medina, Edgar; Montenegro, Nathaly; Muñoz Bodnar, Alejandra; Noël, Laurent D; Ortiz Quiñones, Juan F; Osorio, Daniela; Pardo, Carolina; Patil, Prabhu B; Poussier, Stéphane; Pruvost, Olivier; Robène-Soustrade, Isabelle; Ryan, Robert P; Tabima, Javier; Urrego Morales, Oscar G; Vernière, Christian; Carrere, Sébastien; Verdier, Valérie; Szurek, Boris; Restrepo, Silvia; López, Camilo; Koebnik, Ralf; Bernal, Adriana

2013-01-01

Xanthomonas axonopodis pv. manihotis (Xam) is the causal agent of bacterial blight of cassava, which is among the main components of human diet in Africa and South America. Current information about the molecular pathogenicity factors involved in the infection process of this organism is limited. Previous studies in other bacteria in this genus suggest that advanced draft genome sequences are valuable resources for molecular studies on their interaction with plants and could provide valuable tools for diagnostics and detection. Here we have generated the first manually annotated high-quality draft genome sequence of Xam strain CIO151. Its genomic structure is similar to that of other xanthomonads, especially Xanthomonas euvesicatoria and Xanthomonas citri pv. citri species. Several putative pathogenicity factors were identified, including type III effectors, cell wall-degrading enzymes and clusters encoding protein secretion systems. Specific characteristics in this genome include changes in the xanthomonadin cluster that could explain the lack of typical yellow color in all strains of this pathovar and the presence of 50 regions in the genome with atypical nucleotide composition. The genome sequence was used to predict and evaluate 22 variable number of tandem repeat (VNTR) loci that were subsequently demonstrated as polymorphic in representative Xam strains. Our results demonstrate that Xanthomonas axonopodis pv. manihotis strain CIO151 possesses ten clusters of pathogenicity factors conserved within the genus Xanthomonas. We report 126 genes that are potentially unique to Xam, as well as potential horizontal transfer events in the history of the genome. The relation of these regions with virulence and pathogenicity could explain several aspects of the biology of this pathogen, including its ability to colonize both vascular and non-vascular tissues of cassava plants. A set of 16 robust, polymorphic VNTR loci will be useful to develop a multi-locus VNTR analysis scheme for epidemiological surveillance of this disease.

Genomic Survey of Pathogenicity Determinants and VNTR Markers in the Cassava Bacterial Pathogen Xanthomonas axonopodis pv. Manihotis Strain CIO151

PubMed Central

Arrieta-Ortiz, Mario L.; Rodríguez-R, Luis M.; Pérez-Quintero, Álvaro L.; Poulin, Lucie; Díaz, Ana C.; Arias Rojas, Nathalia; Trujillo, Cesar; Restrepo Benavides, Mariana; Bart, Rebecca; Boch, Jens; Boureau, Tristan; Darrasse, Armelle; David, Perrine; Dugé de Bernonville, Thomas; Fontanilla, Paula; Gagnevin, Lionel; Guérin, Fabien; Jacques, Marie-Agnès; Lauber, Emmanuelle; Lefeuvre, Pierre; Medina, Cesar; Medina, Edgar; Montenegro, Nathaly; Muñoz Bodnar, Alejandra; Noël, Laurent D.; Ortiz Quiñones, Juan F.; Osorio, Daniela; Pardo, Carolina; Patil, Prabhu B.; Poussier, Stéphane; Pruvost, Olivier; Robène-Soustrade, Isabelle; Ryan, Robert P.; Tabima, Javier; Urrego Morales, Oscar G.; Vernière, Christian; Carrere, Sébastien; Verdier, Valérie; Szurek, Boris; Restrepo, Silvia; López, Camilo

2013-01-01

Xanthomonas axonopodis pv. manihotis (Xam) is the causal agent of bacterial blight of cassava, which is among the main components of human diet in Africa and South America. Current information about the molecular pathogenicity factors involved in the infection process of this organism is limited. Previous studies in other bacteria in this genus suggest that advanced draft genome sequences are valuable resources for molecular studies on their interaction with plants and could provide valuable tools for diagnostics and detection. Here we have generated the first manually annotated high-quality draft genome sequence of Xam strain CIO151. Its genomic structure is similar to that of other xanthomonads, especially Xanthomonas euvesicatoria and Xanthomonas citri pv. citri species. Several putative pathogenicity factors were identified, including type III effectors, cell wall-degrading enzymes and clusters encoding protein secretion systems. Specific characteristics in this genome include changes in the xanthomonadin cluster that could explain the lack of typical yellow color in all strains of this pathovar and the presence of 50 regions in the genome with atypical nucleotide composition. The genome sequence was used to predict and evaluate 22 variable number of tandem repeat (VNTR) loci that were subsequently demonstrated as polymorphic in representative Xam strains. Our results demonstrate that Xanthomonas axonopodis pv. manihotis strain CIO151 possesses ten clusters of pathogenicity factors conserved within the genus Xanthomonas. We report 126 genes that are potentially unique to Xam, as well as potential horizontal transfer events in the history of the genome. The relation of these regions with virulence and pathogenicity could explain several aspects of the biology of this pathogen, including its ability to colonize both vascular and non-vascular tissues of cassava plants. A set of 16 robust, polymorphic VNTR loci will be useful to develop a multi-locus VNTR analysis scheme for epidemiological surveillance of this disease. PMID:24278159

Bioinformatic Analysis of Pathogenic Missense Mutations of Activin Receptor Like Kinase 1 Ectodomain

PubMed Central

Scotti, Claudia; Olivieri, Carla; Boeri, Laura; Canzonieri, Cecilia; Ornati, Federica; Buscarini, Elisabetta; Pagella, Fabio; Danesino, Cesare

2011-01-01

Activin A receptor, type II-like kinase 1 (also called ALK1), is a serine-threonine kinase predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. The study of the structural effects of mutations is crucial to understand their pathogenic mechanism. However, while an X-ray structure of ALK1 intracellular domain has recently become available (PDB ID: 3MY0), structure determination of ALK1 ectodomain (ALK1EC) has been elusive so far. We here describe the building of a homology model for ALK1EC, followed by an extensive bioinformatic analysis, based on a set of 38 methods, of the effect of missense mutations at the sequence and structural level. ALK1EC potential interaction mode with its ligand BMP9 was then predicted combining modelling and docking data. The calculated model of the ALK1EC allowed mapping and a preliminary characterization of HHT2 associated mutations. Major structural changes and loss of stability of the protein were predicted for several mutations, while others were found to interfere mainly with binding to BMP9 or other interactors, like Endoglin (CD105), whose encoding ENG gene (9q34) mutations are known to cause type 1 HHT. This study gives a preliminary insight into the potential structure of ALK1EC and into the structural effects of HHT2 associated mutations, which can be useful to predict the potential effect of each single mutation, to devise new biological experiments and to interpret the biological significance of new mutations, private mutations, or non-synonymous polymorphisms. PMID:22028876

Emergence of pathogenic and multiple-antibiotic-resistant Macrococcus caseolyticus in commercial broiler chickens.

PubMed

Li, Gen; Du, Xusheng; Zhou, Defang; Li, Chengui; Huang, Libo; Zheng, Qiankun; Cheng, Ziqiang

2018-05-25

Macrococcus caseolyticus is generally considered to be a non-pathogenic bacterium that does not cause human or animal diseases. However, recently, a strain of M. caseolyticus (SDLY strain) that causes high mortality rates was isolated from commercial broiler chickens in China. The main pathological changes caused by SDLY included caseous exudation in cranial cavities, inflammatory infiltration, haemorrhages and multifocal necrosis in various organs. The whole genome of the SDLY strain was sequenced and was compared with that of the non-pathogenic JCSC5402 strain of M. caseolyticus. The results showed that the SDLY strain harboured a large quantity of mutations, antibiotic resistance genes and numerous insertions and deletions of virulence genes. In particular, among the inserted genes, there is a cluster of eight connected genes associated with the synthesis of capsular polysaccharide. This cluster encodes a transferase and capsular polysaccharide synthase, promotes the formation of capsules and causes changes in pathogenicity. Electron microscopy revealed a distinct capsule surrounding the SDLY strain. The pathogenicity test showed that the SDLY strain could cause significant clinical symptoms and pathological changes in both SPF chickens and mice. In addition, these clinical symptoms and pathological changes were the same as those observed in field cases. Furthermore, the anti-microbial susceptibility test demonstrated that the SDLY strain exhibits multiple-antibiotic resistance. The emergence of pathogenic M. caseolyticus indicates that more attention should be paid to the effects of this micro-organism on both poultry and public health. © 2018 Blackwell Verlag GmbH.

Phytophthora capsici-tomato interaction features dramatic shifts in gene expression associated with a hemi-biotrophic lifestyle.

PubMed

Jupe, Julietta; Stam, Remco; Howden, Andrew J M; Morris, Jenny A; Zhang, Runxuan; Hedley, Pete E; Huitema, Edgar

2013-06-25

Plant-microbe interactions feature complex signal interplay between pathogens and their hosts. Phytophthora species comprise a destructive group of fungus-like plant pathogens, collectively affecting a wide range of plants important to agriculture and natural ecosystems. Despite the availability of genome sequences of both hosts and microbes, little is known about the signal interplay between them during infection. In particular, accurate descriptions of coordinate relationships between host and microbe transcriptional programs are lacking. Here, we explore the molecular interaction between the hemi-biotrophic broad host range pathogen Phytophthora capsici and tomato. Infection assays and use of a composite microarray allowed us to unveil distinct changes in both P. capsici and tomato transcriptomes, associated with biotrophy and the subsequent switch to necrotrophy. These included two distinct transcriptional changes associated with early infection and the biotrophy to necrotrophy transition that may contribute to infection and completion of the P. capsici lifecycle Our results suggest dynamic but highly regulated transcriptional programming in both host and pathogen that underpin P. capsici disease and hemi-biotrophy. Dynamic expression changes of both effector-coding genes and host factors involved in immunity, suggests modulation of host immune signaling by both host and pathogen. With new unprecedented detail on transcriptional reprogramming, we can now explore the coordinate relationships that drive host-microbe interactions and the basic processes that underpin pathogen lifestyles. Deliberate alteration of lifestyle-associated transcriptional changes may allow prevention or perhaps disruption of hemi-biotrophic disease cycles and limit damage caused by epidemics.

Temporal Genetic Dynamics of an Experimental, Biparental Field Population of Phytophthora capsici

PubMed Central

Carlson, Maryn O.; Gazave, Elodie; Gore, Michael A.; Smart, Christine D.

2017-01-01

Defining the contributions of dispersal, reproductive mode, and mating system to the population structure of a pathogenic organism is essential to estimating its evolutionary potential. After introduction of the devastating plant pathogen, Phytophthora capsici, into a grower’s field, a lack of aerial spore dispersal restricts migration. Once established, coexistence of both mating types results in formation of overwintering recombinant oospores, engendering persistent pathogen populations. To mimic these conditions, in 2008, we inoculated a field with two P. capsici isolates of opposite mating type. We analyzed pathogenic isolates collected in 2009–2013 from this experimental population, using genome-wide single-nucleotide polymorphism markers. By tracking heterozygosity across years, we show that the population underwent a generational shift; transitioning from exclusively F1 in 2009–2010, to multi-generational in 2011, and ultimately all inbred in 2012–2013. Survival of F1 oospores, characterized by heterozygosity excess, coupled with a low rate of selfing, delayed declines in heterozygosity due to inbreeding and attainment of equilibrium genotypic frequencies. Large allele and haplotype frequency changes in specific genomic regions accompanied the generational shift, representing putative signatures of selection. Finally, we identified an approximately 1.6 Mb region associated with mating type determination, constituting the first detailed genomic analysis of a mating type region (MTR) in Phytophthora. Segregation patterns in the MTR exhibited tropes of sex-linkage, where maintenance of allele frequency differences between isolates of opposite mating type was associated with elevated heterozygosity despite inbreeding. Characterizing the trajectory of this experimental system provides key insights into the processes driving persistent, sexual pathogen populations. PMID:28348576

How light affects the life of Botrytis.

PubMed

Schumacher, Julia

2017-09-01

Fungi, like other organisms, actively sense the environmental light conditions in order to drive adaptive responses, including protective mechanisms against the light-associated stresses, and to regulate development. Ecological niches are characterized by different light regimes, for instance light is absent underground, and light spectra from the sunlight are changed underwater or under the canopy of foliage due to the absorption of distinct wavelengths by bacterial, algal and plant pigments. Considering the fact that fungi have evolved to adapt to their habitats, the complexities of their 'visual' systems may vary significantly. Fungi that are pathogenic on plants experience a special light regime because the host always seeks the optimum light conditions for photosynthesis - and the pathogen has to cope with this environment. When the pathogen lives under the canopy and is indirectly exposed to sunlight, it is confronted with an altered light spectrum enriched for green and far-red light. Botrytis cinerea, the gray mold fungus, is an aggressive plant pathogen mainly infecting the above-ground parts of the plant. As outlined in this review, the Leotiomycete maintains a highly sophisticated light signaling machinery, integrating (near)-UV, blue, green, red and far-red light signals by use of at least eleven potential photoreceptors to trigger a variety of responses, i.e. protection (pigmentation, enzymatic systems), morphogenesis (conidiation, apothecial development), entrainment of a circadian clock, and positive and negative tropism of multicellular (conidiophores, apothecia) and unicellular structures (conidial germ tubes). In that sense, 'looking through the eyes' of this plant pathogen will expand our knowledge of fungal photobiology. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Efficient local behavioral-change strategies to reduce the spread of epidemics in networks

NASA Astrophysics Data System (ADS)

Bu, Yilei; Gregory, Steve; Mills, Harriet L.

2013-10-01

It has recently become established that the spread of infectious diseases between humans is affected not only by the pathogen itself but also by changes in behavior as the population becomes aware of the epidemic, for example, social distancing. It is also well known that community structure (the existence of relatively densely connected groups of vertices) in contact networks influences the spread of disease. We propose a set of local strategies for social distancing, based on community structure, that can be employed in the event of an epidemic to reduce the epidemic size. Unlike most social distancing methods, ours do not require individuals to know the disease state (infected or susceptible, etc.) of others, and we do not make the unrealistic assumption that the structure of the entire contact network is known. Instead, the recommended behavior change is based only on an individual's local view of the network. Each individual avoids contact with a fraction of his/her contacts, using knowledge of his/her local network to decide which contacts should be avoided. If the behavior change occurs only when an individual becomes ill or aware of the disease, these strategies can substantially reduce epidemic size with a relatively small cost, measured by the number of contacts avoided.

Cu,Zn superoxide dismutase structure from a microbial pathogen establishes a class with a conserved dimer interface.

PubMed

Forest, K T; Langford, P R; Kroll, J S; Getzoff, E D

2000-02-11

Macrophages and neutrophils protect animals from microbial infection in part by issuing a burst of toxic superoxide radicals when challenged. To counteract this onslaught, many Gram-negative bacterial pathogens possess periplasmic Cu,Zn superoxide dismutases (SODs), which act on superoxide to yield molecular oxygen and hydrogen peroxide. We have solved the X-ray crystal structure of the Cu,Zn SOD from Actinobacillus pleuropneumoniae, a major porcine pathogen, by molecular replacement at 1.9 A resolution. The structure reveals that the dimeric bacterial enzymes form a structurally homologous class defined by a water-mediated dimer interface, and share with all Cu,Zn SODs the Greek-key beta-barrel subunit fold with copper and zinc ions located at the base of a deep loop-enclosed active-site channel. Our structure-based sequence alignment of the bacterial enzymes explains the monomeric nature of at least two of these, and suggests that there may be at least one additional structural class for the bacterial SODs. Two metal-mediated crystal contacts yielded our C222(1) crystals, and the geometry of these sites could be engineered into proteins recalcitrant to crystallization in their native form. This work highlights structural differences between eukaryotic and prokaryotic Cu,Zn SODs, as well as similarities and differences among prokaryotic SODs, and lays the groundwork for development of antimicrobial drugs that specifically target periplasmic Cu,Zn SODs of bacterial pathogens. Copyright 12000 Academic Press.

Disruption of the Gut Ecosystem by Antibiotics

PubMed Central

2018-01-01

The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state. PMID:29214770

Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack.

PubMed

De Vos, Martin; Van Oosten, Vivian R; Van Poecke, Remco M P; Van Pelt, Johan A; Pozo, Maria J; Mueller, Martin J; Buchala, Antony J; Métraux, Jean-Pierre; Van Loon, L C; Dicke, Marcel; Pieterse, Corné M J

2005-09-01

Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and E occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.

Population structure of the emerging plant pathogen Phytophthora ramorum on the west coast of the United States

Treesearch

S. Prospero; E.M. Hansen; N.J. Grünwald; J. Britt; L.M. Winton.

2009-01-01

Phytophthora ramorum is a devastating pathogen in native forests in California and southwestern Oregon and in nursery crops in California, Oregon and Washington. In this study we analyzed the population structure of P. ramorum in the west coast (CA, OR, and WA) of the United States by screening 579 isolates recovered...

Coarse-scale population structure of pathogenic Armillaria species in a mixed-conifer forest in the Blue Mountains of northeast Oregon.

Treesearch

B.A. Ferguson; T.A. Dreisbach; C.G. Parks; G.M. Filip; C.L. Schmitt

2003-01-01

The coarse-scale population structure of pathogenic Armillaria (Fr.) Staude species was determined on approximately 16 100 ha Of relatively dry, mixed-conifer forest in the Blue Mountains of northeast Oregon. Sampling of recently dead or live, symptomatic conifers produced 112 isolates of Armillaria from six tree species.

Pathogen survival trajectories: an eco-environmental approach to the modeling of human campylobacteriosis ecology.

PubMed Central

Skelly, Chris; Weinstein, Phil

2003-01-01

Campylobacteriosis, like many human diseases, has its own ecology in which the propagation of human infection and disease depends on pathogen survival and finding new hosts in order to replicate and sustain the pathogen population. The complexity of this process, a process common to other enteric pathogens, has hampered control efforts. Many unknowns remain, resulting in a poorly understood disease ecology. To provide structure to these unknowns and help direct further research and intervention, we propose an eco-environmental modeling approach for campylobacteriosis. This modeling approach follows the pathogen population as it moves through the environments that define the physical structure of its ecology. In this paper, we term the ecologic processes and environments through which these populations move "pathogen survival trajectories." Although such a modeling approach could have veterinary applications, our emphasis is on human campylobacteriosis and focuses on human exposures to Campylobacter through feces, food, and aquatic environments. The pathogen survival trajectories that lead to human exposure include ecologic filters that limit population size, e.g., cooking food to kill Campylobacter. Environmental factors that influence the size of the pathogen reservoirs include temperature, nutrient availability, and moisture availability during the period of time the pathogen population is moving through the environment between infected and susceptible hosts. We anticipate that the modeling approach proposed here will work symbiotically with traditional epidemiologic and microbiologic research to help guide and evaluate the acquisition of new knowledge about the ecology, eventual intervention, and control of campylobacteriosis. PMID:12515674

Impact of Insertion Sequences and Recombination on the Population Structure of Staphylococcus haemolyticus.

PubMed

Bouchami, Ons; de Lencastre, Herminia; Miragaia, Maria

2016-01-01

Staphylococcus haemolyticus is one of the most common pathogens associated with medical-device related infections, but its molecular epidemiology is poorly explored. In the current study, we aimed to better understand the genetic mechanisms contributing to S. haemolyticus diversity in the hospital environment and their impact on the population structure and clinical relevant phenotypic traits. The analysis of a representative S. haemolyticus collection by multilocus sequence typing (MLST) has identified a single highly prevalent and diverse genetic lineage of nosocomial S. haemolyticus clonal complex (CC) 29 accounting for 91% of the collection of isolates disseminated worldwide. The examination of the sequence changes at MLST loci during clonal diversification showed that recombination had a higher impact than mutation in shaping the S. haemolyticus population. Also, we ascertained that another mechanism contributing significantly to clonal diversification and adaptation was mediated by insertion sequence (IS) elements. We found that all nosocomial S. haemolyticus, belonging to different STs, were rich in IS1272 copies, as determined by Southern hybridization of macrorestriction patterns. In particular, we observed that the chromosome of a S. haemolyticus strain within CC29 was highly unstable during serial growth in vitro which paralleled with IS1272 transposition events and changes in clinically relevant phenotypic traits namely, mannitol fermentation, susceptibility to beta-lactams, biofilm formation and hemolysis. Our results suggest that recombination and IS transposition might be a strategy of adaptation, evolution and pathogenicity of the major S. haemolyticus prevalent lineage in the hospital environment.

Impact of Insertion Sequences and Recombination on the Population Structure of Staphylococcus haemolyticus

PubMed Central

Bouchami, Ons; de Lencastre, Herminia; Miragaia, Maria

2016-01-01

Staphylococcus haemolyticus is one of the most common pathogens associated with medical-device related infections, but its molecular epidemiology is poorly explored. In the current study, we aimed to better understand the genetic mechanisms contributing to S. haemolyticus diversity in the hospital environment and their impact on the population structure and clinical relevant phenotypic traits. The analysis of a representative S. haemolyticus collection by multilocus sequence typing (MLST) has identified a single highly prevalent and diverse genetic lineage of nosocomial S. haemolyticus clonal complex (CC) 29 accounting for 91% of the collection of isolates disseminated worldwide. The examination of the sequence changes at MLST loci during clonal diversification showed that recombination had a higher impact than mutation in shaping the S. haemolyticus population. Also, we ascertained that another mechanism contributing significantly to clonal diversification and adaptation was mediated by insertion sequence (IS) elements. We found that all nosocomial S. haemolyticus, belonging to different STs, were rich in IS1272 copies, as determined by Southern hybridization of macrorestriction patterns. In particular, we observed that the chromosome of a S. haemolyticus strain within CC29 was highly unstable during serial growth in vitro which paralleled with IS1272 transposition events and changes in clinically relevant phenotypic traits namely, mannitol fermentation, susceptibility to beta-lactams, biofilm formation and hemolysis. Our results suggest that recombination and IS transposition might be a strategy of adaptation, evolution and pathogenicity of the major S. haemolyticus prevalent lineage in the hospital environment. PMID:27249649

Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

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

Gangi Setty, Thanuja; Cho, Christine; Govindappa, Sowmya

2014-07-01

Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which oftenmore » takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.« less

Evaluation of the effect of cigarette smoking on the olfactory neuroepithelium of New Zealand white rabbit, using scanning electron microscope.

PubMed

Iskander, Nagi M; El-Hennawi, Diaa M; Yousef, Tarek F; El-Tabbakh, Mohammed T; Elnahriry, Tarek A

2017-06-01

To detect ultra-structural changes of Rabbit's olfactory neuro-epithelium using scanning electron microscope after exposure to cigarette smoking. Sixty six rabbits (Pathogen free New Zealand white rabbits weighing 1-1.5 kg included in the study were randomly assigned into one of three groups: control group did not expose to cigarette smoking, study group 1 was exposed to cigarette smoking for 3 months and study group 2 was exposed to cigarette smoking 3 months and then stopped for 2 months. Olfactory neuro-epithelium from all rabbits were dissected and examined under Philips XL-30 scanning electron microscope. Changes that were found in the rabbits of study group 1 in comparison to control group were loss of microvilli of sustentacular cells (p = 0.016) and decreases in distribution of specialized cilia of olfactory receptor cells (p = 0.046). Also respiratory metaplasia was detected. These changes were reversible in study group 2. Cigarette smoking causes ultra-structural changes in olfactory neuro-epithelium which may explain why smell was affected in cigarette smokers. Most of these changes were reversible after 45 days of cessation of cigarette smoking to the rabbits.

Host-induced aneuploidy and phenotypic diversification in the Sudden Oak Death pathogen Phytophthora ramorum

USDA-ARS?s Scientific Manuscript database

Aneuploidy can result in significant phenotypic changes, which can sometimes be selectively advantageous. For example, aneuploidy confers resistance to antifungal drugs in human pathogenic fungi. Aneuploidy has also been observed in invasive fungal and oomycete plant pathogens in the field. Environm...

Diversity and Evolution in the Genome of Clostridium difficile

PubMed Central

Knight, Daniel R.; Elliott, Briony; Chang, Barbara J.; Perkins, Timothy T.

2015-01-01

SUMMARY Clostridium difficile infection (CDI) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. In the last 2 decades, PCR- and sequence-based techniques, particularly whole-genome sequencing (WGS), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. C. difficile is taxonomically distinct from many other well-known clostridia, with a diverse population structure comprising hundreds of strain types spread across at least 6 phylogenetic clades. The C. difficile species is defined by a large diverse pangenome with extreme levels of evolutionary plasticity that has been shaped over long time periods by gene flux and recombination, often between divergent lineages. These evolutionary events are in response to environmental and anthropogenic activities and have led to the rapid emergence and worldwide dissemination of virulent clonal lineages. Moreover, genome analysis of large clinically relevant data sets has improved our understanding of CDI outbreaks, transmission, and recurrence. The epidemiology of CDI has changed dramatically over the last 15 years, and CDI may have a foodborne or zoonotic etiology. The WGS era promises to continue to redefine our view of this significant pathogen. PMID:26085550

Inhibitors Selective for Mycobacterial Versus Human Proteasomes

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

Lin, G.; Li, D; Sorio de Carvalho, L

Many anti-infectives inhibit the synthesis of bacterial proteins, but none selectively inhibits their degradation. Most anti-infectives kill replicating pathogens, but few preferentially kill pathogens that have been forced into a non-replicating state by conditions in the host. To explore these alternative approaches we sought selective inhibitors of the proteasome of Mycobacterium tuberculosis. Given that the proteasome structure is extensively conserved, it is not surprising that inhibitors of all chemical classes tested have blocked both eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially more potent on proteasomes of pathogens than of their hosts. Here we show that certain oxathiazol-2-onemore » compounds kill non-replicating M.?tuberculosis and act as selective suicide-substrate inhibitors of the M.?tuberculosis proteasome by cyclocarbonylating its active site threonine. Major conformational changes protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of an oxazolidin-2-one and preventing regeneration of active protease. Residues outside the active site whose hydrogen bonds stabilize the critical loop before and after it moves are extensively non-conserved. This may account for the ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome potently and irreversibly while largely sparing the human homologue.« less

Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on Surveillance - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2013-2016.

PubMed

Marder, Ellyn P; Cieslak, Paul R; Cronquist, Alicia B; Dunn, John; Lathrop, Sarah; Rabatsky-Ehr, Therese; Ryan, Patricia; Smith, Kirk; Tobin-D'Angelo, Melissa; Vugia, Duc J; Zansky, Shelley; Holt, Kristin G; Wolpert, Beverly J; Lynch, Michael; Tauxe, Robert; Geissler, Aimee L

2017-04-21

Foodborne diseases represent a substantial public health concern in the United States. CDC's Foodborne Diseases Active Surveillance Network (FoodNet) monitors cases reported from 10 U.S. sites* of laboratory-diagnosed infections caused by nine enteric pathogens commonly transmitted through food. This report describes preliminary surveillance data for 2016 on the nine pathogens and changes in incidences compared with 2013-2015. In 2016, FoodNet identified 24,029 infections, 5,512 hospitalizations, and 98 deaths caused by these pathogens. The use of culture-independent diagnostic tests (CIDTs) by clinical laboratories to detect enteric pathogens has been steadily increasing since FoodNet began surveying clinical laboratories in 2010 (1). CIDTs complicate the interpretation of FoodNet surveillance data because pathogen detection could be affected by changes in health care provider behaviors or laboratory testing practices (2). Health care providers might be more likely to order CIDTs because these tests are quicker and easier to use than traditional culture methods, a circumstance that could increase pathogen detection (3). Similarly, pathogen detection could also be increasing as clinical laboratories adopt DNA-based syndromic panels, which include pathogens not often included in routine stool culture (4,5). In addition, CIDTs do not yield isolates, which public health officials rely on to distinguish pathogen subtypes, determine antimicrobial resistance, monitor trends, and detect outbreaks. To obtain isolates for infections identified by CIDTs, laboratories must perform reflex culture † ; if clinical laboratories do not, the burden of culturing falls to state public health laboratories, which might not be able to absorb that burden as the adoption of these tests increases (2). Strategies are needed to preserve access to bacterial isolates for further characterization and to determine the effect of changing trends in testing practices on surveillance.

Host-pathogen interactions in plants. Plants, when exposed to oligosaccharides of fungal origin, defend themselves by accumulating antibiotics

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

Albersheim, P.; Valent, B.S.

1978-01-01

The ability to synthesize phytoalexins is a mechanism by which plants are able to stop the growth of microorganisms which have not become pathogenic on the phytoalexin-producing plant. Although not sufficient for its complete resistence to pathogens, an ability to synthesize phytoalexins is likely to be one essential criterion for a plant to be resistant to pathogens. Plants recognize the presence of many nonpathogenic fungi by recognizing a structural component of the mycelial walls of the fungi. Other microorganisms do not have structural glucans in their walls. There is, likely, some other components of bacteria, for instance, which act asmore » elicitors in plants since it is known that they do elicit phytoalexin production in plants. The authors are attempting to identify a bacterial elicitor. It is known that the soybean pathogen Phytophthora magasperma is an oligosaccharide composed only of glucose. This is of general biological interest since it shows that oligosaccharides can act as regulatory molecules.« less

Network biology discovers pathogen contact points in host protein-protein interactomes.

PubMed

Ahmed, Hadia; Howton, T C; Sun, Yali; Weinberger, Natascha; Belkhadir, Youssef; Mukhtar, M Shahid

2018-06-13

In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1 MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1 MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSI LRR ) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

1-(2-aminophenyl)-1H-1,2,3-triazole-4-carboxylic acid: activity against Gram-positive and Gram-negative pathogens including Vibrio cholerae

NASA Astrophysics Data System (ADS)

Maji, Krishnendu; Haldar, Debasish

2017-10-01

We report a new synthetic aromatic ε-amino acid containing a triazole moiety with antimicrobial potential against Gram-positive, Gram-negative and pathogenic bacteria including Vibrio cholerae. Structure-property relationship studies revealed that all the functional groups are essential to enhance the antimicrobial activity. The 1-(2-aminophenyl)-1H-1,2,3-triazole-4-carboxylic acid was synthesized by click chemistry. From X-ray crystallography, the amino acid adopts a kink-like structure where the phenyl and triazole rings are perpendicular to each other and the amine and acid groups maintain an angle of 60°. The agar diffusion test shows that the amino acid has significant antibacterial activity. The liquid culture test exhibits that the minimum inhibitory concentration (MIC) value for Bacillus subtilis and Vibrio cholerae is 59.5 µg ml-1. FE-SEM experiments were performed to study the morphological changes of bacterial shape after treatment with compound 1. The antimicrobial activity of the amino acid was further studied by DNA binding and degradation study, protein binding, dye-binding assay and morphological analysis. Moreover, the amino acid does not have any harmful effect on eukaryotes.

Bactericidal and antibiofilm activity of bactenecin-derivative peptides against the food-pathogen Listeria monocytogenes: New perspectives for food processing industry.

PubMed

Palmieri, Gianna; Balestrieri, Marco; Capuano, Federico; Proroga, Yolande T R; Pomilio, Francesco; Centorame, Patrizia; Riccio, Alessia; Marrone, Raffaele; Anastasio, Aniello

2018-08-20

Antimicrobial peptides have received great attention for their potential benefits to extend the shelf-life of food-products. Innate defense regulator peptide-1018 (IDR-1018) represents a promising candidate for such applications, due to its broad-spectrum antimicrobial activity, although food-isolated pathogens have been poorly investigated. Herein, we describe the design and the structural-functional characterization of a new 1018-derivative peptide named 1018-K6, in which the alanine in position 6 was replaced with a lysine. Spectroscopic analysis revealed a noticeable switch from β-sheet to helical conformations of 1018-K6 respect to IDR-1018, with a faster folding kinetic and increased structural stability. Moreover, 1018-K6 evidenced a significant antibiofilm/bactericidal efficiency specifically against Listeria monocytogenes isolates from food-products and food-processing environments, belonging to serotype 4b involved in the majority of human-listeriosis cases, with EC 50 values two- five-fold lower than those measured for IDR-1018. Therefore, a single amino-acid substitution in IDR-1018 sequence produced severe changes in peptide conformation and antimicrobial performances. Published by Elsevier B.V.

Rapid detection of biofilms and adherent pathogens using scanning confocal laser microscopy and episcopic differential interference contrast microscopy.

PubMed

Keevil, C W

2003-01-01

Knowledge of biofilm structure and function has changed significantly in the last few years due to advances in light microscopy. One pertinent example is the use of scanning confocal laser microscopy (SCLM) to visualise corrosion pits caused by the biofilm mosaic footprint on corroding metal surfaces. Nevertheless, SCLM has some limitations as to its widespread use, including cost, inability to observe motile bacteria and eukaryotic grazers within biofilms, and difficulty to scan a curved surface. By contrast, episcopic differential interference contrast (EDIC) microscopy has provided a rapid, real time analysis of biofilms on opaque, curved, natural or man-made surfaces without the need for cover slips and oil. EDIC, coupled with epi-fluorescence (EDIC/EF), microscopy has been used successfully to visualise the 3-D biofilm structure, physiological niches, protozoal grazing and iron biomineralization, and the location of specific pathogens such as Legionella pneumophila, Campylobacter jejuni and Cryptosporidium parvum. These species were identified using gold nanoparticles or fluorophores coupled to monoclonal antibodies or 16S rRNA probes, respectively. Among its many potential uses, the EDIC technique will provide a rapid procedure to facilitate the calibration of the modern generation of biofilm-sensing electrodes.

Highly dynamic animal contact network and implications on disease transmission

PubMed Central

Chen, Shi; White, Brad J.; Sanderson, Michael W.; Amrine, David E.; Ilany, Amiyaal; Lanzas, Cristina

2014-01-01

Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R0 < 2). PMID:24667241

Effects of triclosan on bacterial community composition and ...

EPA Pesticide Factsheets

Pharmaceuticals and personal care products, including antimicrobials, can be found at trace levels in treated wastewater effluent. Impacts of chemical contaminants on coastal aquatic microbial community structure and pathogen abundance are unknown despite the potential for selection through antimicrobial resistance. In particular, Vibrio, a marine bacterial genus that includes several human pathogens, displays resistance to the ubiquitous antimicrobial compound triclosan. Here we demonstrated through use of natural seawater microcosms that triclosan (at a concentration of ~5 ppm) can induce a significant Vibrio growth response (68–1,700 fold increases) in comparison with no treatment controls for three distinct coastal ecosystems: Looe Key Reef (Florida Keys National Marine Sanctuary), Doctors Arm Canal (Big Pine Key, FL), and Clam Bank Landing (North Inlet Estuary, Georgetown, SC). Additionally, microbial community analysis by 16 S rRNA gene sequencing for Looe Key Reef showed distinct changes in microbial community structure with exposure to 5 ppm triclosan, with increases observed in the relative abundance of Vibrionaceae (17-fold), Pseudoalteromonadaceae (65-fold), Alteromonadaceae (108-fold), Colwelliaceae (430-fold), and Oceanospirillaceae (1,494-fold). While the triclosan doses tested were above concentrations typically observed in coastal surface waters, results identify bacterial families that are potentially resistant to triclosan and/or adapted to u

Spatial variation in disease resistance: from molecules to metapopulations

PubMed Central

Laine, Anna-Liisa; Burdon, Jeremy J.; Dodds, Peter N.; Thrall, Peter H.

2010-01-01

Summary Variation in disease resistance is a widespread phenomenon in wild plant-pathogen associations. Here, we review current literature on natural plant-pathogen associations to determine how diversity in disease resistance is distributed at different hierarchical levels – within host individuals, within host populations, among host populations at the metapopulation scale and at larger regional scales. We find diversity in resistance across all spatial scales examined. Furthermore, variability seems to be the best counter-defence of plants against their rapidly evolving pathogens. We find that higher diversity of resistance phenotypes also results in higher levels of resistance at the population level. Overall, we find that wild plant populations are more likely to be susceptible than resistant to their pathogens. However, the degree of resistance differs strikingly depending on the origin of the pathogen strains used in experimental inoculation studies. Plant populations are on average 16% more resistant to allopatric pathogen strains than they are to strains that occur within the same population (48 % vs. 32 % respectively). Pathogen dispersal mode affects levels of resistance in natural plant populations with lowest levels detected for hosts of airborne pathogens and highest for waterborne pathogens. Detailed analysis of two model systems, Linum marginale infected by Melampsora lini, and Plantago lanceolata infected by Podosphaera plantaginis, show that the amount of variation in disease resistance declines towards higher spatial scales as we move from individual hosts to metapopulations, but evaluation of multiple spatial scales is needed to fully capture the structure of disease resistance. Synthesis: Variation in disease resistance is ubiquitous in wild plant-pathogen associations. While the debate over whether the resistance structure of plant populations is determined by pathogen-imposed selection versus non-adaptive processes remains unresolved, we do report examples of pathogen-imposed selection on host resistance. Here we highlight the importance of measuring resistance across multiple spatial scales, and of using sympatric strains when looking for signs of coevolution in wild plant-pathogen interactions. PMID:21243068

Influence of manure age and sunlight on the community structure of cattle fecal bacteria as revealed by Illumina sequencing

NASA Astrophysics Data System (ADS)

Wong, K.; Shaw, T. I.; Oladeinde, A.; Molina, M.

2013-12-01

Fecal pollution of environmental waters is a major concern for the general public because exposure to fecal-associated pathogens can have severe impacts on human health. Stream and river impairment due to fecal pollution is largely the result of agricultural activities in the United States. In the last few years, numerous metagenomic studies utilized next generation sequencing to develop microbial community profiles by massively sequencing the 16sRNA hypervariable region. This technology supports the application of water quality assessment such as pathogen detection and fecal source tracking. The bacteria communities of samples in these studies were determined when they were freshly collected; therefore, little is known about how feces age or how environmental stress influences the microbial ecology of fecal materials. In this study we monitored bacteria community changes in cattle feces for 57 days after excretion (day 0, 2, 4 8, 15, 22, 29, 43, 57) by sequencing the 16s variable region 4, using Illumnia MiSeq. Twelve cattle feces were studied; half of the samples were directly exposed to sunlight (unshaded) and half were shaded. Results indicate that the relative abundance (RA) profile in both shaded and unshaded samples rapidly changed from day 0 to 15, but stabilized from day 22 to 57. Firmcutes were the most abundant phylum (~40%) at day 0, but were reduced to <10% by day 57. The RA of Proteobacteria was only 1% at day 0, but increased to ~50% by day 57in both shaded and unshaded samples. By the end of the study, shaded and unshaded samples had a similar RA of Firmcutes and Proteobacteria but the RA of Bacteroidetes and Actinobacteria was, respectively, about 7% lower and 10% higher for unshaded samples. UV intensity, moisture, and temperature were significantly different between shaded and unshaded plots, indicating that these environmental stresses could influence the structure of fecal bacteria community in the natural environment. According to the rarefaction curve analysis, richness of bacteria diversity in feces decreased as time progressed. Some pathogens such as Campylobacter were detected only at the beginning, meaning they substantially decayed during the course of our study. Overall, this study indicated: (1) sunlight can influence the community structure and (2) after excretion the fecal bacteria diversity can be significantly changed over time. Future studies should therefore use not only the microbial signature of fresh but also moderately aged fecal samples to develop more accurate community profiles for fecal source tracking.

A Spectral Mapping Signature for the Rapid Ohia Death (ROD) Pathogen in Hawaiian Forests

USDA-ARS?s Scientific Manuscript database

Pathogenic invasions are a major disruptive source of change in both agricultural and natural ecosystems. In forests, fungal pathogens can kill habitat-generating plant species such as canopy trees, but methods for remote detection, mapping and monitoring of such outbreaks are poorly developed. Cera...

ARE THERE PATHOGENS IN YOUR SEWAGE SLUDGE? CHANGING APPROAHCES TO CONTROLLING PATHOGENS IN SEWAGE SLUDGE AND THEIR VECTOR ATTRACTIVENESS.

EPA Science Inventory

This presentation will review the commonly employed Class A & B processes for controlling pathogens; note how extensively they are used; and discuss issues and concerns. Processes presently being researched will also be noted together with EPA's methodology for determining equiva...

Risks Posed by Reston, the Forgotten Ebolavirus

PubMed Central

Cantoni, Diego; Hamlet, Arran; Michaelis, Martin; Wass, Mark N.

2016-01-01

ABSTRACT Out of the five members of the Ebolavirus family, four cause life-threatening disease, whereas the fifth, Reston virus (RESTV), is nonpathogenic in humans. The reasons for this discrepancy remain unclear. In this review, we analyze the currently available information to provide a state-of-the-art summary of the factors that determine the human pathogenicity of Ebolaviruses. RESTV causes sporadic infections in cynomolgus monkeys and is found in domestic pigs throughout the Philippines and China. Phylogenetic analyses revealed that RESTV is most closely related to the Sudan virus, which causes a high mortality rate in humans. Amino acid sequence differences between RESTV and the other Ebolaviruses are found in all nine Ebolavirus proteins, though no one residue appears sufficient to confer pathogenicity. Changes in the glycoprotein contribute to differences in Ebolavirus pathogenicity but are not sufficient to confer pathogenicity on their own. Similarly, differences in VP24 and VP35 affect viral immune evasion and are associated with changes in human pathogenicity. A recent in silico analysis systematically determined the functional consequences of sequence variations between RESTV and human-pathogenic Ebolaviruses. Multiple positions in VP24 were differently conserved between RESTV and the other Ebolaviruses and may alter human pathogenicity. In conclusion, the factors that determine the pathogenicity of Ebolaviruses in humans remain insufficiently understood. An improved understanding of these pathogenicity-determining factors is of crucial importance for disease prevention and for the early detection of emergent and potentially human-pathogenic RESTVs. PMID:28066813

Functional diversification of structurally alike NLR proteins in plants.

PubMed

Chakraborty, Joydeep; Jain, Akansha; Mukherjee, Dibya; Ghosh, Suchismita; Das, Sampa

2018-04-01

In due course of evolution many pathogens alter their effector molecules to modulate the host plants' metabolism and immune responses triggered upon proper recognition by the intracellular nucleotide-binding oligomerization domain containing leucine-rich repeat (NLR) proteins. Likewise, host plants have also evolved with diversified NLR proteins as a survival strategy to win the battle against pathogen invasion. NLR protein indeed detects pathogen derived effector proteins leading to the activation of defense responses associated with programmed cell death (PCD). In this interactive process, genome structure and plasticity play pivotal role in the development of innate immunity. Despite being quite conserved with similar biological functions in all eukaryotes, the intracellular NLR immune receptor proteins happen to be structurally distinct. Recent studies have made progress in identifying transcriptional regulatory complexes activated by NLR proteins. In this review, we attempt to decipher the intracellular NLR proteins mediated surveillance across the evolutionarily diverse taxa, highlighting some of the recent updates on NLR protein compartmentalization, molecular interactions before and after activation along with insights into the finer role of these receptor proteins to combat invading pathogens upon their recognition. Latest information on NLR sensors, helpers and NLR proteins with integrated domains in the context of plant pathogen interactions are also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Coexistence and specialization of pathogen strains on contact networks.

PubMed

Eames, Ken T D; Keeling, Matt J

2006-08-01

The coexistence of different pathogen strains has implications for pathogen variability and disease control and has been explained in a number of different ways. We use contact networks, which represent interactions between individuals through which infection could be transmitted, to investigate strain coexistence. For sexually transmitted diseases the structure of contact networks has received detailed study and has been shown to be a vital determinant of the epidemiological dynamics. By using analytical pairwise models and stochastic simulations, we demonstrate that network structure also has a profound influence on the interaction between pathogen strains. In particular, when the population is serially monogamous, fully cross-reactive strains can coexist, with different strains dominating in network regions with different characteristics. Furthermore, we observe specialization of different strains in different risk groups within the network, suggesting the existence of diverging evolutionary pressures.

Seasonal variation in the biocontrol efficiency of bacterial wilt is driven by temperature-mediated changes in bacterial competitive interactions.

PubMed

Wei, Zhong; Huang, Jianfeng; Yang, Tianjie; Jousset, Alexandre; Xu, Yangchun; Shen, Qirong; Friman, Ville-Petri

2017-10-01

Microbe-based biocontrol applications hold the potential to become an efficient way to control plant pathogen disease outbreaks in the future. However, their efficiency is still very variable, which could be due to their sensitivity to the abiotic environmental conditions.Here, we assessed how environmental temperature variation correlates with ability of Ralstonia pickettii , an endophytic bacterial biocontrol agent, to suppress the Ralstonia solanacearum pathogen during different tomato crop seasons in China.We found that suppression of the pathogen was highest when the seasonal mean temperatures were around 20 °C and rapidly decreased with increasing mean crop season temperatures. Interestingly, low levels of disease incidence did not correlate with low pathogen or high biocontrol agent absolute densities. Instead, the biocontrol to pathogen density ratio was a more important predictor of disease incidence levels between different crop seasons. To understand this mechanistically, we measured the growth and strength of competition between the biocontrol agent and the pathogen over a naturally occurring temperature gradient in vitro . We found that the biocontrol strain grew relatively faster at low temperature ranges, and the pathogen at high temperature ranges, and that similar to field experiments, pathogen suppression peaked at 20 °C.Together, our results suggest that temperature-mediated changes in the strength of bacterial competition could potentially explain the variable R. solanacearum biocontrol outcomes between different crop seasons in China. Synthesis and applications . Our results suggest that abiotic environmental conditions, such as temperature, can affect the efficacy of biocontrol applications. Thus, in order to develop more consistent biocontrol applications in the future, we might need to find and isolate bacterial strains that can retain their functionality regardless of the changing environmental conditions.

[Effects of grape-replanting on soil bacterial and fungal populations].

PubMed

Li, Kun; Guo, Xiu-wu; Sun, Ying-ni; Zhang, Li-heng; Hu, Xi-xi

2009-12-01

Rhizosphere and non-rhizosphere soil samples were collected from the vineyards having been planted for 3 and 30 years, and PCR-DGGE technique was adopted to study the effects of grape-replanting on the population structure and diversity of soil bacteria and fungi. The bacterial and fungal diversities were higher in 30-year-planted vineyard than in 3-year-planted vineyard, and higher in rhizosphere soil than in non-rhizosphere soil. After 30 years replanting, the population structure of bacteria and fungi approached the same in rhizosphere soil and non-rhizosphere soil but differed from that in fallow soil; while in the 3-year-planted vineyard, the population structure in rhizosphere soil was different from that in non-rhizosphere soil and fallow soil. Comparing with that in 3-year-planted vineyard, the rhizosphere soil microbial population in 30-year-planted vineyard had a greater change. In bacterial population, Flavobacterium sp. (DQ339585) and Bacillus sp. (AY039821) decreased while Pedobacter sp. (AJ871084) increased; in fungal population, Omphalina farinolens (EF413029) appeared, Pestalotiopsis sp. (DQ657877, DQ657875, DQ657871), Phacidium lacerum (DQ470976), and Lecythophora decumbens (AF353597) decreased, while Pilidium acerinum voucher (AY48709) increased. Bacillus sp., Flavobacterium sp. , and Pestalotiopsis sp. had antagonism to pathogen, and their decrease reduced the resistance of grape against pathogen. The increase of Pilidium acerinum voucher might relate to the severe disease after grape-replanting.

Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta

PubMed Central

Jia, Mingrui; Shi, Ranran; Zhao, Xuli; Fu, Zhijian; Bai, Zhijing; Sun, Tao; Zhao, Xuejun; Wang, Wenbo; Xu, Chao; Yan, Fang

2017-01-01

Abstract Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation. A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis. The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen. We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen. PMID:28953610

Woodland structure affects intensity of infection by an exotic forest pathogen

Treesearch

Nathan Rank; Hall Cushman; Ross Meentemeyer

2008-01-01

Woodland ecosystems often consist of a mosaic of interacting dominant woody species that vary in density and abundance. Local variation in dominant species abundance may influence spread of plant pathogens across this heterogeneous landscape. We investigated this possibility in a 275 km2 study area in eastern Sonoma County, which is being invaded by the pathogen that...

Insights from molecular modeling and dynamics simulation of pathogen resistance (R) protein from brinjal.

PubMed

Shrivastava, Dipty; Nain, Vikrant; Sahi, Shakti; Verma, Anju; Sharma, Priyanka; Sharma, Prakash Chand; Kumar, Polumetla Ananda

2011-01-22

Resistance (R) protein recognizes molecular signature of pathogen infection and activates downstream hypersensitive response signalling in plants. R protein works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study is aimed at predicting structure of R proteins signalling domains (CC-NBS) by creating a homology model, refining and optimising the model by molecular dynamics simulation and comparing ADP and ATP binding. Based on sequence similarity with proteins of known structures, CC-NBS domains were initially modelled using CED- 4 (cell death abnormality protein) and APAF-1 (apoptotic protease activating factor) as multiple templates. The final CC-NBS structural model was built and optimized by molecular dynamic simulation for 5 nanoseconds (ns). Docking of ADP and ATP at active site shows that both ligand bind specifically with same residues and with minor difference (1 Kcal/mol) in binding energy. Sharing of binding site by ADP and ATP and low difference in their binding site makes CC-NBS suitable for working as molecular switch. Furthermore, structural superimposition elucidate that CC-NBS and CARD (caspase recruitment domains) domain of CED-4 have low RMSD value of 0.9 A° Availability of 3D structural model for both CC and NBS domains will . help in getting deeper insight in these pathogen defence genes.

Spatial evolutionary epidemiology of spreading epidemics

PubMed Central

2016-01-01

Most spatial models of host–parasite interactions either neglect the possibility of pathogen evolution or consider that this process is slow enough for epidemiological dynamics to reach an equilibrium on a fast timescale. Here, we propose a novel approach to jointly model the epidemiological and evolutionary dynamics of spatially structured host and pathogen populations. Starting from a multi-strain epidemiological model, we use a combination of spatial moment equations and quantitative genetics to analyse the dynamics of mean transmission and virulence in the population. A key insight of our approach is that, even in the absence of long-term evolutionary consequences, spatial structure can affect the short-term evolution of pathogens because of the build-up of spatial differentiation in mean virulence. We show that spatial differentiation is driven by a balance between epidemiological and genetic effects, and this quantity is related to the effect of kin competition discussed in previous studies of parasite evolution in spatially structured host populations. Our analysis can be used to understand and predict the transient evolutionary dynamics of pathogens and the emergence of spatial patterns of phenotypic variation. PMID:27798295

Spatial evolutionary epidemiology of spreading epidemics.

PubMed

Lion, S; Gandon, S

2016-10-26

Most spatial models of host-parasite interactions either neglect the possibility of pathogen evolution or consider that this process is slow enough for epidemiological dynamics to reach an equilibrium on a fast timescale. Here, we propose a novel approach to jointly model the epidemiological and evolutionary dynamics of spatially structured host and pathogen populations. Starting from a multi-strain epidemiological model, we use a combination of spatial moment equations and quantitative genetics to analyse the dynamics of mean transmission and virulence in the population. A key insight of our approach is that, even in the absence of long-term evolutionary consequences, spatial structure can affect the short-term evolution of pathogens because of the build-up of spatial differentiation in mean virulence. We show that spatial differentiation is driven by a balance between epidemiological and genetic effects, and this quantity is related to the effect of kin competition discussed in previous studies of parasite evolution in spatially structured host populations. Our analysis can be used to understand and predict the transient evolutionary dynamics of pathogens and the emergence of spatial patterns of phenotypic variation. © 2016 The Author(s).

[Comparative analysis of structural changes in thrombocytes during Alzheimer's and Parkinson's diseases].

PubMed

Simonidze, V; Samushia, O

2014-01-01

The paper deals with the study of the changes in the formed elements of blood during the Alzheimer's and Parkinson's diseases. While studying the structure of thrombocytes, a number of identical structural changes were identified in case of both diseases. The study has revealed various shapes of thrombocytes, the production of pseudopodia on their surface, high level of body outline, specific distribution of glycogen granules and their concentration on the periphery, glycogen eruption, dissociation of Alpha-granules towards the edge, and effective outline and density of the granules. There are frequent cases of the granule eruption from the body (exocytosis), the existence of vacuoles on the matrix, the rise in the number of gigantic thrombocytes and, consequently, considerable enhancement of the ability of absorption. Besides, there is a rise in the number of degenerated cells. The shape of thrombocytes is often changed and stretched on one side. The produced pseudopodia make the impression of participation in phagocytosis. As for the difference between changes, during Parkinson disease the amount of thrombocytes is low, more gigantic and distorted shape, less invagination of plasma membrane, low amount of granules and less intensity of alpha-granule eruption from the body. The changes revealed by the research show the activity of thrombocytes, which should be connected to their participation in protective functions of the body towards existing agent. And the diseases - although with similar but with different pathogenic mechanisms - are being developed with participation of non-specific agents.

Molecular Epidemiology and Genomics of Group A Streptococcus

PubMed Central

Bessen, Debra E.; McShan, W. Michael; Nguyen, Scott V.; Shetty, Amol; Agrawal, Sonia; Tettelin, Hervé

2014-01-01

Streptococcus pyogenes (group A streptococcus; GAS) is a strict human pathogen with a very high prevalence worldwide. This review highlights the genetic organization of the species and the important ecological considerations that impact its evolution. Recent advances are presented on the topics of molecular epidemiology, population biology, molecular basis for genetic change, genome structure and genetic flux, phylogenomics and closely related streptococcal species, and the long- and short-term evolution of GAS. The application of whole genome sequence data to addressing key biological questions is discussed. PMID:25460818

The diversity and prevalence of hard ticks attacking human hosts in Eastern Siberia (Russian Federation) with first description of invasion of non-endemic tick species.

PubMed

Khasnatinov, Maxim Anatolyevich; Liapunov, Alexander Valeryevich; Manzarova, Ellina Lopsonovna; Kulakova, Nina Viktorovna; Petrova, Irina Viktorovna; Danchinova, Galina Anatolyevna

2016-02-01

Hard ticks are the vectors of many pathogens including tick-borne encephalitis virus and the Lyme disease agent Borrelia burgdorferi sensu lato. In Eastern Siberia, Ixodes persulcatus, Dermacentor nuttalli, Dermacentor silvarum and Haemaphysalis concinna are regarded as aggressive to humans. Recently, significant changes in world tick fauna have been reported and this affects the spread of tick-borne pathogens. We studied the current species diversity, population structure and prevalence of tick-borne pathogens of hard ticks (Acari: Ixodidae) that attacked humans in Eastern Siberia (Irkutsk region, Russia). In total, 31,892 individual ticks were identified and analysed during the years 2007-2014. The majority (85.4%) of victims was bitten by I. persulcatus, 14.55% of attacks on humans were caused by D. nuttalli and D. silvarum, whereas H. concinna was documented only in 15 cases (0.05%). The seasonal activity and the age/gender structure of the tick population were studied as well. Among all the studied ticks, three unconventional species, i.e. Rhipicephalus sanguineus, Dermacentor reticulatus and Amblyomma americanum, were identified. Analysis of tick bite histories indicates at least three events of invasion of non-endemic ticks into the ecosystems of northern Eurasia with harsh continental climates. Invading ticks are able to reach the adult life stage and are aggressive to the local human population. Phylogenetic analysis of mt 16S rRNA gene fragments suggests multiple independent routes of tick migration to Eastern Siberia. Possible implications to human health and epidemiology of tick-borne infections are discussed.

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

USDA-ARS?s Scientific Manuscript database

The Asian citrus psyllid (Diaphorina citri) is the insect vector responsible for the worldwide spread of Candidatus Liberibacter asiaticus, the bacterial pathogen associated with citrus greening disease. Developmental changes in the insect vector impact pathogen transmission, such that D. citri tra...

Food safety trends in the U.S. and update on pathogenic E. coli

USDA-ARS?s Scientific Manuscript database

Foodborne Diseases Active Surveillance Network (FoodNet): FoodNet is a main part of the Centers for Disease Control and Prevention’s (CDC) Emerging Pathogens Program and was established in 1995 as a population-based sentinel surveillance system to monitor changes in the incidence of nine pathogens ...

Analyses of natural variation indicates that the absence of RPS4/RRS1 and amino acid change in RPS4 cause loss of their functions and resistance to pathogens.

PubMed

Narusaka, Mari; Iuchi, Satoshi; Narusaka, Yoshihiro

2017-03-04

A pair of Arabidopsis thaliana resistance proteins, RPS4 and RRS1, recognizes the cognate Avr effector from the bacterial pathogens Pseudomonas syringae pv. tomato expressing avrRps4 (Pst-avrRps4), Ralstonia solanacearum, and the fungal pathogen Colletotrichum higginsianum and leads to defense signaling activation against the pathogens. In the present study, we analyzed 14 A. thaliana accessions for natural variation in Pst-avrRps4 and C. higginsianum susceptibility, and found new compatible and incompatible Arabidopsis-pathogen interactions. We first found that A. thaliana accession Cvi-0 is susceptible to Pst-avrRps4. Interestingly, the genome sequence assembly indicated that Cvi-0 lost both RPS4 and RRS1, but not RPS4B and RRS1B, compared to the reference genome sequence from A. thaliana accession Col-0. On the other hand, the natural variation analysis of RPS4 alleles from various Arabidopsis accessions revealed that one amino-acid change, Y950H, is responsible for the loss of resistance to Pst-avrRps4 and C. higginsianum in RLD-0. Our data indicate that the amino acid change, Y950H, in RPS4 resulted in the loss of both RPS4 and RRS1 functions and resistance to pathogens.

Sensitive-cell-based fish chromatophore biosensor

NASA Astrophysics Data System (ADS)

Plant, Thomas K.; Chaplen, Frank W.; Jovanovic, Goran; Kolodziej, Wojtek; Trempy, Janine E.; Willard, Corwin; Liburdy, James A.; Pence, Deborah V.; Paul, Brian K.

2004-07-01

A sensitive biosensor (cytosensor) has been developed based on color changes in the toxin-sensitive colored living cells of fish. These chromatophores are highly sensitive to the presence of many known and unknown toxins produced by microbial pathogens and undergo visible color changes in a dose-dependent manner. The chromatophores are immobilized and maintained in a viable state while potential pathogens multiply and fish cell-microbe interactions are monitored. Low power LED lighting is used to illuminate the chromatophores which are magnified using standard optical lenses and imaged onto a CCD array. Reaction to toxins is detected by observing changes is the total area of color in the cells. These fish chromatophores are quite sensitive to cholera toxin, Staphococcus alpha toxin, and Bordatella pertussis toxin. Numerous other toxic chemical and biological agents besides bacterial toxins also cause readily detectable color effects in chromatophores. The ability of the chromatophore cell-based biosensor to distinguish between different bacterial pathogens was examined. Toxin producing strains of Salmonella enteritis, Vibrio parahaemolyticus, and Bacillus cereus induced movement of pigmented organelles in the chromatophore cells and this movement was measured by changes in the optical density over time. Each bacterial pathogen elicited this measurable response in a distinctive and signature fashion. These results suggest a chromatophore cell-based biosensor assay may be applicable for the detection and identification of virulence activities associated with certain air-, food-, and water-borne bacterial pathogens.

Structure of the OsSERK2 leucine-rich repeat extracellular domain.

PubMed

McAndrew, Ryan; Pruitt, Rory N; Kamita, Shizuo G; Pereira, Jose Henrique; Majumdar, Dipali; Hammock, Bruce D; Adams, Paul D; Ronald, Pamela C

2014-11-01

Somatic embryogenesis receptor kinases (SERKs) are leucine-rich repeat (LRR)-containing integral membrane receptors that are involved in the regulation of development and immune responses in plants. It has recently been shown that rice SERK2 (OsSERK2) is essential for XA21-mediated resistance to the pathogen Xanthomonas oryzae pv. oryzae. OsSERK2 is also required for the BRI1-mediated, FLS2-mediated and EFR-mediated responses to brassinosteroids, flagellin and elongation factor Tu (EF-Tu), respectively. Here, crystal structures of the LRR domains of OsSERK2 and a D128N OsSERK2 mutant, expressed as hagfish variable lymphocyte receptor (VLR) fusions, are reported. These structures suggest that the aspartate mutation does not generate any significant conformational change in the protein, but instead leads to an altered interaction with partner receptors.

Projecting the global distribution of the emerging amphibian fungal pathogen, batrachochytrium dendrobatidis, based on IPCC climate futures

Treesearch

Gisselle Yang Xie; Deanna H. Olson; Andrew R. Blaustein

2016-01-01

Projected changes in climate conditions are emerging as significant risk factors to numerous species, affecting habitat conditions and community interactions. Projections suggest species range shifts in response to climate change modifying environmental suitability and is supported by observational evidence. Both pathogens and their hosts can shift ranges with climate...

The spread of invasive species and infectious disease as drivers of ecosystem change.

Treesearch

Todd A. Crowl; Thomas O. Crist; Robert R. Parmenter; Gary Belovsky; Ariel E. Lugo

2008-01-01

Invasive species, disease vectors, and pathogens affect biodiversity, ecosystem function and services, and human health. Climate change, land use, and transport vectors interact in complex ways to determine the spread of native and non-native invasive species, pathogens, and their effects on ecosystem dynamics. Early detection and in-depth understanding of invasive...

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...

Raman characterization of Avocado Sunblotch viroid and its response to external perturbations and self-cleavage

PubMed Central

2014-01-01

Background Viroids are the smallest pathogens of plants. To date the structural and conformational details of the cleavage of Avocado sunblotch viroid (ASBVd) and the catalytic role of Mg2+ ions in efficient self-cleavage are of crucial interest. Results We report the first Raman characterization of the structure and activity of ASBVd, for plus and minus viroid strands. Both strands exhibit a typical A-type RNA conformation with an ordered double-helical content and a C3′-endo/anti sugar pucker configuration, although small but specific differences are found in the sugar puckering and base-stacking regions. The ASBVd(-) is shown to self-cleave 3.5 times more actively than ASBVd(+). Deuteration and temperature increase perturb differently the double-helical content and the phosphodiester conformation, as revealed by corresponding characteristic Raman spectral changes. Our data suggest that the structure rigidity and stability are higher and the D2O accessibility to H-bonding network is lower for ASBVd(+) than for ASBVd(-). Remarkably, the Mg2+-activated self-cleavage of the viroid does not induce any significant alterations of the secondary viroid structure, as evidenced from the absence of intensity changes of Raman marker bands that, however exhibit small but noticeable frequency downshifts suggesting several minor changes in phosphodioxy, internal loops and hairpins of the cleaved viroids. Conclusions Our results demonstrate the sensitivity of Raman spectroscopy in monitoring structural and conformational changes of the viroid and constitute the basis for further studies of its interactions with therapeutic agents and cell membranes. PMID:24655924

Structural engineering of a phage lysin that targets Gram-negative pathogens

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

Lukacik, Petra; Barnard, Travis J.; Keller, Paul W.

Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against Gram-positive organisms but not against Gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a {beta}-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and anothermore » that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora.« less

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.

Extensive Metabolic Remodeling Differentiates Non-pathogenic and Pathogenic Growth Forms of the Dimorphic Pathogen Talaromyces marneffei

PubMed Central

Pasricha, Shivani; MacRae, James I.; Chua, Hwa H.; Chambers, Jenny; Boyce, Kylie J.; McConville, Malcolm J.; Andrianopoulos, Alex

2017-01-01

Fungal infections are an increasing public health problem, particularly in immunocompromised individuals. While these pathogenic fungi show polyphyletic origins with closely related non-pathogenic species, many undergo morphological transitions to produce pathogenic cell types that are associated with increased virulence. However, the characteristics of these pathogenic cells that contribute to virulence are poorly defined. Talaromyces marneffei grows as a non-pathogenic hyphal form at 25°C but undergoes a dimorphic transition to a pathogenic yeast form at 37°C in vitro and following inhalation of asexual conidia by a host. Here we show that this transition is associated with major changes in central carbon metabolism, and that these changes are correlated with increased virulence of the yeast form. Comprehensive metabolite profiling and 13C-labeling studies showed that hyphal cells exhibited very active glycolytic metabolism and contain low levels of internal carbohydrate reserves. In contrast, yeast cells fully catabolized glucose in the mitochondrial TCA cycle, and store excess glucose in large intracellular pools of trehalose and mannitol. Inhibition of the yeast TCA cycle inhibited replication in culture and in host cells. Yeast, but not hyphae, were also able to use myo-inositol and amino acids as secondary carbon sources, which may support their survival in host macrophages. These analyses suggest that T. marneffei yeast cells exhibit a more efficient oxidative metabolism and are capable of utilizing a diverse range of carbon sources, which contributes to their virulence in animal tissues, highlighting the importance of dimorphic switching in pathogenic yeast. PMID:28861398

Extensive Metabolic Remodeling Differentiates Non-pathogenic and Pathogenic Growth Forms of the Dimorphic Pathogen Talaromyces marneffei.

PubMed

Pasricha, Shivani; MacRae, James I; Chua, Hwa H; Chambers, Jenny; Boyce, Kylie J; McConville, Malcolm J; Andrianopoulos, Alex

2017-01-01

Fungal infections are an increasing public health problem, particularly in immunocompromised individuals. While these pathogenic fungi show polyphyletic origins with closely related non-pathogenic species, many undergo morphological transitions to produce pathogenic cell types that are associated with increased virulence. However, the characteristics of these pathogenic cells that contribute to virulence are poorly defined. Talaromyces marneffei grows as a non-pathogenic hyphal form at 25°C but undergoes a dimorphic transition to a pathogenic yeast form at 37°C in vitro and following inhalation of asexual conidia by a host. Here we show that this transition is associated with major changes in central carbon metabolism, and that these changes are correlated with increased virulence of the yeast form. Comprehensive metabolite profiling and 13 C-labeling studies showed that hyphal cells exhibited very active glycolytic metabolism and contain low levels of internal carbohydrate reserves. In contrast, yeast cells fully catabolized glucose in the mitochondrial TCA cycle, and store excess glucose in large intracellular pools of trehalose and mannitol. Inhibition of the yeast TCA cycle inhibited replication in culture and in host cells. Yeast, but not hyphae, were also able to use myo -inositol and amino acids as secondary carbon sources, which may support their survival in host macrophages. These analyses suggest that T. marneffei yeast cells exhibit a more efficient oxidative metabolism and are capable of utilizing a diverse range of carbon sources, which contributes to their virulence in animal tissues, highlighting the importance of dimorphic switching in pathogenic yeast.

Manipulation of host membranes by the bacterial pathogens Listeria, Francisella, Shigella and Yersinia.

PubMed

Pizarro-Cerdá, Javier; Charbit, Alain; Enninga, Jost; Lafont, Frank; Cossart, Pascale

2016-12-01

Bacterial pathogens display an impressive arsenal of molecular mechanisms that allow survival in diverse host niches. Subversion of plasma membrane and cytoskeletal functions are common themes associated to infection by both extracellular and intracellular pathogens. Moreover, intracellular pathogens modify the structure/stability of their membrane-bound compartments and escape degradation from phagocytic or autophagic pathways. Here, we review the manipulation of host membranes by Listeria monocytogenes, Francisella tularensis, Shigella flexneri and Yersinia spp. These four bacterial model pathogens exemplify generalized strategies as well as specific features observed during bacterial infection processes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gene-for-gene disease resistance: bridging insect pest and pathogen defense.

PubMed

Kaloshian, Isgouhi

2004-12-01

Active plant defense, also known as gene-for-gene resistance, is triggered when a plant resistance (R) gene recognizes the intrusion of a specific insect pest or pathogen. Activation of plant defense includes an array of physiological and transcriptional reprogramming. During the past decade, a large number of plant R genes that confer resistance to diverse group of pathogens have been cloned from a number of plant species. Based on predicted protein structures, these genes are classified into a small number of groups, indicating that structurally related R genes recognize phylogenetically distinct pathogens. An extreme example is the tomato Mi-1 gene, which confers resistance to potato aphid (Macrosiphum euphorbiae), whitefly (Bemisia tabaci), and root-knot nematodes (Meloidogyne spp.). While Mi-1 remains the only cloned insect R gene, there is evidence that gene-for-gene type of plant defense against piercing-sucking insects exists in a number of plant species.

Exploring the molecular mechanisms of parasite-host interactions with a view towards new therapeutics and vaccines.

PubMed

Cross, Megan; Klepzig, Emma; Dallaston, Madeleine; Young, Neil D; Bailey, Ulla-Maja; Mason, Lyndel; Jones, Malcolm K; Gasser, Robin B; Hofmann, Andreas

Despite the massive disease burden worldwide caused by parasitic nematodes and other infectious pathogens, the molecular basis of many infectious diseases caused by these pathogens has been unduly neglected for a long time. Therefore, accelerated progress towards novel therapeutics, and ultimately control of such infectious diseases, is of crucial importance. Capitalising on the wealth of data becoming available from proteomic and genomic studies, new protein targets at the pathogen-host interface can be identified and subjected to protein-based explorations of the molecular basis of pathogen-host interactions. By combining the use of systems and structural biology methodologies, insights into the structural and molecular mechanisms of these interactions can assist in the development of therapeutics and/or vaccines. This brief review examines two different proteins from the body wall of blood flukes - annexins and the stress-induced phosphoprotein 1 - both of which are presently interesting targets for the development of therapeutics.

Portrait of an Enzyme, a Complete Structural Analysis of a Multimodular beta-N-Acetylglucosaminidase from Clostridium perfringens

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

Ficko-Blean, E.; Gregg, K; Adams, J

2009-01-01

Common features of the extracellular carbohydrate-active virulence factors involved in host-pathogen interactions are their large sizes and modular complexities. This has made them recalcitrant to structural analysis, and therefore our understanding of the significance of modularity in these important proteins is lagging. Clostridium perfringens is a prevalent human pathogen that harbors a wide array of large, extracellular carbohydrate-active enzymes and is an excellent and relevant model system to approach this problem. Here we describe the complete structure of C. perfringens GH84C (NagJ), a 1001-amino acid multimodular homolog of the C. perfringens ?-toxin, which was determined using a combination of smallmore » angle x-ray scattering and x-ray crystallography. The resulting structure reveals unprecedented insight into how catalysis, carbohydrate-specific adherence, and the formation of molecular complexes with other enzymes via an ultra-tight protein-protein interaction are spatially coordinated in an enzyme involved in a host-pathogen interaction.« less

Canopy gaps decrease microbial densities and disease risk for a shade-intolerant tree species

NASA Astrophysics Data System (ADS)

Reinhart, Kurt O.; Royo, Alejandro A.; Kageyama, Stacie A.; Clay, Keith

2010-11-01

Canopy disturbances such as windthrow events have obvious impacts on forest structure and composition aboveground, but changes in soil microbial communities and the consequences of these changes are less understood. We characterized the densities of a soil-borne pathogenic oomycete ( Pythium) and a common saprotrophic zygomycete ( Mortierella) in nine pairs of forest gaps created by windthrows and adjacent forest understories. We determined the levels of Pythium necessary to cause disease by performing pathogenicity experiments using two Pythium species, a range of Pythium densities, and two common tree species ( Acer rubrum and Prunus serotina) from the study sites. Three years post-disturbance, densities of Mortierella remained suppressed in soil from forest gaps compared to levels in intact forest understories while varying across sites and sampling dates. Pythium were infrequently detected likely because of soil handling effects. Expression of disease symptoms increased with increasing inoculum density for seedlings of P. serotina with each Pythium spp. having a similar effect on this species. Conversely, A. rubrum appeared resistant to the two species of Pythium. These results suggest that Pythium densities at sites where they were detected are sufficient to cause disease and possibly affect establishment of susceptible species like P. serotina. Because early seral environments have lower loads of the saprotrophic Mortierella, pathogen loads may follow a similar pattern, causing susceptible species to establish more frequently in those habitats than in late-seral forests. Forest disturbances that alter the disease landscape may provide an additional mechanism for explaining succession of temperate forests in addition to the shade-tolerance paradigm.

Pathogen characteristics reveal novel antibacterial approaches for interstitial lung disease.

PubMed

Lu, Hai-Wen; Ji, Xiao-Bin; Liang, Shuo; Fan, Li-Chao; Bai, Jiu-Wu; Chen, Ke-Bing; Zhou, Yin; Li, Hui-Ping; Xu, Jin-Fu

2014-12-01

Interstitial lung disease (ILD) is a clinical disorder associated with changes of lung structure. Concurrent infection is a serious complication and one of the major factors that exacerbates ILD. Pathogen screening is a critical step in early diagnosis and proper treatment of ILD with secondary infection. Here we analyzed distribution and drug susceptibility of pathogens isolated from hospitalized ILD patients from January, 2007 to December, 2008 and compared them to bacterial drug resistance data in CHINET during the same period. The main specimens were from sputum culture, lavage fluid culture, lung biopsy tissue culture, and pleural effusion culture and bacterial or fungal cultures were performed on these specimens accordingly. Drug susceptibility was tested for positive bacterial cultures using disk diffusion (Kirby-Bauer method) and E Test strips in which results were determined based on the criteria of CLSI (2007). A total of 371 pathogen strains from ILD patients, including 306 bacterial strains and 65 fungal strains were isolated and cultured. Five main bacterial strains and their distribution were as follows: Klebsiella pneumoniae (31.7%), Pseudomonas aeruginosa (20.6%), Acinetobacter (12.7%), Enterobacter cloacae (8.2%), and Staphylococcus aureus (7.8%). The results showed that ILD patients who had anti-infection treatment tended to have Gram-negative bacteria, whether they acquired an infection in the hospital or elsewhere. Drug resistance screening indicated that aminoglycosides and carbapenems had lower antibiotic resistance rates. In addition, we found that the usage of immunosuppressants was associated with the increased infection rate and number of pathogens that were isolated. In conclusion, aminoglycosides and carbapenems may be selected as a priority for secondary infection to control ILD progression. Meanwhile, the use of anti-MRSA/MRCNS drugs may be considered for Staphylococcus infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterization of the microbial community in a lotic environment to assess the effect of pollution on nitrifying and potentially pathogenic bacteria.

PubMed

Medeiros, J D; Araújo, L X; da Silva, V L; Diniz, C G; Cesar, D E; Del'Duca, A; Coelho, C M

2014-08-01

This study aimed to investigate microbes involved in the nitrogen cycle and potentially pathogenic bacteria from urban and rural sites of the São Pedro stream. Water samples were collected from two sites. A seasonal survey of bacterial abundance was conducted. The dissolved nutrient content was analysed. PCR and FISH analysis were performed to identify and quantify microbes involved in the nitrogen cycle and potentially pathogenic bacteria. The seasonal survey revealed that the bacterial abundance was similar along the year on the rural area but varied on the urban site. Higher concentration of dissolved nutrients in the urban area indicated a eutrophic system. Considering the nitrifying microbes, the genus Nitrobacter was found, especially in the urban area, and may act as the principal bacteria in converting nitrite into nitrate at this site. The molecular markers napA, amoA, and nfrA were more accumulated at the urban site, justifying the higher content of nutrients metabolised by these enzymes. Finally, high intensity of amplicons from Enterococcus, Streptococcus, Bacteroides/Prevotella/Porphyromonas, Salmonella, S. aureus, P. aeruginosa and the diarrheagenic lineages of E. coli were observed at the urban site. These results indicate a change in the structure of the microbial community imposed by anthrophic actions. The incidence of pathogenic bacteria in aquatic environments is of particular importance to public health, emphasising the need for sewage treatment to minimise the environmental impacts associated with urbanisation.

Pseudogymnoascus destructans transcriptome changes during white-nose syndrome infections

PubMed Central

Reeder, Sophia M.; Palmer, Jonathan M.; Prokkola, Jenni M.; Lilley, Thomas M.; Reeder, DeeAnn M.

2017-01-01

ABSTRACT White nose syndrome (WNS) is caused by the psychrophilic fungus Pseudogymnoascus destructans that can grow in the environment saprotrophically or parasitically by infecting hibernating bats. Infections are pathological in many species of North American bats, disrupting hibernation and causing mortality. To determine what fungal pathways are involved in infection of living tissue, we examined fungal gene expression using RNA-Seq. We compared P. destructans gene expression when grown in culture to that during infection of a North American bat species, Myotis lucifugus, that shows high WNS mortality. Cultured P. destructans was grown at 10 to 14 C and P. destructans growing in vivo was presumably exposed to temperatures ranging from 4 to 8 C during torpor and up to 37 C during periodic arousals. We found that when P. destructans is causing WNS, the most significant differentially expressed genes were involved in heat shock responses, cell wall remodeling, and micronutrient acquisition. These results indicate that this fungal pathogen responds to host-pathogen interactions by regulating gene expression in ways that may contribute to evasion of host responses. Alterations in fungal cell wall structures could allow P. destructans to avoid detection by host pattern recognition receptors and antibody responses. This study has also identified several fungal pathways upregulated during WNS infection that may be candidates for mitigating infection pathology. By identifying host-specific pathogen responses, these observations have important implications for host-pathogen evolutionary relationships in WNS and other fungal diseases. PMID:28614673

Pseudogymnoascus destructans transcriptome changes during white-nose syndrome infections.

PubMed

Reeder, Sophia M; Palmer, Jonathan M; Prokkola, Jenni M; Lilley, Thomas M; Reeder, DeeAnn M; Field, Kenneth A

2017-11-17

White nose syndrome (WNS) is caused by the psychrophilic fungus Pseudogymnoascus destructans that can grow in the environment saprotrophically or parasitically by infecting hibernating bats. Infections are pathological in many species of North American bats, disrupting hibernation and causing mortality. To determine what fungal pathways are involved in infection of living tissue, we examined fungal gene expression using RNA-Seq. We compared P. destructans gene expression when grown in culture to that during infection of a North American bat species, Myotis lucifugus, that shows high WNS mortality. Cultured P. destructans was grown at 10 to 14 C and P. destructans growing in vivo was presumably exposed to temperatures ranging from 4 to 8 C during torpor and up to 37 C during periodic arousals. We found that when P. destructans is causing WNS, the most significant differentially expressed genes were involved in heat shock responses, cell wall remodeling, and micronutrient acquisition. These results indicate that this fungal pathogen responds to host-pathogen interactions by regulating gene expression in ways that may contribute to evasion of host responses. Alterations in fungal cell wall structures could allow P. destructans to avoid detection by host pattern recognition receptors and antibody responses. This study has also identified several fungal pathways upregulated during WNS infection that may be candidates for mitigating infection pathology. By identifying host-specific pathogen responses, these observations have important implications for host-pathogen evolutionary relationships in WNS and other fungal diseases.

Changes in leptospirosis etiology in animals and humans.

PubMed

Vasylieva, Natalia; Andreychyn, Mykhaylo; Kravchuk, Yulia; Chervinska, Оlena; Iosyk, Iaryna

2017-12-23

Leptospirosis is endemic in Ternopil region. In Ukraine, the disease is registered in almost all regions, including the Ternopil region. The aim of the research is to study the regularities of epidemic and epizootic processes of leptospirosis, and the circulation of its pathogens among different sources (small mammals, animals) and humans. Etiologic spectrum of leptospirosis registered in Ternopil region in 1972-2016 among small mammals, farm animals and sick people was studied. Due to the analysis of pathogens circulation among different sources (small mammals, animals), as well as the annual morbidity in humans, it was proved that new leptospira serovars are endemic and brought into the regions mostly by farm animals. Farm animals introduce the infection to humans through the environment, sometimes within 3-5-years. The spread was observed of pathogen serovars, which are new in certain areas, among all types of mouse-like small mammals and rats. It was established that livestock and small mammals are parallel reservoirs. In the regions with endemic species, the structural modification in the etiology of leptospirosis in humans is caused by additional reservoirs among animals, as well as the circulation of other pathogen serovars that were absent in the main natural reservoir, i.e. mouse-like small mammals and rats. The constant monitoring of the population, contamination and carrier state of mouse-like small mammals, rats and farm animals, is required In order to predict the future epidemiological situation on leptospirosis among the population and to improve leptospirosis diagnosis.

Uncertainty in Model Predictions of Vibrio Vulnificus Response to Climate Variability and Change: A Chesapeake Bay Case Study

NASA Technical Reports Server (NTRS)

Urquhart, Erin A.; Zaitchik, Benjamin F.; Waugh, Darryn W.; Guikema, Seth D.; Del Castillo, Carlos E.

2014-01-01

The effect that climate change and variability will have on waterborne bacteria is a topic of increasing concern for coastal ecosystems, including the Chesapeake Bay. Surface water temperature trends in the Bay indicate a warming pattern of roughly 0.3-0.4 C per decade over the past 30 years. It is unclear what impact future warming will have on pathogens currently found in the Bay, including Vibrio spp. Using historical environmental data, combined with three different statistical models of Vibrio vulnificus probability, we explore the relationship between environmental change and predicted Vibrio vulnificus presence in the upper Chesapeake Bay. We find that the predicted response of V. vulnificus probability to high temperatures in the Bay differs systematically between models of differing structure. As existing publicly available datasets are inadequate to determine which model structure is most appropriate, the impact of climatic change on the probability of V. vulnificus presence in the Chesapeake Bay remains uncertain. This result points to the challenge of characterizing climate sensitivity of ecological systems in which data are sparse and only statistical models of ecological sensitivity exist.

Origin, Migration Routes and Worldwide Population Genetic Structure of the Wheat Yellow Rust Pathogen Puccinia striiformis f.sp. tritici

PubMed Central

Ali, Sajid; Gladieux, Pierre; Leconte, Marc; Gautier, Angélique; Justesen, Annemarie F.; Hovmøller, Mogens S.; Enjalbert, Jérôme; de Vallavieille-Pope, Claude

2014-01-01

Analyses of large-scale population structure of pathogens enable the identification of migration patterns, diversity reservoirs or longevity of populations, the understanding of current evolutionary trajectories and the anticipation of future ones. This is particularly important for long-distance migrating fungal pathogens such as Puccinia striiformis f.sp. tritici (PST), capable of rapid spread to new regions and crop varieties. Although a range of recent PST invasions at continental scales are well documented, the worldwide population structure and the center of origin of the pathogen were still unknown. In this study, we used multilocus microsatellite genotyping to infer worldwide population structure of PST and the origin of new invasions based on 409 isolates representative of distribution of the fungus on six continents. Bayesian and multivariate clustering methods partitioned the set of multilocus genotypes into six distinct genetic groups associated with their geographical origin. Analyses of linkage disequilibrium and genotypic diversity indicated a strong regional heterogeneity in levels of recombination, with clear signatures of recombination in the Himalayan (Nepal and Pakistan) and near-Himalayan regions (China) and a predominant clonal population structure in other regions. The higher genotypic diversity, recombinant population structure and high sexual reproduction ability in the Himalayan and neighboring regions suggests this area as the putative center of origin of PST. We used clustering methods and approximate Bayesian computation (ABC) to compare different competing scenarios describing ancestral relationship among ancestral populations and more recently founded populations. Our analyses confirmed the Middle East-East Africa as the most likely source of newly spreading, high-temperature-adapted strains; Europe as the source of South American, North American and Australian populations; and Mediterranean-Central Asian populations as the origin of South African populations. Although most geographic populations are not markedly affected by recent dispersal events, this study emphasizes the influence of human activities on recent long-distance spread of the pathogen. PMID:24465211

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.

Gene flow and pathogen transmission among bobcats (Lynx rufus) in a fragmented urban landscape

USGS Publications Warehouse

Lee, Justin S.; Ruell, Emily W.; Boydston, Erin E.; Lyren, Lisa M.; Alonso, Robert S.; Troyer, Jennifer L.; Crooks, Kevin R.; VandeWoude, Sue

2012-01-01

Urbanization can result in the fragmentation of once contiguous natural landscapes into a patchy habitat interspersed within a growing urban matrix. Animals living in fragmented landscapes often have reduced movement among habitat patches because of avoidance of intervening human development, which potentially leads to both reduced gene flow and pathogen transmission between patches. Mammalian carnivores with large home ranges, such as bobcats (Lynx rufus), may be particularly sensitive to habitat fragmentation. We performed genetic analyses on bobcats and their directly transmitted viral pathogen, feline immunodeficiency virus (FIV), to investigate the effects of urbanization on bobcat movement. We predicted that urban development, including major freeways, would limit bobcat movement and result in genetically structured host and pathogen populations. We analysed molecular markers from 106 bobcats and 19 FIV isolates from seropositive animals in urban southern California. Our findings indicate that reduced gene flow between two primary habitat patches has resulted in genetically distinct bobcat subpopulations separated by urban development including a major highway. However, the distribution of genetic diversity among FIV isolates determined through phylogenetic analyses indicates that pathogen genotypes are less spatially structured--exhibiting a more even distribution between habitat fragments. We conclude that the types of movement and contact sufficient for disease transmission occur with enough frequency to preclude structuring among the viral population, but that the bobcat population is structured owing to low levels of effective bobcat migration resulting in gene flow. We illustrate the utility in using multiple molecular markers that differentially detect movement and gene flow between subpopulations when assessing connectivity.

High levels of diversity and population structure in the potato late blight pathogen at the Mexico centre of origin.

PubMed

Wang, Jianan; Fernández-Pavía, Sylvia P; Larsen, Meredith M; Garay-Serrano, Edith; Gregorio-Cipriano, Rosario; Rodríguez-Alvarado, Gerardo; Grünwald, Niklaus J; Goss, Erica M

2017-02-01

Globally destructive crop pathogens often emerge by migrating out of their native ranges. These pathogens are often diverse at their centre of origin and may exhibit adaptive variation in the invaded range via multiple introductions from different source populations. However, source populations are generally unidentified or poorly studied compared to invasive populations. Phytophthora infestans, the causal agent of late blight, is one of the most costly pathogens of potato and tomato worldwide. Mexico is the centre of origin and diversity of P. infestans and migration events out of Mexico have enormously impacted disease dynamics in North America and Europe. The debate over the origin of the pathogen, and population studies of P. infestans in Mexico, has focused on the Toluca Valley, whereas neighbouring regions have been little studied. We examined the population structure of P. infestans across central Mexico, including samples from Michoacán, Tlaxcala and Toluca. We found high levels of diversity consistent with sexual reproduction in Michoacán and Tlaxcala and population subdivision that was strongly associated with geographic region. We determined that population structure in central Mexico has contributed to diversity in introduced populations based on relatedness of U.S. clonal lineages to Mexican isolates from different regions. Our results suggest that P. infestans exists as a metapopulation in central Mexico, and this population structure could be contributing to the repeated re-emergence of P. infestans in the United States and elsewhere. © 2016 John Wiley & Sons Ltd.

Temperature-responsive in vitro RNA structurome of Yersinia pseudotuberculosis.

PubMed

Righetti, Francesco; Nuss, Aaron M; Twittenhoff, Christian; Beele, Sascha; Urban, Kristina; Will, Sebastian; Bernhart, Stephan H; Stadler, Peter F; Dersch, Petra; Narberhaus, Franz

2016-06-28

RNA structures are fundamentally important for RNA function. Dynamic, condition-dependent structural changes are able to modulate gene expression as shown for riboswitches and RNA thermometers. By parallel analysis of RNA structures, we mapped the RNA structurome of Yersinia pseudotuberculosis at three different temperatures. This human pathogen is exquisitely responsive to host body temperature (37 °C), which induces a major metabolic transition. Our analysis profiles the structure of more than 1,750 RNAs at 25 °C, 37 °C, and 42 °C. Average mRNAs tend to be unstructured around the ribosome binding site. We searched for 5'-UTRs that are folded at low temperature and identified novel thermoresponsive RNA structures from diverse gene categories. The regulatory potential of 16 candidates was validated. In summary, we present a dynamic bacterial RNA structurome and find that the expression of virulence-relevant functions in Y. pseudotuberculosis and reprogramming of its metabolism in response to temperature is associated with a restructuring of numerous mRNAs.

Molecular basis of ubiquitin recognition by the autophagy receptor CALCOCO2

PubMed Central

Xie, Xingqiao; Li, Faxiang; Wang, Yuanyuan; Wang, Yingli; Lin, Zhijie; Cheng, Xiaofang; Liu, Jianping; Chen, Changbin; Pan, Lifeng

2015-01-01

The autophagy receptor CALCOCO2/NDP52 functions as a bridging adaptor and plays an essential role in the selective autophagic degradation of invading pathogens by specifically recognizing ubiquitin-coated intracellular pathogens and subsequently targeting them to the autophagic machinery; thereby it is required for innate immune defense against a range of infectious pathogens in mammals. However, the mechanistic basis underlying CALCOCO2-mediated specific recognition of ubiqutinated pathogens is still unknown. Here, using biochemical and structural analyses, we demonstrated that the cargo-binding region of CALCOCO2 contains a dynamic unconventional zinc finger as well as a C2H2-type zinc-finger, and only the C2H2-type zinc finger specifically recognizes mono-ubiquitin or poly-ubiquitin chains. In addition to elucidating the specific ubiquitin recognition mechanism of CALCOCO2, the structure of the CALCOCO2 C2H2-type zinc finger in complex with mono-ubiquitin also uncovers a unique zinc finger-binding mode for ubiquitin. Our findings provide mechanistic insight into how CALCOCO2 targets ubiquitin-decorated pathogens for autophagic degradations. PMID:26506893

Invasive forest pathogens: Summary of issues, critical needs, and future goals for Forest Service Research and Development

Treesearch

Ned B. Klopfenstein; Jennifer Juzwik; Michael E. Ostry; Mee-Sook Kim; Paul J. Zambino; Robert C. Venette; Bryce A. Richardson; John E. Lundquist; D. Jean Lodge; Jessie A. Glaeser; Susan J. Frankel; William J. Otrosina; Pauline Spaine; Brian W. Geils

2010-01-01

Invasive pathogens have caused immeasurable ecological and economic damage to forest ecosystems. Damage will undoubtedly increase over time due to increased introductions and evolution of invasive pathogens in concert with complex environmental disturbances, such as climate change. Forest Service Research and Development must fulfill critical roles and responsibilities...

Historical and current roles of insects and pathogens in eastern Oregon and Washington forested landscapes.

Treesearch

P.F. Hessburg; R.G. Mitchell; G.M. Filip

1994-01-01

This paper examines by climax conifer series, historical and current roles of many important pathogens and insects of interior Northwest coniferous forests, and their unique responses to changing successional conditions resulting from management. Insects and pathogens of the subalpine fir and mountain hemlock series historically reduced inter-tree competition for site...

Evolution and genome architecture in fungal plant pathogens.

PubMed

Möller, Mareike; Stukenbrock, Eva H

2017-12-01

The fungal kingdom comprises some of the most devastating plant pathogens. Sequencing the genomes of fungal pathogens has shown a remarkable variability in genome size and architecture. Population genomic data enable us to understand the mechanisms and the history of changes in genome size and adaptive evolution in plant pathogens. Although transposable elements predominantly have negative effects on their host, fungal pathogens provide prominent examples of advantageous associations between rapidly evolving transposable elements and virulence genes that cause variation in virulence phenotypes. By providing homogeneous environments at large regional scales, managed ecosystems, such as modern agriculture, can be conducive for the rapid evolution and dispersal of pathogens. In this Review, we summarize key examples from fungal plant pathogen genomics and discuss evolutionary processes in pathogenic fungi in the context of molecular evolution, population genomics and agriculture.

Dynamics of Legionella spp. and bacterial populations during the proliferation of L. pneumophila in a cooling tower facility.

PubMed

Wéry, Nathalie; Bru-Adan, Valérie; Minervini, Céline; Delgénes, Jean-Philippe; Garrelly, Laurent; Godon, Jean-Jacques

2008-05-01

The dynamics of Legionella spp. and of dominant bacteria were investigated in water from a cooling tower plant over a 9-month period which included several weeks when Legionella pneumophila proliferated. The structural diversity of both the bacteria and the Legionella spp. was monitored by a fingerprint technique, single-strand conformation polymorphism, and Legionella spp. and L. pneumophila were quantified by real-time quantitative PCR. The structure of the bacterial community did not change over time, but it was perturbed periodically by chemical treatment or biofilm detachment. In contrast, the structure of the Legionella sp. population changed in different periods, its dynamics at times showing stability but also a rapid major shift during the proliferation of L. pneumophila in July. The dynamics of the Legionella spp. and of dominant bacteria were not correlated. In particular, no change in the bacterial community structure was observed during the proliferation of L. pneumophila. Legionella spp. present in the cooling tower system were identified by cloning and sequencing of 16S rRNA genes. A high diversity of Legionella spp. was observed before proliferation, including L. lytica, L. fallonii, and other Legionella-like amoebal pathogen types, along with as-yet-undescribed species. During the proliferation of L. pneumophila, Legionella sp. diversity decreased significantly, L. fallonii and L. pneumophila being the main species recovered.

Dynamics of Legionella spp. and Bacterial Populations during the Proliferation of L. pneumophila in a Cooling Tower Facility▿

PubMed Central

Wéry, Nathalie; Bru-Adan, Valérie; Minervini, Céline; Delgénes, Jean-Philippe; Garrelly, Laurent; Godon, Jean-Jacques

2008-01-01

The dynamics of Legionella spp. and of dominant bacteria were investigated in water from a cooling tower plant over a 9-month period which included several weeks when Legionella pneumophila proliferated. The structural diversity of both the bacteria and the Legionella spp. was monitored by a fingerprint technique, single-strand conformation polymorphism, and Legionella spp. and L. pneumophila were quantified by real-time quantitative PCR. The structure of the bacterial community did not change over time, but it was perturbed periodically by chemical treatment or biofilm detachment. In contrast, the structure of the Legionella sp. population changed in different periods, its dynamics at times showing stability but also a rapid major shift during the proliferation of L. pneumophila in July. The dynamics of the Legionella spp. and of dominant bacteria were not correlated. In particular, no change in the bacterial community structure was observed during the proliferation of L. pneumophila. Legionella spp. present in the cooling tower system were identified by cloning and sequencing of 16S rRNA genes. A high diversity of Legionella spp. was observed before proliferation, including L. lytica, L. fallonii, and other Legionella-like amoebal pathogen types, along with as-yet-undescribed species. During the proliferation of L. pneumophila, Legionella sp. diversity decreased significantly, L. fallonii and L. pneumophila being the main species recovered. PMID:18390683

New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease.

PubMed

Rühli, Frank Jakobus; Henneberg, Maciej

2013-04-29

Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations.

Frontiers for research on the ecology of plant-pathogenic bacteria: fundamentals for sustainability: Challenges in Bacterial Molecular Plant Pathology.

PubMed

Morris, Cindy E; Barny, Marie-Anne; Berge, Odile; Kinkel, Linda L; Lacroix, Christelle

2017-02-01

Methods to ensure the health of crops owe their efficacy to the extent to which we understand the ecology and biology of environmental microorganisms and the conditions under which their interactions with plants lead to losses in crop quality or yield. However, in the pursuit of this knowledge, notions of the ecology of plant-pathogenic microorganisms have been reduced to a plant-centric and agro-centric focus. With increasing global change, i.e. changes that encompass not only climate, but also biodiversity, the geographical distribution of biomes, human demographic and socio-economic adaptations and land use, new plant health problems will emerge via a range of processes influenced by these changes. Hence, knowledge of the ecology of plant pathogens will play an increasingly important role in the anticipation and response to disease emergence. Here, we present our opinion on the major challenges facing the study of the ecology of plant-pathogenic bacteria. We argue that the discovery of markedly novel insights into the ecology of plant-pathogenic bacteria is most likely to happen within a framework of more extensive scales of space, time and biotic interactions than those that currently guide much of the research on these bacteria. This will set a context that is more propitious for the discovery of unsuspected drivers of the survival and diversification of plant-pathogenic bacteria and of the factors most critical for disease emergence, and will set the foundation for new approaches to the sustainable management of plant health. We describe the contextual background of, justification for and specific research questions with regard to the following challenges: Development of terminology to describe plant-bacterial relationships in terms of bacterial fitness. Definition of the full scope of the environments in which plant-pathogenic bacteria reside or survive. Delineation of pertinent phylogenetic contours of plant-pathogenic bacteria and naming of strains independent of their presumed life style. Assessment of how traits of plant-pathogenic bacteria evolve within the overall framework of their life history. Exploration of possible beneficial ecosystem services contributed to by plant-pathogenic bacteria. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Linking environmental nutrient enrichment and disease emergence in humans and wildlife

PubMed Central

Johnson, Pieter T. J.; Townsend, Alan R.; Cleveland, Cory C.; Glibert, Patricia M.; Howarth, Robert W.; McKenzie, Valerie J.; Rejmankova, Eliska; Ward, Mary H.

2009-01-01

Worldwide increases in the numbers of human and wildlife diseases present ecologists with the challenge of understanding how large-scale environmental changes affect host-parasite interactions. One of the most profound changes to Earth’s ecosystems is the alteration of global nutrient cycles, including those of phosphorus (P) and especially nitrogen (N). Alongside the obvious direct benefits of nutrient application for food production, growing evidence suggests that anthropogenic inputs of N and P can indirectly affect the abundance of infectious and noninfectious pathogens, sometimes leading to epidemic conditions. However, the mechanisms underpinning observed correlations, and how such patterns vary with disease type, have long remained conjectural. Here, we discuss recent experimental advances in this area to critically evaluate the relationship between environmental nutrient enrichment and disease. Given the inter-related nature of human and wildlife disease emergence, we include a broad range of human and wildlife examples from terrestrial, marine and freshwater ecosystems. We examine the consequences of nutrient pollution on directly transmitted, vector-borne, complex life cycle, and noninfectious pathogens, including West Nile virus, malaria, harmful algal blooms, coral reef diseases and amphibian malformations. Our synthetic examination suggests that the effects of environmental nutrient enrichment on disease are complex and multifaceted, varying with the type of pathogen, host species and condition, attributes of the ecosystem and the degree of enrichment; some pathogens increase in abundance whereas others decline or disappear. Nevertheless, available evidence indicates that ecological changes associated with nutrient enrichment often exacerbate infection and disease caused by generalist parasites with direct or simple life cycles. Observed mechanisms include changes in host/vector density, host distribution, infection resistance, pathogen virulence or toxicity, or the direct supplementation of pathogens. Collectively, these pathogens may be particularly dangerous because they can continue to cause mortality even as their hosts decline, potentially leading to sustained epidemics or chronic pathology. We suggest that interactions between nutrient enrichment and disease will become increasingly important in tropical and subtropical regions, where forecasted increases in nutrient application will occur in an environment rich with infectious pathogens. We emphasize the importance of careful disease management in conjunction with continued intensification of global nutrient cycles. PMID:20349828

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.

Identification of a novel type III secretion-associated outer membrane-bound protein from Xanthomonas campestris pv. campestris

PubMed Central

Li, Lei; Li, Rui-Fang; Ming, Zhen-Hua; Lu, Guang-Tao; Tang, Ji-Liang

2017-01-01

Many bacterial pathogens employ the type III secretion system (T3SS) to translocate effector proteins into eukaryotic cells to overcome host defenses. To date, most of our knowledge about the T3SS molecular architecture comes from the studies on animal pathogens. In plant pathogens, nine Hrc proteins are believed to be structural components of the T3SS, of which HrcC and HrcJ form the outer and inner rings of the T3SS, respectively. Here, we demonstrated that a novel outer membrane-bound protein (HpaM) of Xanthomonas campestris pv. campestris is critical for the type III secretion and is structurally and functionally conserved in phytopathogenic Xanthomonas spp. We showed that the C-terminus of HpaM extends into the periplasm to interact physically with HrcJ and the middle part of HpaM interacts physically with HrcC. It is clear that the outer and inner rings compose the main basal body of the T3SS apparatus in animal pathogens. Therefore, we presume that HpaM may act as a T3SS structural component, or play a role in assisting assembling or affecting the stability of the T3SS apparatus. HpaM is a highly prevalent and specific protein in Xanthomonas spp., suggesting that the T3SS of Xanthomonas is distinctive in some aspects from other pathogens. PMID:28198457

Systemic acquired resistance in moss: further evidence for conserved defense mechanisms in plants.

PubMed

Winter, Peter S; Bowman, Collin E; Villani, Philip J; Dolan, Thomas E; Hauck, Nathanael R

2014-01-01

Vascular plants possess multiple mechanisms for defending themselves against pathogens. One well-characterized defense mechanism is systemic acquired resistance (SAR). In SAR, a plant detects the presence of a pathogen and transmits a signal throughout the plant, inducing changes in the expression of various pathogenesis-related (PR) genes. Once SAR is established, the plant is capable of mounting rapid responses to subsequent pathogen attacks. SAR has been characterized in numerous angiosperm and gymnosperm species; however, despite several pieces of evidence suggesting SAR may also exist in non-vascular plants6-8, its presence in non-vascular plants has not been conclusively demonstrated, in part due to the lack of an appropriate culture system. Here, we describe and use a novel culture system to demonstrate that the moss species Amblystegium serpens does initiate a SAR-like reaction upon inoculation with Pythium irregulare, a common soil-borne oomycete. Infection of A. serpens gametophores by P. irregulare is characterized by localized cytoplasmic shrinkage within 34 h and chlorosis and necrosis within 7 d of inoculation. Within 24 h of a primary inoculation (induction), moss gametophores grown in culture became highly resistant to infection following subsequent inoculation (challenge) by the same pathogen. This increased resistance was a response to the pathogen itself and not to physical wounding. Treatment with β-1,3 glucan, a structural component of oomycete cell walls, was equally effective at triggering SAR. Our results demonstrate, for the first time, that this important defense mechanism exists in a non-vascular plant, and, together with previous studies, suggest that SAR arose prior to the divergence of vascular and non-vascular plants. In addition, this novel moss - pathogen culture system will be valuable for future characterization of the mechanism of SAR in moss, which is necessary for a better understanding of the evolutionary history of SAR in plants.

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PubMed Central

Sato, Hiromi

2017-01-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection. PMID:28750011

Leptospira interrogans causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells.

PubMed

Sato, Hiromi; Coburn, Jenifer

2017-07-01

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.

The heritage of pathogen pressures and ancient demography in the human innate-immunity CD209/CD209L region.

PubMed

Barreiro, Luis B; Patin, Etienne; Neyrolles, Olivier; Cann, Howard M; Gicquel, Brigitte; Quintana-Murci, Lluís

2005-11-01

The innate immunity system constitutes the first line of host defense against pathogens. Two closely related innate immunity genes, CD209 and CD209L, are particularly interesting because they directly recognize a plethora of pathogens, including bacteria, viruses, and parasites. Both genes, which result from an ancient duplication, possess a neck region, made up of seven repeats of 23 amino acids each, known to play a major role in the pathogen-binding properties of these proteins. To explore the extent to which pathogens have exerted selective pressures on these innate immunity genes, we resequenced them in a group of samples from sub-Saharan Africa, Europe, and East Asia. Moreover, variation in the number of repeats of the neck region was defined in the entire Human Genome Diversity Panel for both genes. Our results, which are based on diversity levels, neutrality tests, population genetic distances, and neck-region length variation, provide genetic evidence that CD209 has been under a strong selective constraint that prevents accumulation of any amino acid changes, whereas CD209L variability has most likely been shaped by the action of balancing selection in non-African populations. In addition, our data point to the neck region as the functional target of such selective pressures: CD209 presents a constant size in the neck region populationwide, whereas CD209L presents an excess of length variation, particularly in non-African populations. An additional interesting observation came from the coalescent-based CD209 gene tree, whose binary topology and time depth (approximately 2.8 million years ago) are compatible with an ancestral population structure in Africa. Altogether, our study has revealed that even a short segment of the human genome can uncover an extraordinarily complex evolutionary history, including different pathogen pressures on host genes as well as traces of admixture among archaic hominid populations.

Herbivores and pathogens on Alnus viridis subsp. fruticosa in interior Alaska: effects of leaf, tree, and neighbour characteristics on damage levels

Treesearch

Christa P.H. Mulder; Bitty A. Roy; Sabine Gusewell

2008-01-01

Parasite damage strongly affects dynamics of boreal forests. Damage levels may be affected by climate change, either directly or indirectly through changes in properties of host trees. We examined how herbivore and pathogen damage in Alnus viridis subsp. fruticosa (Rupr.) Nym. depend on leaf morphology and chemistry, tree size...

Disease Risk in a Dynamic Environment: The Spread of Tick-Borne Pathogens in Minnesota, USA

PubMed Central

Robinson, Stacie J.; Neitzel, David F.; Moen, Ronald A.; Craft, Meggan E.; Hamilton, Karin E.; Johnson, Lucinda B.; Mulla, David J.; Munderloh, Ulrike G.; Redig, Patrick T.; Smith, Kirk E.; Turner, Clarence L.; Umber, Jamie K.; Pelican, Katharine M.

2015-01-01

As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease. PMID:25281302

Non-Cholera Vibrios: The Microbial Barometer of Climate Change.

PubMed

Baker-Austin, Craig; Trinanes, Joaquin; Gonzalez-Escalona, Narjol; Martinez-Urtaza, Jaime

2017-01-01

There is a growing interest in the role of climate change in driving the spread of waterborne infectious diseases, such as those caused by bacterial pathogens. One particular group of pathogenic bacteria - vibrios - are a globally important cause of diseases in humans and aquatic animals. These Gram-negative bacteria, including the species Vibrio vulnificus, Vibrio parahaemolyticus and Vibrio cholerae, grow in warm, low-salinity waters, and their abundance in the natural environment mirrors ambient environmental temperatures. In a rapidly warming marine environment, there are greater numbers of human infections, and most notably outbreaks linked to extreme weather events such as heatwaves in temperate regions such as Northern Europe. Because the growth of pathogenic vibrios in the natural environment is largely dictated by temperature, we argue that this group of pathogens represents an important and tangible barometer of climate change in marine systems. We provide a number of specific examples of the impacts of climate change on this group of bacteria and their associated diseases, and discuss advanced strategies to improve our understanding of these emerging waterborne diseases through the integration of microbiological, genomic, epidemiological, climatic, and ocean sciences. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Disease risk in a dynamic environment: the spread of tick-borne pathogens in Minnesota, USA.

PubMed

Robinson, Stacie J; Neitzel, David F; Moen, Ronald A; Craft, Meggan E; Hamilton, Karin E; Johnson, Lucinda B; Mulla, David J; Munderloh, Ulrike G; Redig, Patrick T; Smith, Kirk E; Turner, Clarence L; Umber, Jamie K; Pelican, Katharine M

2015-03-01

As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease.

Identification of six novel mutations in Iranian patients with maple syrup urine disease and their in silico analysis.

PubMed

Abiri, Maryam; Karamzadeh, Razieh; Karimipoor, Morteza; Ghadami, Shirin; Alaei, Mohammad Reza; Bagheri, Samira Dabagh; Bagherian, Hamideh; Setoodeh, Aria; Noori-Daloii, Mohammad Reza; Sirous Zeinali

2016-04-01

Maple syrup urine disease (MSUD) is a rare inborn error of branched-chain amino acid metabolism. The disease prevalence is higher in populations with elevated rate of consanguineous marriages such as Iran. Different types of disease causing mutations have been previously reported in BCKDHA, BCKDHB, DBT and DLD genes known to be responsible for MSUD phenotype. In this study, two sets of multiplex polymorphic STR (Short Tandem Repeat) markers linked to the above genes were used to aid in homozygosity mapping in order to find probable pathogenic change(s) in the studied families. The families who showed homozygote haplotype for the BCKDHA gene were subsequently sequenced. Our findings showed that exons 2, 4 and 6 contain most of the mutations which are novel. The changes include two single nucleotide deletion (i.e. c. 143delT and c.702delT), one gross deletion covering the whole exon four c.(375+1_376-1)_(8849+1_885-1), two splice site changes (c.1167+1G>T, c. 288+1G>A), and one point mutation (c.731G>A). Computational approaches were used to analyze these two novel mutations in terms of their impact on protein structure. Computational structural modeling indicated that these mutations might affect structural stability and multimeric assembly of branched-chain α-keto acid dehydrogenase complex (BCKDC). Copyright © 2016. Published by Elsevier B.V.

Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.

PubMed

Briggs, C E; Rucinski, D; Rosenfeld, P J; Hirose, T; Berson, E L; Dryja, T P

2001-09-01

To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD). One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified. The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes. This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.

Alteration of host-pathogen interactions in the wake of climate change - Increasing risk for shellfish associated infections?

PubMed

Hernroth, Bodil E; Baden, Susanne P

2018-02-01

The potential for climate-related spread of infectious diseases through marine systems has been highlighted in several reports. With this review we want to draw attention to less recognized mechanisms behind vector-borne transmission pathways to humans. We have focused on how the immune systems of edible marine shellfish, the blue mussels and Norway lobsters, are affected by climate related environmental stressors. Future ocean acidification (OA) and warming due to climate change constitute a gradually increasing persistent stress with negative trade-off for many organisms. In addition, the stress of recurrent hypoxia, inducing high levels of bioavailable manganese (Mn) is likely to increase in line with climate change. We summarized that OA, hypoxia and elevated levels of Mn did have an overall negative effect on immunity, in some cases also with synergistic effects. On the other hand, moderate increase in temperature seems to have a stimulating effect on antimicrobial activity and may in a future warming scenario counteract the negative effects. However, rising sea surface temperature and climate events causing high land run-off promote the abundance of naturally occurring pathogenic Vibrio and will in addition, bring enteric pathogens which are circulating in society into coastal waters. Moreover, the observed impairments of the immune defense enhance the persistence and occurrence of pathogens in shellfish. This may increase the risk for direct transmission of pathogens to consumers. It is thus essential that in the wake of climate change, sanitary control of coastal waters and seafood must recognize and adapt to the expected alteration of host-pathogen interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization, Microbial Community Structure, and Pathogen Occurrence in Urban Faucet Biofilms in South China

PubMed Central

Lin, Huirong; Zhang, Shuting; Gong, Song; Zhang, Shenghua; Yu, Xin

2015-01-01

The composition and microbial community structure of the drinking water system biofilms were investigated using microstructure analysis and 454 pyrosequencing technique in Xiamen city, southeast of China. SEM (scanning electron microscope) results showed different features of biofilm morphology in different fields of PVC pipe. Extracellular matrix material and sparse populations of bacteria (mainly rod-shaped and coccoid) were observed. CLSM (confocal laser scanning microscope) revealed different distributions of attached cells, extracellular proteins, α-polysaccharides, and β-polysaccharides. The biofilms had complex bacterial compositions. Differences in bacteria diversity and composition from different tap materials and ages were observed. Proteobacteria was the common and predominant group in all biofilms samples. Some potential pathogens (Legionellales, Enterobacteriales, Chromatiales, and Pseudomonadales) and corrosive microorganisms were also found in the biofilms. This study provides the information of characterization and visualization of the drinking water biofilms matrix, as well as the microbial community structure and opportunistic pathogens occurrence. PMID:26273617

Surface Proteins of Gram-Positive Pathogens: Using Crystallography to Uncover Novel Features in Drug and Vaccine Candidates

NASA Astrophysics Data System (ADS)

Baker, Edward N.; Proft, Thomas; Kang, Haejoo

Proteins displayed on the cell surfaces of pathogenic organisms are the front-line troops of bacterial attack, playing critical roles in colonization, infection and virulence. Although such proteins can often be recognized from genome sequence data, through characteristic sequence motifs, their functions are often unknown. One such group of surface proteins is attached to the cell surface of Gram-positive pathogens through the action of sortase enzymes. Some of these proteins are now known to form pili: long filamentous structures that mediate attachment to human cells. Crystallographic analyses of these and other cell surface proteins have uncovered novel features in their structure, assembly and stability, including the presence of inter- and intramolecular isopeptide crosslinks. This improved understanding of structures on the bacterial cell surface offers opportunities for the development of some new drug targets and for novel approaches to vaccine design.

Lack of Host Specialization on Winter Annual Grasses in the Fungal Seed Bank Pathogen Pyrenophora semeniperda

PubMed Central

Beckstead, Julie; Meyer, Susan E.; Ishizuka, Toby S.; McEvoy, Kelsey M.; Coleman, Craig E.

2016-01-01

Generalist plant pathogens may have wide host ranges, but many exhibit varying degrees of host specialization, with multiple pathogen races that have narrower host ranges. These races are often genetically distinct, with each race causing highest disease incidence on its host of origin. We examined host specialization in the seed pathogen Pyrenophora semeniperda by reciprocally inoculating pathogen strains from Bromus tectorum and from four other winter annual grass weeds (Bromus diandrus, Bromus rubens, Bromus arvensis and Taeniatherum caput-medusae) onto dormant seeds of B. tectorum and each alternate host. We found that host species varied in resistance and pathogen strains varied in aggressiveness, but there was no evidence for host specialization. Most variation in aggressiveness was among strains within populations and was expressed similarly on both hosts, resulting in a positive correlation between strain-level disease incidence on B. tectorum and on the alternate host. In spite of this lack of host specialization, we detected weak but significant population genetic structure as a function of host species using two neutral marker systems that yielded similar results. This genetic structure is most likely due to founder effects, as the pathogen is known to be dispersed with host seeds. All host species were highly susceptible to their own pathogen races. Tolerance to infection (i.e., the ability to germinate even when infected and thereby avoid seed mortality) increased as a function of seed germination rate, which in turn increased as dormancy was lost. Pyrenophora semeniperda apparently does not require host specialization to fully exploit these winter annual grass species, which share many life history features that make them ideal hosts for this pathogen. PMID:26950931

Colonization history, host distribution, anthropogenic influence and landscape features shape populations of white pine blister rust, an invasive alien tree pathogen.

PubMed

Brar, Simren; Tsui, Clement K M; Dhillon, Braham; Bergeron, Marie-Josée; Joly, David L; Zambino, P J; El-Kassaby, Yousry A; Hamelin, Richard C

2015-01-01

White pine blister rust is caused by the fungal pathogen Cronartium ribicola J.C. Fisch (Basidiomycota, Pucciniales). This invasive alien pathogen was introduced into North America at the beginning of the 20th century on pine seedlings imported from Europe and has caused serious economic and ecological impacts. In this study, we applied a population and landscape genetics approach to understand the patterns of introduction and colonization as well as population structure and migration of C. ribicola. We characterized 1,292 samples of C. ribicola from 66 geographic locations in North America using single nucleotide polymorphisms (SNPs) and evaluated the effect of landscape features, host distribution, and colonization history on the structure of these pathogen populations. We identified eastern and western genetic populations in North America that are strongly differentiated. Genetic diversity is two to five times higher in eastern populations than in western ones, which can be explained by the repeated accidental introductions of the pathogen into northeastern North America compared with a single documented introduction into western North America. These distinct genetic populations are maintained by a barrier to gene flow that corresponds to a region where host connectivity is interrupted. Furthermore, additional cryptic spatial differentiation was identified in western populations. This differentiation corresponds to landscape features, such as mountain ranges, and also to host connectivity. We also detected genetic differentiation between the pathogen populations in natural stands and plantations, an indication that anthropogenic movement of this pathogen still takes place. These results highlight the importance of monitoring this invasive alien tree pathogen to prevent admixture of eastern and western populations where different pathogen races occur.

Climate Change and Food Security: Health Impacts in Developed Countries

PubMed Central

Hooper, Lee; Abdelhamid, Asmaa; Bentham, Graham; Boxall, Alistair B.A.; Draper, Alizon; Fairweather-Tait, Susan; Hulme, Mike; Hunter, Paul R.; Nichols, Gordon; Waldron, Keith W.

2012-01-01

Background: Anthropogenic climate change will affect global food production, with uncertain consequences for human health in developed countries. Objectives: We investigated the potential impact of climate change on food security (nutrition and food safety) and the implications for human health in developed countries. Methods: Expert input and structured literature searches were conducted and synthesized to produce overall assessments of the likely impacts of climate change on global food production and recommendations for future research and policy changes. Results: Increasing food prices may lower the nutritional quality of dietary intakes, exacerbate obesity, and amplify health inequalities. Altered conditions for food production may result in emerging pathogens, new crop and livestock species, and altered use of pesticides and veterinary medicines, and affect the main transfer mechanisms through which contaminants move from the environment into food. All these have implications for food safety and the nutritional content of food. Climate change mitigation may increase consumption of foods whose production reduces greenhouse gas emissions. Impacts may include reduced red meat consumption (with positive effects on saturated fat, but negative impacts on zinc and iron intake) and reduced winter fruit and vegetable consumption. Developed countries have complex structures in place that may be used to adapt to the food safety consequences of climate change, although their effectiveness will vary between countries, and the ability to respond to nutritional challenges is less certain. Conclusions: Climate change will have notable impacts upon nutrition and food safety in developed countries, but further research is necessary to accurately quantify these impacts. Uncertainty about future impacts, coupled with evidence that climate change may lead to more variable food quality, emphasizes the need to maintain and strengthen existing structures and policies to regulate food production, monitor food quality and safety, and respond to nutritional and safety issues that arise. PMID:23124134

Climate change and food security: health impacts in developed countries.

PubMed

Lake, Iain R; Hooper, Lee; Abdelhamid, Asmaa; Bentham, Graham; Boxall, Alistair B A; Draper, Alizon; Fairweather-Tait, Susan; Hulme, Mike; Hunter, Paul R; Nichols, Gordon; Waldron, Keith W

2012-11-01

Anthropogenic climate change will affect global food production, with uncertain consequences for human health in developed countries. We investigated the potential impact of climate change on food security (nutrition and food safety) and the implications for human health in developed countries. Expert input and structured literature searches were conducted and synthesized to produce overall assessments of the likely impacts of climate change on global food production and recommendations for future research and policy changes. Increasing food prices may lower the nutritional quality of dietary intakes, exacerbate obesity, and amplify health inequalities. Altered conditions for food production may result in emerging pathogens, new crop and livestock species, and altered use of pesticides and veterinary medicines, and affect the main transfer mechanisms through which contaminants move from the environment into food. All these have implications for food safety and the nutritional content of food. Climate change mitigation may increase consumption of foods whose production reduces greenhouse gas emissions. Impacts may include reduced red meat consumption (with positive effects on saturated fat, but negative impacts on zinc and iron intake) and reduced winter fruit and vegetable consumption. Developed countries have complex structures in place that may be used to adapt to the food safety consequences of climate change, although their effectiveness will vary between countries, and the ability to respond to nutritional challenges is less certain. Climate change will have notable impacts upon nutrition and food safety in developed countries, but further research is necessary to accurately quantify these impacts. Uncertainty about future impacts, coupled with evidence that climate change may lead to more variable food quality, emphasizes the need to maintain and strengthen existing structures and policies to regulate food production, monitor food quality and safety, and respond to nutritional and safety issues that arise.

An emerging cyberinfrastructure for biodefense pathogen and pathogen-host data.

PubMed

Zhang, C; Crasta, O; Cammer, S; Will, R; Kenyon, R; Sullivan, D; Yu, Q; Sun, W; Jha, R; Liu, D; Xue, T; Zhang, Y; Moore, M; McGarvey, P; Huang, H; Chen, Y; Zhang, J; Mazumder, R; Wu, C; Sobral, B

2008-01-01

The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host-pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.

The community ecology of pathogens: coinfection, coexistence and community composition.

PubMed

Seabloom, Eric W; Borer, Elizabeth T; Gross, Kevin; Kendig, Amy E; Lacroix, Christelle; Mitchell, Charles E; Mordecai, Erin A; Power, Alison G

2015-04-01

Disease and community ecology share conceptual and theoretical lineages, and there has been a resurgence of interest in strengthening links between these fields. Building on recent syntheses focused on the effects of host community composition on single pathogen systems, we examine pathogen (microparasite) communities using a stochastic metacommunity model as a starting point to bridge community and disease ecology perspectives. Such models incorporate the effects of core community processes, such as ecological drift, selection and dispersal, but have not been extended to incorporate host-pathogen interactions, such as immunosuppression or synergistic mortality, that are central to disease ecology. We use a two-pathogen susceptible-infected (SI) model to fill these gaps in the metacommunity approach; however, SI models can be intractable for examining species-diverse, spatially structured systems. By placing disease into a framework developed for community ecology, our synthesis highlights areas ripe for progress, including a theoretical framework that incorporates host dynamics, spatial structuring and evolutionary processes, as well as the data needed to test the predictions of such a model. Our synthesis points the way for this framework and demonstrates that a deeper understanding of pathogen community dynamics will emerge from approaches working at the interface of disease and community ecology. © 2015 John Wiley & Sons Ltd/CNRS.

Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

PubMed Central

2011-01-01

Background Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic Erwinia pyrifoliae exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of Yersinia pestis. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells. Results Pla and Epo expressed in Escherichia coli are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed. Conclusions We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens. PMID:21310089

Species Identity Supersedes the Dilution Effect Concerning Hantavirus Prevalence at Sites across Texas and México.

PubMed

Milholland, Matthew T; Castro-Arellano, Iván; Arellano, Elizabeth; Nava-García, Elizabeth; Rangel-Altamirano, Guadalupe; Gonzalez-Cozatl, Francisco X; Suzán, Gerardo; Schountz, Tony; González-Padrón, Shiara; Vigueras, Ana; Rubio, André V; Maikis, Troy J; Westrich, Bradford J; Martinez, Jose A; Esteve-Gassent, Maria D; Torres, Madison; Rodriguez-Ruiz, Erick R; Hahn, Dittmar; Lacher, Thomas E

2017-12-15

Recent models suggest a relationship exists between community diversity and pathogen prevalence, the proportion of individuals in a population that are infected by a pathogen, with most inferences tied to assemblage structure. Two contrasting outcomes of this relationship have been proposed: the "dilution effect" and the "amplification effect." Small mammal assemblage structure in disturbed habitats often differs from assemblages in sylvan environments, and hantavirus prevalence is often negatively correlated with habitats containing high species diversity via dilution effect dynamics. As species richness increases, prevalence of infection often is decreased. However, anthropogenic changes to sylvan landscapes have been shown to decrease species richness and/or increase phylogenetic similarities within assemblages. Between January 2011 and January 2016, we captured and tested 2406 individual small mammals for hantavirus antibodies at 20 sites across Texas and México and compared differences in hantavirus seroprevalence, species composition, and assemblage structure between sylvan and disturbed habitats. We found 313 small mammals positive for antibodies against hantaviruses, evincing an overall prevalence of 9.7% across all sites. In total, 40 species of small mammals were identified comprising 2 taxonomic orders (Rodentia and Eulipotyphla). By sampling both habitat types concurrently, we were able to make real-world inferences into the efficacy of dilution effect theory in terms of hantavirus ecology. Our hypothesis predicting greater species richness higher in sylvan habitats compared to disturbed areas was not supported, suggesting the characteristics of assemblage structure do not adhere to current conceptions of species richness negatively influencing prevalence via a dilution effect.

Acute bacterial and viral meningitis.

PubMed

Bartt, Russell

2012-12-01

Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

MHC standing genetic variation and pathogen resistance in wild Atlantic salmon

PubMed Central

Dionne, Mélanie; Miller, Kristina M.; Dodson, Julian J.; Bernatchez, Louis

2009-01-01

Pathogens are increasingly emerging in human-altered environments as a serious threat to biodiversity. In this context of rapid environmental changes, improving our knowledge on the interaction between ecology and evolution is critical. The objective of this study was to evaluate the influence of an immunocompetence gene, the major histocompatibility complex (MHC) class IIβ, on the pathogen infection levels in wild Atlantic salmon populations, Salmo salar, and identify selective agents involved in contemporary coevolution. MHC variability and bacterial infection rate were determined throughout the summer in juvenile salmon from six rivers belonging to different genetic and ecological regions in Québec, Canada. A total of 13 different pathogens were identified in kidney by DNA sequence analysis, including a predominant myxozoa, most probably recently introduced in North America. Infection rates were the highest in southern rivers at the beginning of the summer (average 47.6±6.3% infected fish). One MHC allele conferred a 2.9 times greater chance of being resistant to myxozoa, while another allele increased susceptibility by 3.4 times. The decrease in frequency of the susceptibility allele but not other MHC or microsatellite alleles during summer was suggestive of a mortality event from myxozoa infection. These results supported the hypothesis of pathogen-driven selection in the wild by means of frequency-dependent selection or change in selection through time and space rather than heterozygous advantage, and underline the importance of MHC standing genetic variation for facing pathogens in a changing environment. PMID:19414470

Quantitative multiplex detection of pathogen biomarkers

DOEpatents

Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I.; Martinez, Jennifer; Grace, Wynne K.

2016-02-09

The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

Quantitative multiplex detection of pathogen biomarkers

DOEpatents

Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I; Martinez, Jennifer; Grace, Wynne K

2014-10-14

The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

A review of Eimeria infections in horses and other equids

USDA-ARS?s Scientific Manuscript database

There is considerable confusion concerning validity of Eimeria species in equids, and endogenous developmental stages and pathogenicity of equid Eimeria. This paper summarizes worldwide information on history, structure, life cycle, pathogenicity, prevalence, epidemiology, and diagnosis of Eimeria i...

Pathogenic Serum Amyloid A 1.1 Shows a Long Oligomer-rich Fibrillation Lag Phase Contrary to the Highly Amyloidogenic Non-pathogenic SAA2.2*

PubMed Central

Srinivasan, Saipraveen; Patke, Sanket; Wang, Yun; Ye, Zhuqiu; Litt, Jeffrey; Srivastava, Sunit K.; Lopez, Maria M.; Kurouski, Dmitry; Lednev, Igor K.; Kane, Ravi S.; Colón, Wilfredo

2013-01-01

Serum amyloid A (SAA) is best known for being the main component of amyloid in the inflammation-related disease amyloid A (AA) amyloidosis. Despite the high sequence identity among different SAA isoforms, not all SAA proteins are pathogenic. In most mouse strains, the AA deposits mostly consist of SAA1.1. Conversely, the CE/J type mouse expresses a single non-pathogenic SAA2.2 protein that is 94% identical to SAA1.1. Here we show that SAA1.1 and SAA2.2 differ in their quaternary structure, fibrillation kinetics, prefibrillar oligomers, and fibril morphology. At 37 °C and inflammation-related SAA concentrations, SAA1.1 exhibits an oligomer-rich fibrillation lag phase of a few days, whereas SAA2.2 shows virtually no lag phase and forms small fibrils within a few hours. Deep UV resonance Raman, far UV-circular dichroism, atomic force microscopy, and fibrillation cross-seeding experiments suggest that SAA1.1 and SAA2.2 fibrils possess different morphology. Both the long-lived oligomers of pathogenic SAA1.1 and the fleeting prefibrillar oligomers of non-pathogenic SAA2.2, but not their respective amyloid fibrils, permeabilized synthetic bilayer membranes in vitro. This study represents the first comprehensive comparison between the biophysical properties of SAA isoforms with distinct pathogenicities, and the results suggest that structural and kinetic differences in the oligomerization-fibrillation of SAA1.1 and SAA2.2, more than their intrinsic amyloidogenicity, may contribute to their diverse pathogenicity. PMID:23223242

Changes in the intraisolate genetic structure of Beet necrotic yellow vein virus populations associated with plant resistance breakdown.

PubMed

Acosta-Leal, Rodolfo; Fawley, Marvin W; Rush, Charles M

2008-06-20

The causal agent of rhizomania disease, Beet necrotic yellow vein virus (BNYVV), typically produces asymptomatic root-limited infections in sugar beets (Beta vulgaris) carrying the Rz1-allele. Unfortunately, this dominant resistance has been recently overcome. Multiple cDNA clones of the viral pathogenic determinant p25, derived from populations infecting susceptible or resistant plants, were sequenced to identify host effects on the viral population structure. Populations isolated from compatible plant-virus interactions (susceptible plant-wild type virus and resistant plant-resistant breaking variants) were large and relatively homogeneous, whereas those from the incompatible interaction (resistant plant-avirulent type virus) were small and highly heterogeneous. All populations from susceptible plants had the same dominant haplotype, whereas those from resistant cultivars had a different haplotype surrounded by a spectrum of mutants. Selection and diversification analyses suggest an evolutionary trajectory of BNYVV with positive selection for changes required to overcome resistance, followed by elimination of hitchhiking mutations through purifying selection.

Cell-autonomous defense, re-organization and trafficking of membranes in plant-microbe interactions.

PubMed

Dörmann, Peter; Kim, Hyeran; Ott, Thomas; Schulze-Lefert, Paul; Trujillo, Marco; Wewer, Vera; Hückelhoven, Ralph

2014-12-01

Plant cells dynamically change their architecture and molecular composition following encounters with beneficial or parasitic microbes, a process referred to as host cell reprogramming. Cell-autonomous defense reactions are typically polarized to the plant cell periphery underneath microbial contact sites, including de novo cell wall biosynthesis. Alternatively, host cell reprogramming converges in the biogenesis of membrane-enveloped compartments for accommodation of beneficial bacteria or invasive infection structures of filamentous microbes. Recent advances have revealed that, in response to microbial encounters, plasma membrane symmetry is broken, membrane tethering and SNARE complexes are recruited, lipid composition changes and plasma membrane-to-cytoskeleton signaling is activated, either for pre-invasive defense or for microbial entry. We provide a critical appraisal on recent studies with a focus on how plant cells re-structure membranes and the associated cytoskeleton in interactions with microbial pathogens, nitrogen-fixing rhizobia and mycorrhiza fungi. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

A fungal pathogen of amphibians, Batrachochytrium dendrobatidis, attenuates in pathogenicity with in vitro passages.

PubMed

Langhammer, Penny F; Lips, Karen R; Burrowes, Patricia A; Tunstall, Tate; Palmer, Crystal M; Collins, James P

2013-01-01

Laboratory investigations into the amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), have accelerated recently, given the pathogen's role in causing the global decline and extinction of amphibians. Studies in which host animals were exposed to Bd have largely assumed that lab-maintained pathogen cultures retained the infective and pathogenic properties of wild isolates. Attenuated pathogenicity is common in artificially maintained cultures of other pathogenic fungi, but to date, it is unknown whether, and to what degree, Bd might change in culture. We compared zoospore production over time in two samples of a single Bd isolate having different passage histories: one maintained in artificial media for more than six years (JEL427-P39), and one recently thawed from cryopreserved stock (JEL427-P9). In a common garden experiment, we then exposed two different amphibian species, Eleutherodactylus coqui and Atelopus zeteki, to both cultures to test whether Bd attenuates in pathogenicity with in vitro passages. The culture with the shorter passage history, JEL427-P9, had significantly greater zoospore densities over time compared to JEL427-P39. This difference in zoospore production was associated with a difference in pathogenicity for a susceptible amphibian species, indicating that fecundity may be an important virulence factor for Bd. In the 130-day experiment, Atelopus zeteki frogs exposed to the JEL427-P9 culture experienced higher average infection intensity and 100% mortality, compared with 60% mortality for frogs exposed to JEL427-P39. This effect was not observed with Eleutherodactylus coqui, which was able to clear infection. We hypothesize that the differences in phenotypic performance observed with Atelopus zeteki are rooted in changes of the Bd genome. Future investigations enabled by this study will focus on the underlying mechanisms of Bd pathogenicity.

Molecular basis of viral and microbial pathogenesis

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

Rott, R.; Goebel, W.

1988-01-01

The contents of this book are: Correlation Between Viroid Structure and Pathogenicty; Antigenicity of the Influenza Haemagglutinia Membrane Glycoprotein; Viral Glycoproteins as Determinants of Pathogenicity; Virus Genes Involved in Host Range and Pathogenicity; Molecular Heterogenetiy of Pathogenic Herpus Viruses; Recombination of Foreign (Viral) DNA with Host Genome: Studies in Vivo and in a Cell-Free system; Disorders of Cellular Neuro-Functions by Persistent Viral Infection; Pathogenic Aspects of Measles Virus-Persistent Infections in Man; Analysis of the Dual Lineage Specificity of E26 Avian Leukemia Virus; Mx Gene Control of Influenza Virus Susceptibility; Shiga and Shika-Like Toxins: A Family of Related Cytokinons; and Molecularmore » Mechanisms of Pathogenicity in Shigella Flexneri.« less

Extending the the behavioral immune system to political psychology: are political conservatism and disgust sensitivity really related?

PubMed

Tybur, Joshua M; Merriman, Leslie A; Hooper, Ann E Caldwell; McDonald, Melissa M; Navarrete, Carlos David

2010-10-26

Previous research suggests that several individual and cultural level attitudes, cognitions, and societal structures may have evolved to mitigate the pathogen threats posed by intergroup interactions. It has been suggested that these anti-pathogen defenses are at the root of conservative political ideology. Here, we test a hypothesis that political conservatism functions as a pathogen-avoidance strategy. Across three studies, we consistently find no relationship between sensitivity to pathogen disgust and multiple measures of political conservatism. These results are contrasted with theoretical perspectives suggesting a relationship between conservatism and pathogen avoidance, and with previous findings of a relationship between conservatism and disgust sensitivity.

Arachidonic Acid: An Evolutionarily Conserved Signaling Molecule Modulates Plant Stress Signaling Networks[C][W

PubMed Central

Savchenko, Tatyana; Walley, Justin W.; Chehab, E. Wassim; Xiao, Yanmei; Kaspi, Roy; Pye, Matthew F.; Mohamed, Maged E.; Lazarus, Colin M.; Bostock, Richard M.; Dehesh, Katayoon

2010-01-01

Fatty acid structure affects cellular activities through changes in membrane lipid composition and the generation of a diversity of bioactive derivatives. Eicosapolyenoic acids are released into plants upon infection by oomycete pathogens, suggesting they may elicit plant defenses. We exploited transgenic Arabidopsis thaliana plants (designated EP) producing eicosadienoic, eicosatrienoic, and arachidonic acid (AA), aimed at mimicking pathogen release of these compounds. We also examined their effect on biotic stress resistance by challenging EP plants with fungal, oomycete, and bacterial pathogens and an insect pest. EP plants exhibited enhanced resistance to all biotic challenges, except they were more susceptible to bacteria than the wild type. Levels of jasmonic acid (JA) were elevated and levels of salicylic acid (SA) were reduced in EP plants. Altered expression of JA and SA pathway genes in EP plants shows that eicosapolyenoic acids effectively modulate stress-responsive transcriptional networks. Exogenous application of various fatty acids to wild-type and JA-deficient mutants confirmed AA as the signaling molecule. Moreover, AA treatment elicited heightened expression of general stress-responsive genes. Importantly, tomato (Solanum lycopersicum) leaves treated with AA exhibited reduced susceptibility to Botrytis cinerea infection, confirming AA signaling in other plants. These studies support the role of AA, an ancient metazoan signaling molecule, in eliciting plant stress and defense signaling networks. PMID:20935246

Genetic and bioinformatics analysis of four novel GCK missense variants detected in Caucasian families with GCK-MODY phenotype.

PubMed

Costantini, S; Malerba, G; Contreas, G; Corradi, M; Marin Vargas, S P; Giorgetti, A; Maffeis, C

2015-05-01

Heterozygous loss-of-function mutations in the glucokinase (GCK) gene cause maturity-onset diabetes of the young (MODY) subtype GCK (GCK-MODY/MODY2). GCK sequencing revealed 16 distinct mutations (13 missense, 1 nonsense, 1 splice site, and 1 frameshift-deletion) co-segregating with hyperglycaemia in 23 GCK-MODY families. Four missense substitutions (c.718A>G/p.Asn240Asp, c.757G>T/p.Val253Phe, c.872A>C/p.Lys291Thr, and c.1151C>T/p.Ala384Val) were novel and a founder effect for the nonsense mutation (c.76C>T/p.Gln26*) was supposed. We tested whether an accurate bioinformatics approach could strengthen family-genetic evidence for missense variant pathogenicity in routine diagnostics, where wet-lab functional assays are generally unviable. In silico analyses of the novel missense variants, including orthologous sequence conservation, amino acid substitution (AAS)-pathogenicity predictors, structural modeling and splicing predictors, suggested that the AASs and/or the underlying nucleotide changes are likely to be pathogenic. This study shows how a careful bioinformatics analysis could provide effective suggestions to help molecular-genetic diagnosis in absence of wet-lab validations. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mycelial growth rate and toxin production in the seed pathogen Pyrenophora semeniperda: Resource trade-offs and temporally varying selection

Treesearch

S. E. Meyer; M. Masi; S. Clement; T. L. Davis; J. Beckstead

2015-01-01

Pyrenophora semeniperda, an important pathogen in Bromus tectorum seed banks in semi-arid western North America, exhibits >4-fold variation in mycelial growth rate. Host seeds exhibit seasonal changes in dormancy that affect the risk of pathogen-caused mortality. The hypothesis tested is that contrasting seed dormancy phenotypes select for contrasting strategies...

Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

PubMed Central

Shinoda, Kenta; Hirahara, Kiyoshi; Iinuma, Tomohisa; Ichikawa, Tomomi; Suzuki, Akane S.; Sugaya, Kaoru; Tumes, Damon J.; Yamamoto, Heizaburo; Hara, Takahiro; Tani-ichi, Shizue; Ikuta, Koichi; Okamoto, Yoshitaka; Nakayama, Toshinori

2016-01-01

Memory CD4+ T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1+IL-7–producing lymphatic endothelial cells (LECs). The Thy1+IL-7–producing LECs express IL-33 and T-cell–attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4+ T cells and IL-7+IL-33+ LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1+IL-7–producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells. PMID:27140620

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

AMP-activated Protein Kinase As a Target For Pathogens: Friends Or Foes?

PubMed

Moreira, Diana; Silvestre, Ricardo; Cordeiro-da-Silva, Anabela; Estaquier, Jérôme; Foretz, Marc; Viollet, Benoit

2016-01-01

Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we highlight recent advances showing the importance of AMPK signaling in pathogen-host interactions. Pathogens interact with AMPK by a variety of mechanisms aimed at reprogramming host cell metabolism to their own benefit. Stimulation of AMPK activity provides an efficient process to rapidly adapt pathogen metabolism to the major nutritional changes often encountered during the different phases of infection. However, inhibition of AMPK is also used by pathogens to manipulate innate host response, indicating that AMPK appears relevant to restriction of pathogen infection. We also document the effects of pharmacological AMPK modulators on pathogen proliferation and survival. This review illustrates intricate pathogen-AMPK interactions that may be exploited to the development of novel anti-pathogen therapies.

AMP-activated protein kinase as a target for pathogens: friends or foes?

PubMed Central

Moreira, Diana; Silvestre, Ricardo; Cordeiro-Da-Silva, Anabela; Estaquier, Jérôme; Foretz, Marc; Viollet, Benoit

2016-01-01

Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we highlight recent advances showing the importance of AMPK signaling in pathogen-host interactions. Pathogens interact with AMPK by a variety of mechanisms aimed at reprogramming host cell metabolism to their own benefit. Stimulation of AMPK activity provides an efficient process to rapidly adapt pathogen metabolism to the major nutritional changes often encountered during the different phases of infection. However, inhibition of AMPK is also used by pathogens to manipulate innate host response, indicating that AMPK appears relevant to restriction of pathogen infection. We also document the effects of pharmacological AMPK modulators on pathogen proliferation and survival. This review illustrates intricate pathogen-AMPK interactions that maybe exploited to the development of novel anti-pathogen therapies. PMID:25882224

Evidence for Ecological Flexibility in the Cosmopolitan Genus Curtobacterium

DOE PAGES

Chase, Alexander B.; Arevalo, Philip; Polz, Martin F.; ...

2016-11-22

Assigning ecological roles to bacterial taxa remains imperative to understanding how microbial communities will respond to changing environmental conditions. Here we analyze the genus Curtobacterium, as it was found to be the most abundant taxon in a leaf litter community in southern California. Traditional characterization of this taxon predominantly associates it as the causal pathogen in the agricultural crops of dry beans. Therefore, we sought to investigate whether the abundance of this genus was because of its role as a plant pathogen or another ecological role. By collating >24,000 16S rRNA sequences with 120 genomes across the Microbacteriaceae family, wemore » show that Curtobacterium has a global distribution with a predominant presence in soil ecosystems. Moreover, this genus harbors a high diversity of genomic potential for the degradation of carbohydrates, specifically with regards to structural polysaccharides. We conclude that Curtobacterium may be responsible for the degradation of organic matter within litter communities.« less

Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.

PubMed

van Eyk, Clare L; O'Keefe, Louise V; Lawlor, Kynan T; Samaraweera, Saumya E; McLeod, Catherine J; Price, Gareth R; Venter, Deon J; Richards, Robert I

2011-07-15

Recent evidence supports a role for RNA as a common pathogenic agent in both the 'polyglutamine' and 'untranslated' dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin-forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcript levels as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease-associated repeat sequences--CAG, CUG and AUUCU--were specifically expressed in the neurons of Drosophila and resultant common transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3-β signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.

Evaluation of dose dependent antimicrobial activity of self-assembled chitosan, nano silver and chitosan-nano silver composite against several pathogens.

PubMed

Tareq, Foysal Kabir; Fayzunnesa, Mst; Kabir, Md Shahariar; Nuzat, Musrat

2018-01-01

The aim of this investigation to preparation of silver nanoparticles organized chitosan nano polymer, which effective against microbial and pathogens, when apply to liquid medium and edible food products surface, will rescue the growth of microbes. Self-assembly approach used to synthesis of silver nanoparticles and silver nanoparticles organized chitosan nano polymer. Silver nanoparticles and silver nanoparticles organized chitosan nano polymer and film characterized using Ultra-violate visible spectrometer (UV-vis), X-ray diffraction (X-ray), and Scanning electronic microscope (SEM). The crystalline structured protein capped nano silver successfully synthesized at range of 12 nm-29 nm and organized into chitosan nano polymer. Antimicrobial ingredient in liquid medium and food product surface provide to rescue oxidative change and growth of microorganism to provide higher safety. The silver nanoparticles organized chitosan nano polymer caused the death of microorganism. The materials in nano scale synthesized successfully using self-assembly method, which showed good antimicrobial properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Situated knowledge of pathogenic landscapes in Ghana: Understanding the emergence of Buruli ulcer through qualitative analysis.

PubMed

Tschakert, Petra; Ricciardi, Vincent; Smithwick, Erica; Machado, Mario; Ferring, David; Hausermann, Heidi; Bug, Leah

2016-02-01

Successfully addressing neglected tropical diseases requires nuanced understandings of pathogenic landscapes that incorporate situated, contexualized community knowledge. In the case of Buruli ulcer (BU), the role of social science is vital to investigate complex human-environment interactions and navigate different ways of knowing. We analyze a set of qualitative data from our interdisciplinary project on BU in Ghana, drawing from participatory mapping, focus group discussions, semi-structured interviews, and open-ended survey questions to explore how people in endemic and non-endemic areas see themselves embedded in changing environmental and social landscapes. We pay particular attention to landscape disturbance through logging and small-scale alluvial gold mining. The results from our participatory research underscore the holistic nature of BU emergence in landscapes, encapsulated in partial and incomplete local descriptions, the relevance of collective learning to distill complexity, and the potential of rich qualitative data to inform quantitative landscape-disease models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

PubMed Central

Eyal, Zohar; Matzov, Donna; Krupkin, Miri; Wekselman, Itai; Paukner, Susanne; Zimmerman, Ella; Rozenberg, Haim; Bashan, Anat; Yonath, Ada

2015-01-01

The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid and telithromycin, as well as with a new, highly potent pleuromutilin derivative, BC-3205. These crystal structures shed light on specific structural motifs of the S. aureus ribosome and the binding modes of the aforementioned antibiotics. Moreover, by analyzing the ribosome structure and comparing it with those of nonpathogenic bacterial models, we identified some unique internal and peripheral structural motifs that may be potential candidates for improving known antibiotics and for use in the design of selective antibiotic drugs against S. aureus. PMID:26464510

Structure and temporal dynamics of the bacterial communities associated to microhabitats of the coral Oculina patagonica.

PubMed

Rubio-Portillo, Esther; Santos, Fernando; Martínez-García, Manuel; de Los Ríos, Asunción; Ascaso, Carmen; Souza-Egipsy, Virginia; Ramos-Esplá, Alfonso A; Anton, Josefa

2016-12-01

Corals are known to contain a diverse microbiota that plays a paramount role in the physiology and health of holobiont. However, few studies have addressed the variability of bacterial communities within the coral host. In this study, bacterial community composition from the mucus, tissue and skeleton of the scleractinian coral Oculina patagonica were investigated seasonally at two locations in the Western Mediterranean Sea, to further understand how environmental conditions and the coral microbiome structure are related. We used denaturing gradient gel electrophoresis in combination with next-generation sequencing and electron microscopy to characterize the bacterial community. The bacterial communities were significantly different among coral compartments, and coral tissue displayed the greatest changes related to environmental conditions and coral health status. Species belonging to the Rhodobacteraceae and Vibrionaceae families form part of O. patagonica tissues core microbiome and may play significant roles in the nitrogen cycle. Furthermore, sequences related to the coral pathogens, Vibrio mediterranei and Vibrio coralliilyticus, were detected not only in bleached corals but also in healthy ones, even during cold months. This fact opens a new view onto unveiling the role of pathogens in the development of coral diseases in the future. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Identification of capsule, biofilm, lateral flagellum, and type IV pili in Vibrio mimicus strains.

PubMed

Tercero-Alburo, J J; González-Márquez, H; Bonilla-González, E; Quiñones-Ramírez, E I; Vázquez-Salinas, C

2014-11-01

Vibrio mimicus is a bacterium that causes gastroenteritis; it is closely related to Vibrio cholerae, and can cause acute diarrhea like cholera- or dysentery-type diarrhea. It is distributed worldwide. Factors associated with virulence (such as hemolysins, enterotoxins, proteases, phospholipases, aerobactin, and hemagglutinin) have been identified; however, its pathogenicity mechanism is still unknown. In pathogenic Vibrio species such as V. cholerae, Vibrio. parahaemolyticus and Vibrio vulnificus, capsule, biofilms, lateral flagellum, and type IV pili are structures described as essential for pathogenicity. These structures had not been described in V. mimicus until this work. We used 20 V. mimicus strains isolated from water (6), oyster (9), and fish (5) samples and we were able to identify the capsule, biofilm, lateral flagellum, and type IV pili through phenotypic tests, electron microscopy, PCR, and sequencing. In all tested strains, we observed and identified the presence of capsular exopolysaccharide, biofilm formation in an in vitro model, as well as swarming, multiple flagellation, and pili. In addition, we identified homologous genes to those described in other bacteria of the genus in which these structures have been found. Identification of these structures in V. mimicus is a contribution to the biology of this organism and can help to reveal its pathogenic behavior. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic structure of the fungal grapevine pathogen Eutypa lata from four continents

USDA-ARS?s Scientific Manuscript database

Deciphering the geographic origins of pathogens and elucidating the population biology of these microscopic organisms are necessary steps to establish effective disease-control strategies. The generalist ascomycete fungus Eutypa lata causes Eutypa dieback of grapevine (Vitis vinifera) worldwide. To ...

Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes.

PubMed

Beres, Stephen B; Kachroo, Priyanka; Nasser, Waleed; Olsen, Randall J; Zhu, Luchang; Flores, Anthony R; de la Riva, Ivan; Paez-Mayorga, Jesus; Jimenez, Francisco E; Cantu, Concepcion; Vuopio, Jaana; Jalava, Jari; Kristinsson, Karl G; Gottfredsson, Magnus; Corander, Jukka; Fittipaldi, Nahuel; Di Luca, Maria Chiara; Petrelli, Dezemona; Vitali, Luca A; Raiford, Annessa; Jenkins, Leslie; Musser, James M

2016-05-31

For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease. Copyright © 2016 Beres et al.

Knowledge Mapping for Climate Change and Food- and Waterborne Diseases.

PubMed

Semenza, Jan C; Höuser, Christoph; Herbst, Susanne; Rechenburg, Andrea; Suk, Jonathan E; Frechen, Tobias; Kistemann, Thomas

2012-02-01

The authors extracted from the PubMed and ScienceDirect bibliographic databases all articles published between 1998 and 2009 that were relevant to climate change and food- and waterborne diseases. Any material within each article that provided information about a relevant pathogen and its relationship with climate and climate change was summarized as a key fact, entered into a relational knowledge base, and tagged with the terminology (predefined terms) used in the field. These terms were organized, quantified, and mapped according to predefined hierarchical categories. For noncholera Vibrio sp. and Cryptosporidium sp., data on climatic and environmental influences (52% and 49% of the total number of key facts, respectively) pertained to specific weather phenomena (as opposed to climate change phenomena) and environmental determinants, whereas information on the potential effects of food-related determinants that might be related to climate or climate change were virtually absent. This proportion was lower for the other pathogens studied ( Campylobacter sp. 40%, Salmonella sp. 27%, Norovirus 25%, Listeria sp. 8%), but they all displayed a distinct concentration of information on general food-and water-related determinants or effects, albeit with little detail. Almost no information was available concerning the potential effects of changes in climatic variables on the pathogens evaluated, such as changes in air or water temperature, precipitation, humidity, UV radiation, wind, cloud coverage, sunshine hours, or seasonality. Frequency profiles revealed an abundance of data on weather and food-specific determinants, but also exposed extensive data deficiencies, particularly with regard to the potential effects of climate change on the pathogens evaluated. A reprioritization of public health research is warranted to ensure that funding is dedicated to explicitly studying the effects of changes in climate variables on food- and waterborne diseases.

Knowledge Mapping for Climate Change and Food- and Waterborne Diseases

PubMed Central

Semenza, Jan C.; Höuser, Christoph; Herbst, Susanne; Rechenburg, Andrea; Suk, Jonathan E.; Frechen, Tobias; Kistemann, Thomas

2011-01-01

The authors extracted from the PubMed and ScienceDirect bibliographic databases all articles published between 1998 and 2009 that were relevant to climate change and food- and waterborne diseases. Any material within each article that provided information about a relevant pathogen and its relationship with climate and climate change was summarized as a key fact, entered into a relational knowledge base, and tagged with the terminology (predefined terms) used in the field. These terms were organized, quantified, and mapped according to predefined hierarchical categories. For noncholera Vibrio sp. and Cryptosporidium sp., data on climatic and environmental influences (52% and 49% of the total number of key facts, respectively) pertained to specific weather phenomena (as opposed to climate change phenomena) and environmental determinants, whereas information on the potential effects of food-related determinants that might be related to climate or climate change were virtually absent. This proportion was lower for the other pathogens studied (Campylobacter sp. 40%, Salmonella sp. 27%, Norovirus 25%, Listeria sp. 8%), but they all displayed a distinct concentration of information on general food-and water-related determinants or effects, albeit with little detail. Almost no information was available concerning the potential effects of changes in climatic variables on the pathogens evaluated, such as changes in air or water temperature, precipitation, humidity, UV radiation, wind, cloud coverage, sunshine hours, or seasonality. Frequency profiles revealed an abundance of data on weather and food-specific determinants, but also exposed extensive data deficiencies, particularly with regard to the potential effects of climate change on the pathogens evaluated. A reprioritization of public health research is warranted to ensure that funding is dedicated to explicitly studying the effects of changes in climate variables on food- and waterborne diseases. PMID:24771989

The structure of the Brassica napus seed microbiome is cultivar-dependent and affects the interactions of symbionts and pathogens.

PubMed

Rybakova, Daria; Mancinelli, Riccardo; Wikström, Mariann; Birch-Jensen, Ann-Sofie; Postma, Joeke; Ehlers, Ralf-Udo; Goertz, Simon; Berg, Gabriele

2017-09-01

Although the plant microbiome is crucial for plant health, little is known about the significance of the seed microbiome. Here, we studied indigenous bacterial communities associated with the seeds in different cultivars of oilseed rape and their interactions with symbiotic and pathogenic microorganisms. We found a high bacterial diversity expressed by tight bacterial co-occurrence networks within the rape seed microbiome, as identified by llumina MiSeq amplicon sequencing. In total, 8362 operational taxonomic units (OTUs) of 40 bacterial phyla with a predominance of Proteobacteria (56%) were found. The three cultivars that were analyzed shared only one third of the OTUs. The shared core of OTUs consisted mainly of Alphaproteobacteria (33%). Each cultivar was characterized by having its own unique bacterial structure, diversity, and proportion of unique microorganisms (25%). The cultivar with the lowest bacterial abundance, diversity, and the highest predicted bacterial metabolic activity rate contained the highest abundance of potential pathogens within the seed. This data corresponded with the observation that seedlings belonging to this cultivar responded more strongly to the seed treatments with bacterial inoculants than other cultivars. Cultivars containing higher indigenous diversity were characterized as having a higher colonization resistance against beneficial and pathogenic microorganisms. Our results were confirmed by microscopic images of the seed microbiota. The structure of the seed microbiome is an important factor in the development of colonization resistance against pathogens. It also has a strong influence on the response of seedlings to biological seed treatments. These novel insights into seed microbiome structure will enable the development of next generation strategies combining both biocontrol and breeding approaches to address world agricultural challenges.

Pathogenicity of Human ST23 Streptococcus agalactiae to Fish and Genomic Comparison of Pathogenic and Non-pathogenic Isolates.

PubMed

Wang, Rui; Li, Liping; Huang, Yin; Huang, Ting; Tang, Jiayou; Xie, Ting; Lei, Aiying; Luo, Fuguang; Li, Jian; Huang, Yan; Shi, Yunliang; Wang, Dongying; Chen, Ming; Mi, Qiang; Huang, Weiyi

2017-01-01

Streptococcus agalactiae , or Group B Streptococcus (GBS), is a major pathogen causing neonatal sepsis and meningitis, bovine mastitis, and fish meningoencephalitis. CC23, including its namesake ST23, is not only the predominant GBS strain derived from human and cattle, but also can infect a variety of homeothermic and poikilothermic species. However, it has never been characterized in fish. This study aimed to determine the pathogenicity of ST23 GBS to fish and explore the mechanisms causing the difference in the pathogenicity of ST23 GBS based on the genome analysis. Infection of tilapia with 10 human-derived ST23 GBS isolates caused tissue damage and the distribution of pathogens within tissues. The mortality rate of infection was ranged from 76 to 100%, and it was shown that the mortality rate caused by only three human isolates had statistically significant difference compared with fish-derived ST7 strain ( P < 0.05), whereas the mortality caused by other seven human isolates did not show significant difference compared with fish-derived ST7 strain. The genome comparison and prophage analysis showed that the major genome difference between virulent and non-virulent ST23 GBS was attributed to the different prophage sequences. The prophage in the P1 region contained about 43% GC and encoded 28-39 proteins, which can mediate the acquisition of YafQ/DinJ structure for GBS by phage recombination. YafQ/DinJ belongs to one of the bacterial toxin-antitoxin (TA) systems and allows cells to cope with stress. The ST23 GBS strains carrying this prophage were not pathogenic to tilapia, but the strains without the prophage or carrying the pophage that had gene mutation or deletion, especially the deletion of YafQ/DinJ structure, were highly pathogenic to tilapia. In conclusion, human ST23 GBS is highly pathogenic to fish, which may be related to the phage recombination.

Pathogenicity of Human ST23 Streptococcus agalactiae to Fish and Genomic Comparison of Pathogenic and Non-pathogenic Isolates

PubMed Central

Wang, Rui; Li, Liping; Huang, Yin; Huang, Ting; Tang, Jiayou; Xie, Ting; Lei, Aiying; Luo, Fuguang; Li, Jian; Huang, Yan; Shi, Yunliang; Wang, Dongying; Chen, Ming; Mi, Qiang; Huang, Weiyi

2017-01-01

Streptococcus agalactiae, or Group B Streptococcus (GBS), is a major pathogen causing neonatal sepsis and meningitis, bovine mastitis, and fish meningoencephalitis. CC23, including its namesake ST23, is not only the predominant GBS strain derived from human and cattle, but also can infect a variety of homeothermic and poikilothermic species. However, it has never been characterized in fish. This study aimed to determine the pathogenicity of ST23 GBS to fish and explore the mechanisms causing the difference in the pathogenicity of ST23 GBS based on the genome analysis. Infection of tilapia with 10 human-derived ST23 GBS isolates caused tissue damage and the distribution of pathogens within tissues. The mortality rate of infection was ranged from 76 to 100%, and it was shown that the mortality rate caused by only three human isolates had statistically significant difference compared with fish-derived ST7 strain (P < 0.05), whereas the mortality caused by other seven human isolates did not show significant difference compared with fish-derived ST7 strain. The genome comparison and prophage analysis showed that the major genome difference between virulent and non-virulent ST23 GBS was attributed to the different prophage sequences. The prophage in the P1 region contained about 43% GC and encoded 28–39 proteins, which can mediate the acquisition of YafQ/DinJ structure for GBS by phage recombination. YafQ/DinJ belongs to one of the bacterial toxin–antitoxin (TA) systems and allows cells to cope with stress. The ST23 GBS strains carrying this prophage were not pathogenic to tilapia, but the strains without the prophage or carrying the pophage that had gene mutation or deletion, especially the deletion of YafQ/DinJ structure, were highly pathogenic to tilapia. In conclusion, human ST23 GBS is highly pathogenic to fish, which may be related to the phage recombination. PMID:29056932

Challenges and Strategies for Breeding Resistance in Capsicum annuum to the Multifarious Pathogen, Phytophthora capsici

PubMed Central

Barchenger, Derek W.; Lamour, Kurt H.; Bosland, Paul W.

2018-01-01

Phytophthora capsici is the most devastating pathogen for chile pepper production worldwide and current management strategies are not effective. The population structure of the pathogen is highly variable and few sources of widely applicable host resistance have been identified. Recent genomic advancements in the host and the pathogen provide important insights into the difficulties reported by epidemiological and physiological studies published over the past century. This review highlights important challenges unique to this complex pathosystem and suggests strategies for resistance breeding to help limit losses associated with P. capsici. PMID:29868083

Association and Host Selectivity in Multi-Host Pathogens

PubMed Central

Malpica, José M.; Sacristán, Soledad; Fraile, Aurora; García-Arenal, Fernando

2006-01-01

The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens. PMID:17183670

Capsules from pathogenic and non-pathogenic Cryptococcus spp. manifest significant differences in structure and ability to protect against phagocytic cells.

PubMed

Araujo, Glauber de S; Fonseca, Fernanda L; Pontes, Bruno; Torres, Andre; Cordero, Radames J B; Zancopé-Oliveira, Rosely M; Casadevall, Arturo; Viana, Nathan B; Nimrichter, Leonardo; Rodrigues, Marcio L; Garcia, Eloi S; Souza, Wanderley de; Frases, Susana

2012-01-01

Capsule production is common among bacterial species, but relatively rare in eukaryotic microorganisms. Members of the fungal Cryptococcus genus are known to produce capsules, which are major determinants of virulence in the highly pathogenic species Cryptococcus neoformans and Cryptococcus gattii. Although the lack of virulence of many species of the Cryptococcus genus can be explained solely by the lack of mammalian thermotolerance, it is uncertain whether the capsules from these organisms are comparable to those of the pathogenic cryptococci. In this study, we compared the characteristic of the capsule from the non-pathogenic environmental yeast Cryptococcus liquefaciens with that of C. neoformans. Microscopic observations revealed that C. liquefaciens has a capsule visible in India ink preparations that was also efficiently labeled by three antibodies generated to specific C. neoformans capsular antigens. Capsular polysaccharides of C. liquefaciens were incorporated onto the cell surface of acapsular C. neoformans mutant cells. Polysaccharide composition determinations in combination with confocal microscopy revealed that C. liquefaciens capsule consisted of mannose, xylose, glucose, glucuronic acid, galactose and N-acetylglucosamine. Physical chemical analysis of the C. liquefaciens polysaccharides in comparison with C. neoformans samples revealed significant differences in viscosity, elastic properties and macromolecular structure parameters of polysaccharide solutions such as rigidity, effective diameter, zeta potential and molecular mass, which nevertheless appeared to be characteristics of linear polysaccharides that also comprise capsular polysaccharide of C. neoformans. The environmental yeast, however, showed enhanced susceptibility to the antimicrobial activity of the environmental phagocytes, suggesting that the C. liquefaciens capsular components are insufficient in protecting yeast cells against killing by amoeba. These results suggest that capsular structures in pathogenic Cryptococcus species and environmental species share similar features, but also manifest significant difference that could influence their potential to virulence.

Structural and functional characterization of the recombinant thioredoxin reductase from Candida albicans as a potential target for vaccine and drug design.

PubMed

Godoy, Janine Silva Ribeiro; Kioshima, Érika Seki; Abadio, Ana Karina Rodrigues; Felipe, Maria Sueli Soares; de Freitas, Sonia Maria; Svidzinski, Terezinha Inez Estivalet

2016-05-01

The thioredoxin system plays a critical role in maintaining the cytoplasm redox state, participating in functions that are important to the cellular viability of fungi. Although functional and structural information on targets in human pathogenic fungi has been scarcely described in the literature, such studies are essential for in silico drug design and biotechnological applications. Therefore, the aims of the present study were to produce recombinant proteins of the thioredoxin system from Candida albicans and evaluate their possible use as prophylactic or alternative therapies against the most important pathogenic fungus associated with nosocomial infections. We focused on biochemical and structural analyses of recombinant thioredoxin reductase from C. albicans with His-tag (CaTrxR-His) for further biotechnology applications. Heterologous CaTrxR-His was efficiently expressed in the soluble fraction of the Escherichia coli lysate. CaTrxR-His was obtained with a high level of purity and presented specific enzymatic activity. Conformational changes of the protein were observed at different pHs and temperatures, with higher thermal stability at pH 8.0. The CaTrxR-His vaccine was shown to effectively induce high levels of CaTrxR-specific immunoglobulin G antibodies in Balb/c mice and reduce the renal fungal burden of experimental disseminated candidiasis in mice. These data may greatly impact future development strategies for vaccine and drug designs against C. albicans infection.

The Evolution of Campylobacter jejuni and Campylobacter coli

PubMed Central

Sheppard, Samuel K.; Maiden, Martin C.J.

2015-01-01

The global significance of Campylobacter jejuni and Campylobacter coli as gastrointestinal human pathogens has motivated numerous studies to characterize their population biology and evolution. These bacteria are a common component of the intestinal microbiota of numerous bird and mammal species and cause disease in humans, typically via consumption of contaminated meat products, especially poultry meat. Sequence-based molecular typing methods, such as multilocus sequence typing (MLST) and whole genome sequencing (WGS), have been instructive for understanding the epidemiology and evolution of these bacteria and how phenotypic variation relates to the high degree of genetic structuring in C. coli and C. jejuni populations. Here, we describe aspects of the relatively short history of coevolution between humans and pathogenic Campylobacter, by reviewing research investigating how mutation and lateral or horizontal gene transfer (LGT or HGT, respectively) interact to create the observed population structure. These genetic changes occur in a complex fitness landscape with divergent ecologies, including multiple host species, which can lead to rapid adaptation, for example, through frame-shift mutations that alter gene expression or the acquisition of novel genetic elements by HGT. Recombination is a particularly strong evolutionary force in Campylobacter, leading to the emergence of new lineages and even large-scale genome-wide interspecies introgression between C. jejuni and C. coli. The increasing availability of large genome datasets is enhancing understanding of Campylobacter evolution through the application of methods, such as genome-wide association studies, but MLST-derived clonal complex designations remain a useful method for describing population structure. PMID:26101080

Structural and Functional Insight of Sphingosine 1-Phosphate-Mediated Pathogenic Metabolic Reprogramming in Sickle Cell Disease.

PubMed

Sun, Kaiqi; D'Alessandro, Angelo; Ahmed, Mostafa H; Zhang, Yujin; Song, Anren; Ko, Tzu-Ping; Nemkov, Travis; Reisz, Julie A; Wu, Hongyu; Adebiyi, Morayo; Peng, Zhangzhe; Gong, Jing; Liu, Hong; Huang, Aji; Wen, Yuan Edward; Wen, Alexander Q; Berka, Vladimir; Bogdanov, Mikhail V; Abdulmalik, Osheiza; Han, Leng; Tsai, Ah-Lim; Idowu, Modupe; Juneja, Harinder S; Kellems, Rodney E; Dowhan, William; Hansen, Kirk C; Safo, Martin K; Xia, Yang

2017-11-10

Elevated sphingosine 1-phosphate (S1P) is detrimental in Sickle Cell Disease (SCD), but the mechanistic basis remains obscure. Here, we report that increased erythrocyte S1P binds to deoxygenated sickle Hb (deoxyHbS), facilitates deoxyHbS anchoring to the membrane, induces release of membrane-bound glycolytic enzymes and in turn switches glucose flux towards glycolysis relative to the pentose phosphate pathway (PPP). Suppressed PPP causes compromised glutathione homeostasis and increased oxidative stress, while enhanced glycolysis induces production of 2,3-bisphosphoglycerate (2,3-BPG) and thus increases deoxyHbS polymerization, sickling, hemolysis and disease progression. Functional studies revealed that S1P and 2,3-BPG work synergistically to decrease both HbA and HbS oxygen binding affinity. The crystal structure at 1.9 Å resolution deciphered that S1P binds to the surface of 2,3-BPG-deoxyHbA and causes additional conformation changes to the T-state Hb. Phosphate moiety of the surface bound S1P engages in a highly positive region close to α1-heme while its aliphatic chain snakes along a shallow cavity making hydrophobic interactions in the "switch region", as well as with α2-heme like a molecular "sticky tape" with the last 3-4 carbon atoms sticking out into bulk solvent. Altogether, our findings provide functional and structural bases underlying S1P-mediated pathogenic metabolic reprogramming in SCD and novel therapeutic avenues.

Community Structure of Skin Microbiome of Gulf Killifish, Fundulus grandis, Is Driven by Seasonality and Not Exposure to Oiled Sediments in a Louisiana Salt Marsh.

PubMed

Larsen, Andrea M; Bullard, Stephen A; Womble, Matthew; Arias, Covadonga R

2015-08-01

Mucus of fish skin harbors complex bacterial communities that likely contribute to fish homeostasis. When the equilibrium between the host and its external bacterial symbionts is disrupted, bacterial diversity decreases while opportunistic pathogen prevalence increases, making the onset of pathogenic bacterial infection more likely. Because of that relationship, documenting temporal and spatial microbial community changes may be predictive of fish health status. The 2010 Deepwater Horizon oil spill was a potential stressor to the Gulf of Mexico's coastal ecosystem. Ribosomal intergenic spacer analysis (RISA) and pyrosequencing were used to analyze the bacterial communities (microbiome) associated with the skin and mucus of Gulf killifish (Fundulus grandis) that were collected from oiled and non-oiled salt marsh sites in Barataria Bay, LA. Water samples and fin clips were collected to examine microbiome structure. The microbiome of Gulf killifish was significantly different from that of the surrounding water, mainly attributable to shifts in abundances of Cyanobacteria and Proteobacteria. The Gulf killifish's microbiome was dominated by Gammaproteobacteria, specifically members of Pseudomonas. No significant difference was found between microbiomes of fish collected from oiled and non-oiled sites suggesting little impact of oil contamination on fish bacterial assemblages. Conversely, seasonality significantly influenced microbiome structure. Overall, the high similarity observed between the microbiomes of individual fish observed during this study posits that skin and mucus of Gulf killifish have a resilient core microbiome.

Structural Genomics of Protein Phosphatases

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

Almo,S.; Bonanno, J.; Sauder, J.

The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS Protein Structure Initiative (PSI) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of all human protein phosphatases and protein phosphatases from biomedically-relevant pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcriptionalmore » regulation, regulation of major signaling pathways, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise to provide an unprecedented database and materials repository for structure-guided experimental and computational discovery of inhibitors for all classes of protein phosphatases.« less

A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence

PubMed Central

Morrow, Carl A.; Lee, I. Russel; Chow, Eve W. L.; Ormerod, Kate L.; Goldinger, Anita; Byrnes, Edmond J.; Nielsen, Kirsten; Heitman, Joseph; Schirra, Horst Joachim; Fraser, James A.

2012-01-01

ABSTRACT The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently diversified, forming a species complex containing members with distinct morphologies, distributions, and pathologies of infection. We have investigated structural changes in genomic architecture such as inversions and translocations that distinguish the most pathogenic variety, Cryptococcus neoformans var. grubii, from the less clinically prevalent Cryptococcus neoformans var. neoformans and Cryptococcus gattii. Synteny analysis between the genomes of the three Cryptococcus species/varieties (strains H99, JEC21, and R265) reveals that C. neoformans var. grubii possesses surprisingly few unique genomic rearrangements. All but one are relatively small and are shared by all molecular subtypes of C. neoformans var. grubii. In contrast, the large translocation peculiar to the C. neoformans var. grubii type strain is found in all tested subcultures from multiple laboratories, suggesting that it has possessed this rearrangement since its isolation from a human clinical sample. Furthermore, we find that the translocation directly disrupts two genes. The first of these encodes a novel protein involved in metabolism of glucose at human body temperature and affects intracellular levels of trehalose. The second encodes a homeodomain-containing transcription factor that modulates melanin production. Both mutations would be predicted to increase pathogenicity; however, when recreated in an alternate genetic background, these mutations do not affect virulence in animal models. The type strain of C. neoformans var. grubii in which the majority of molecular studies have been performed is therefore atypical for carbon metabolism and key virulence attributes. PMID:22375073

Climate change impact on infection risks during bathing downstream of sewage emissions from CSOs or WWTPs.

PubMed

Sterk, Ankie; de Man, Heleen; Schijven, Jack F; de Nijs, Ton; de Roda Husman, Ana Maria

2016-11-15

Climate change is expected to influence infection risks while bathing downstream of sewage emissions from combined sewage overflows (CSOs) or waste water treatment plants (WWTPs) due to changes in pathogen influx, rising temperatures and changing flow rates of the receiving waters. In this study, climate change impacts on the surface water concentrations of Campylobacter, Cryptosporidium and norovirus originating from sewage were modelled. Quantitative microbial risk assessment (QMRA) was used to assess changes in risks of infection. In general, infection risks downstream of WWTPs are higher than downstream CSOs. Even though model outputs show an increase in CSO influxes, in combination with changes in pathogen survival, dilution within the sewage system and bathing behaviour, the effects on the infection risks are limited. However, a decrease in dilution capacity of surface waters could have significant impact on the infection risks of relatively stable pathogens like Cryptosporidium and norovirus. Overall, average risks are found to be higher downstream WWTPs compared to CSOs. Especially with regard to decreased flow rates, adaptation measures on treatment at WWTPs may be more beneficial for human health than decreasing CSO events. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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...

Accelerating dynamic genetic conservation efforts: Use of FT-IR spectroscopy for the rapid identification of trees resistant to destructive pathogens

Treesearch

C. Villari; R.A. Sniezko; L.E. Rodriguez-Saona; P. Bonello

2017-01-01

A strong focus on tree germplasm that can resist threats such as non-native insects and pathogens, or a changing climate, is fundamental for successful genetic conservation efforts. However, the unavailability of tools for rapid screening of tree germplasm for resistance to critical pathogens and insect pests is becoming an increasingly serious bottleneck. Here we...

CODIFI (Concordance in Diabetic Foot Ulcer Infection): a cross-sectional study of wound swab versus tissue sampling in infected diabetic foot ulcers in England.

PubMed

Nelson, Andrea; Wright-Hughes, Alexandra; Backhouse, Michael Ross; Lipsky, Benjamin A; Nixon, Jane; Bhogal, Moninder S; Reynolds, Catherine; Brown, Sarah

2018-01-31

To determine the extent of agreement and patterns of disagreement between wound swab and tissue samples in patients with an infected diabetic foot ulcer (DFU). Multicentre, prospective, cross-sectional study. Primary and secondary care foot ulcer/diabetic outpatient clinics and hospital wards across England. Inclusion criteria: consenting patients aged ≥18 years; diabetes mellitus; suspected infected DFU. clinically inappropriate to take either sample. Wound swab obtained using Levine's technique; tissue samples collected using a sterile dermal curette or scalpel. Coprimary: reported presence, and number, of pathogens per sample; prevalence of resistance to antimicrobials among likely pathogens. Secondary: recommended change in antibiotic therapy based on blinded clinical review; adverse events; sampling costs. 400 consenting patients (79% male) from 25 centres.Most prevalent reported pathogens were Staphylococcus aureus (43.8%), Streptococcus (16.7%) and other aerobic Gram-positive cocci (70.6%). At least one potential pathogen was reported from 70.1% of wound swab and 86.1% of tissue samples. Pathogen results differed between sampling methods in 58% of patients, with more pathogens and fewer contaminants reported from tissue specimens.The majority of pathogens were reported significantly more frequently in tissue than wound swab samples (P<0.01), with equal disagreement for S. aureus and Pseudomonas aeruginosa. Blinded clinicians more often recommended a change in antibiotic regimen based on tissue compared with wound swab results (increase of 8.9%, 95% CI 2.65% to 15.3%). Ulcer pain and bleeding occurred more often after tissue collection versus wound swabs (pain: 9.3%, 1.3%; bleeding: 6.8%, 1.5%, respectively). Reports of tissue samples more frequently identified pathogens, and less frequently identified non-pathogens compared with wound swab samples. Blinded clinicians more often recommended changes in antibiotic therapy based on tissue compared with wound swab specimens. Further research is needed to determine the effect of the additional information provided by tissue samples. ISRCTN52608451. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Assessing the impact of fungicide enostroburin application on bacterial community in wheat phyllosphere.

PubMed

Gu, Likun; Bai, Zhihui; Jin, Bo; Hu, Qing; Wang, Huili; Zhuang, Guoqiang; Zhang, Hongxun

2010-01-01

Fungicides have been used extensively for controlling fungal pathogens of plants. However, little is known regarding the effects that fungicides upon the indigenous bacterial communities within the plant phyllosphere. The aims of this study were to assess the impact of fungicide enostroburin upon bacterial communities in wheat phyllosphere. Culture-independent methodologies of 16S rDNA clone library and 16S rDNA directed polymerase chain reaction with denaturing gradient gel electrophoresis (PCR-DGGE) were used for monitoring the change of bacterial community. The 16S rDNA clone library and PCR-DGGE analysis both confirmed the microbial community of wheat plant phyllosphere were predominantly of the gamma-Proteobacteria phyla. Results from PCR-DGGE analysis indicated a significant change in bacterial community structure within the phyllosphere following fungicide enostroburin application. Bands sequenced within control cultures were predominantly of Pseudomonas genus, but those bands sequenced in the treated samples were predominantly strains of Pantoea genus and Pseudomonas genus. Of interest was the appearance of two DGGE bands following fungicide treatment, one of which had sequence similarities (98%) to Pantoea sp. which might be a competitor of plant pathogens. This study revealed the wheat phyllosphere bacterial community composition and a shift in the bacterial community following fungicide enostroburin application.

[Function of rmlB in the pathogenic Escherichia coli 44277 (O2: k1)].

PubMed

Ding, Weiping; Luo, Yuanming; Ai, Guomin; Jin, Cheng

2011-09-01

To identify the role of rmlB in synthesizing L-rhamnose in the pathogenic Escherichia coli 44277 (O2:K1:H4). The rmlB gene was expressed and the activity of the recombinant protein was assayed by measuring the quantity of reaction product. The rmlB gene was deleted by homologous recombination, then phenotypic changes of the delta rmlB mutant was analyzed by Electron Microscope, Tricine SDS-PAGE and immunological methods. Further, various methods including MALDI-TOF-MS/MS, GC-MS and NMR was used to investigate the O antigen structure of the delta rmlB mutant. RmlB was confirmed to be a protein harboring the activity of dTDP-D-glucose 4,6-dehydratase through enzyme assay. The delta rmlB mutant was successfully constructed and no phenotypic change was observed after compared with the wild type strain. L-rhamnose still existed in the delta rmlB mutant, indicating that there may be isoenzyme of RmlB presenting in the mutant or there was a novel way synthesizing L-rhamnose in the mutant. RmlB has the activity of dTDP-D-glucose 4,6-dehydratase but it is not essential for the synthesis of L-rhamnose.

How the biodiversity sciences may aid biological tools and ecological engineering to assess the impact of climatic changes.

PubMed

Morand, S; Guégan, J-F

2008-08-01

This paper addresses how climate changes interact with other global changes caused by humans (habitat fragmentation, changes in land use, bioinvasions) to affect biodiversity. Changes in biodiversity at all levels (genetic, population and community) affect the functioning of ecosystems, in particular host-pathogen interactions, with major consequences in health ecology (emergence and re-emergence; the evolution of virulence and resistance). In this paper, the authors demonstrate that the biodiversity sciences, epidemiological theory and evolutionary ecology are indispensable in assessing the impact of climate changes, and also for modelling the evolution of host-pathogen interactions in a changing environment. The next step is to apply health ecology to the science of ecological engineering.

Change in the Structure of Escherichia coli Population and the Pattern of Virulence Genes along a Rural Aquatic Continuum

PubMed Central

Petit, Fabienne; Clermont, Olivier; Delannoy, Sabine; Servais, Pierre; Gourmelon, Michèle; Fach, Patrick; Oberlé, Kenny; Fournier, Matthieu; Denamur, Erick; Berthe, Thierry

2017-01-01

The aim of this study was to investigate the diversity of the Escherichia coli population, focusing on the occurrence of pathogenic E. coli, in surface water draining a rural catchment. Two sampling campaigns were carried out in similar hydrological conditions (wet period, low flow) along a river continuum, characterized by two opposite density gradients of animals (cattle and wild animals) and human populations. While the abundance of E. coli slightly increased along the river continuum, the abundance of both human and ruminant-associated Bacteroidales markers, as well as the number of E. coli multi-resistant to antibiotics, evidenced a fecal contamination originating from animals at upstream rural sites, and from humans at downstream urban sites. A strong spatial modification of the structure of the E. coli population was observed. At the upstream site close to a forest, a higher abundance of the B2 phylogroup and Escherichia clade strains were observed. At the pasture upstream site, a greater proportion of both E and B1 phylogroups was detected, therefore suggesting a fecal contamination of mainly bovine origin. Conversely, in downstream urban sites, A, D, and F phylogroups were more abundant. To assess the occurrence of intestinal pathogenic strains, virulence factors [afaD, stx1, stx2, eltB (LT), estA (ST), ipaH, bfpA, eae, aaiC and aatA] were screened among 651 E. coli isolates. Intestinal pathogenic strains STEC O174:H21 (stx2) and EHEC O26:H11 (eae, stx1) were isolated in water and sediments close to the pasture site. In contrast, in the downstream urban site aEPEC/EAEC and DAEC of human origin, as well as extra-intestinal pathogenic E. coli belonging to clonal group A of D phylogroup, were sampled. Even if the estimated input of STEC (Shiga toxin-producing E. coli) – released in water at the upstream pasture site – at the downstream site was low, we show that STEC could persist in sediment. These results show that, the run-off of small cattle farms contributed, as much as the wastewater effluent, in the dissemination of pathogenic E. coli in both water and sediments, even if the microbiological quality of the water was good or to average quality according to the French water index. PMID:28458656

In silico insights into protein-protein interactions and folding dynamics of the saposin-like domain of Solanum tuberosum aspartic protease.

PubMed

De Moura, Dref C; Bryksa, Brian C; Yada, Rickey Y

2014-01-01

The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum) plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L.) plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family.

In Silico Insights into Protein-Protein Interactions and Folding Dynamics of the Saposin-Like Domain of Solanum tuberosum Aspartic Protease

PubMed Central

De Moura, Dref C.; Bryksa, Brian C.; Yada, Rickey Y.

2014-01-01

The plant-specific insert is an approximately 100-residue domain found exclusively within the C-terminal lobe of some plant aspartic proteases. Structurally, this domain is a member of the saposin-like protein family, and is involved in plant pathogen defense as well as vacuolar targeting of the parent protease molecule. Similar to other members of the saposin-like protein family, most notably saposins A and C, the recently resolved crystal structure of potato (Solanum tuberosum) plant-specific insert has been shown to exist in a substrate-bound open conformation in which the plant-specific insert oligomerizes to form homodimers. In addition to the open structure, a closed conformation also exists having the classic saposin fold of the saposin-like protein family as observed in the crystal structure of barley (Hordeum vulgare L.) plant-specific insert. In the present study, the mechanisms of tertiary and quaternary conformation changes of potato plant-specific insert were investigated in silico as a function of pH. Umbrella sampling and determination of the free energy change of dissociation of the plant-specific insert homodimer revealed that increasing the pH of the system to near physiological levels reduced the free energy barrier to dissociation. Furthermore, principal component analysis was used to characterize conformational changes at both acidic and neutral pH. The results indicated that the plant-specific insert may adopt a tertiary structure similar to the characteristic saposin fold and suggest a potential new structural motif among saposin-like proteins. To our knowledge, this acidified PSI structure presents the first example of an alternative saposin-fold motif for any member of the large and diverse SAPLIP family. PMID:25188221

Genetic changes that accompanied shifts of low pathogenic avian influenza viruses toward higher pathogenicity in poultry

PubMed Central

Abdelwhab, El-Sayed M; Veits, Jutta; Mettenleiter, Thomas C

2013-01-01

Avian influenza viruses (AIV) of H5 and H7 subtypes exhibit two different pathotypes in poultry: infection with low pathogenic (LP) strains results in minimal, if any, health disturbances, whereas highly pathogenic (HP) strains cause severe morbidity and mortality. LPAIV of H5 and H7 subtypes can spontaneously mutate into HPAIV. Ten outbreaks caused by HPAIV are known to have been preceded by circulation of a predecessor LPAIV in poultry. Three of them were caused by H5N2 subtype and seven involved H7 subtype in combination with N1, N3, or N7. Here, we review those outbreaks and summarize the genetic changes which resulted in the transformation of LPAIV to HPAIV under natural conditions. Mutations that were found directly in those outbreaks are more likely to be linked to virulence, pathogenesis, and early adaptation of AIV. PMID:23863606

Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

NASA Astrophysics Data System (ADS)

Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip'Ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

2016-06-01

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

Bacterial community structure in experimental methanogenic bioreactors and search for pathogenic clostridia as community members.

PubMed

Dohrmann, Anja B; Baumert, Susann; Klingebiel, Lars; Weiland, Peter; Tebbe, Christoph C

2011-03-01

Microbial conversion of organic waste or harvested plant material into biogas has become an attractive technology for energy production. Biogas is produced in reactors under anaerobic conditions by a consortium of microorganisms which commonly include bacteria of the genus Clostridium. Since the genus Clostridium also harbors some highly pathogenic members in its phylogenetic cluster I, there has been some concern that an unintended growth of such pathogens might occur during the fermentation process. Therefore this study aimed to follow how process parameters affect the diversity of Bacteria in general, and the diversity of Clostridium cluster I members in particular. The development of both communities was followed in model biogas reactors from start-up during stable methanogenic conditions. The biogas reactors were run with either cattle or pig manures as substrates, and both were operated at mesophilic and thermophilic conditions. The structural diversity was analyzed independent of cultivation using a PCR-based detection of 16S rRNA genes and genetic profiling by single-strand conformation polymorphism (SSCP). Genetic profiles indicated that both bacterial and clostridial communities evolved in parallel, and the community structures were highly influenced by both substrate and temperature. Sequence analysis of 16S rRNA genes recovered from prominent bands from SSCP profiles representing Clostridia detected no pathogenic species. Thus, this study gave no indication that pathogenic clostridia would be enriched as dominant community members in biogas reactors fed with manure.

The coronafacoyl phytotoxins: structure, biosynthesis, regulation and biological activities.

PubMed

Bignell, Dawn R D; Cheng, Zhenlong; Bown, Luke

2018-05-01

Phytotoxins are secondary metabolites that contribute to the development and/or severity of diseases caused by various plant pathogenic microorganisms. The coronafacoyl phytotoxins are an important family of plant toxins that are known or suspected to be produced by several phylogenetically distinct plant pathogenic bacteria, including the gammaproteobacterium Pseudomonas syringae and the actinobacterium Streptomyces scabies. At least seven different family members have been identified, of which coronatine was the first to be described and is the best-characterized. Though nonessential for disease development, coronafacoyl phytotoxins appear to enhance the severity of disease symptoms induced by pathogenic microbes during host infection. In addition, the identification of coronafacoyl phytotoxin biosynthetic genes in organisms not known to be plant pathogens suggests that these metabolites may have additional roles other than as virulence factors. This review focuses on our current understanding of the structures, biosynthesis, regulation, biological activities and evolution of coronafacoyl phytotoxins as well as the different methods that are used to detect these metabolites and the organisms that produce them.

[Modern concepts of etiology, pathogenesis and treatment approaches to endo-perio lesions].

PubMed

Grudianov, A I; Makeeva, M K; Piatgorskaia, N V

2013-01-01

A combination ofperiodontitis and pulp or periapical tissues inflammation in one tooth is known as endo-periodontal lesions. Such kind of lesion is serious problem of modern dentistry. It was found that pathogenic microflora of periodontal pocket and root canal of tooth with eno-perio lesion is almost the equal and consist of anaerobic microorganisms. Pathogenic effects have not only microorganisms but also their life products. Apical foramen, lateral and additional canals are physiological ways for pathogens migration. Inflammatory processes in these structures complicate each other. Lack of information among dentists about treatment possibilities of endo-perio lesions is a main reasons of extraction such kind of teeth. Simultaneous elimination of pathogens both from periodontal pocket and root canal is a key factor for effective treatment. Periodontal status is main factor for prognosis of tooth with endo-perio lesion, because of it treatment of endo-perio lesions should consist of two stages: infection elimination and regeneration of tooth-supported structures.

Insights using the molecular model of Lipoxygenase from Finger millet (Eleusine coracana (L.)).

PubMed

Tiwari, Apoorv; Avashthi, Himanshu; Jha, Richa; Srivastava, Ambuj; Kumar Garg, Vijay; Wasudev Ramteke, Pramod; Kumar, Anil

2016-01-01

Lipoxygenase-1 (LOX-1) protein provides defense against pests and pathogens and its presence have been positively correlated with plant resistance against pathogens. Linoleate is a known substrate of lipoxygenase and it induces necrosis leading to the accumulation of isoflavonoid phytoalexins in plant leaves. Therefore, it is of interest to study the structural features of LOX-1 from Finger millet. However, the structure ofLOX-1 from Finger millet is not yet known. A homology model of LOX-1 from Finger millet is described. Domain architecture study suggested the presence of two domains namely PLAT (Phospho Lipid Acyl Transferase) and lipoxygenase. Molecular docking models of linoleate with lipoxygenase from finger millet, rice and sorghum are reported. The features of docked models showed that finger millet have higher pathogen resistance in comparison to other cereal crops. This data is useful for the molecular cloning of fulllength LOX-1 gene for validating its role in improving plant defense against pathogen infection and for various other biological processes.

Transmembrane transporter expression regulated by the glucosylceramide pathway in Cryptococcus neoformans.

PubMed

Singh, Arpita; Rella, Antonella; Schwacke, John; Vacchi-Suzzi, Caterina; Luberto, Chiara; Del Poeta, Maurizio

2015-11-16

The sphingolipid glucosylceramide (GlcCer) and factors involved in the fungal GlcCer pathways were shown earlier to be an integral part of fungal virulence, especially in fungal replication at 37 °C, in neutral/alkaline pH and 5 % CO2 environments (e.g. alveolar spaces). Two mutants, ∆gcs 1 lacking glucosylceramide synthase 1 gene (GCS1) which catalyzes the formation of sphingolipid GlcCer from the C9-methyl ceramide and ∆smt1 lacking sphingolipid C9 methyltransferase gene (SMT1), which adds a methyl group to position nine of the sphingosine backbone of ceramide, of this pathway were attenuated in virulence and have a growth defect at the above-mentioned conditions. These mutants with either no or structurally modified GlcCer located on the cell-membrane have reduced membrane rigidity, which may have altered not only the physical location of membrane proteins but also their expression, as the pathogen's mode of adaptation to changing need. Importantly, pathogens are known to adapt themselves to the changing host environments by altering their patterns of gene expression. By transcriptional analysis of gene expression, we identified six genes whose expression was changed from their wild-type counterpart grown in the same conditions, i.e. they became either down regulated or up regulated in these two mutants. The microarray data was validated by real-time PCR, which confirmed their fold change in gene expression. All the six genes we identified, viz siderochrome-iron transporter (CNAG_02083), monosaccharide transporter (CNAG_05340), glucose transporter (CNAG_03772), membrane protein (CNAG_03912), membrane transport protein (CNAG_00539), and sugar transporter (CNAG_06963), are membrane-localized and have significantly altered gene expression levels. Therefore, we hypothesize that these genes function either independently or in tandem with a structurally modified cell wall/plasma membrane resulting from the modifications of the GlcCer pathway and thus possibly disrupt transmembrane signaling complex, which in turn contributes to cryptococcal osmotic, pH, ion homeostasis and its pathobiology. Six genes identified from gene expression microarrays by gene set enrichment analysis and validated by RT-PCR, are membrane located and associated with the growth defect at neutral-alkaline pH due to the absence and or presence of a structurally modified GlcCer. They may be involved in the transmembrane signaling network in Cryptococcus neoformans, and therefore the pathobiology of the fungus in these conditions.

Pathogen transmission at stage-structured infectious patches: Killers and vaccinators.

PubMed

Caraco, Thomas; Turner, Wendy C

2018-01-07

Spatial localization of an obligate-killing, free-living pathogen generates a landscape of patches where new infections occur. As an infectious patch ages, both pathogen exposure at the patch and the probability of lethal infection following exposure can decline. We model stage-structured infectious patches, where non-lethal exposure can naturally "vaccinate" susceptible hosts. We let the between-stage difference in pathogen transmission, and then the between-stage difference in patch virulence, increase independently of other parameters. Effects of increasing either between-stage difference (about a fixed mean) depend on the probability a patch transitions from the first to second stage, i.e., the chance that a killer patch becomes a vaccinator. For slower stage transition, greater between-stage differences decreased susceptibles, and increased both resistant-host and killer patch numbers. But our examples reveal that each effect can be reversed when between-stage transition occurs more rapidly. For sufficiently rapid stage transition, increased between-stage virulence differences can lead to pathogen extinction, and leave the host at disease-free equilibrium. The model's general significance lies in demonstrating how epidemiological variation among sites of environmentally transmitted disease can strongly govern host-parasite dynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microbial Community Structures and Dynamics in the O3/BAC Drinking Water Treatment Process

PubMed Central

Tian, Jian; Lu, Jun; Zhang, Yu; Li, Jian-Cheng; Sun, Li-Chen; Hu, Zhang-Li

2014-01-01

Effectiveness of drinking water treatment, in particular pathogen control during the water treatment process, is always a major public health concern. In this investigation, the application of PCR-DGGE technology to the analysis of microbial community structures and dynamics in the drinking water treatment process revealed several dominant microbial populations including: α-Proteobacteria, β-Proteobacteria, γ-Proteobacteria, Bacteroidetes, Actinobacteria Firmicutes and Cyanobacteria. α-Proteobacteria and β-Proteobacteria were the dominant bacteria during the whole process. Bacteroidetes and Firmicutes were the dominant bacteria before and after treatment, respectively. Firmicutes showed season-dependent changes in population dynamics. Importantly, γ-Proteobacteria, which is a class of medically important bacteria, was well controlled by the O3/biological activated carbon (BAC) treatment, resulting in improved effluent water bio-safety. PMID:24937529

The structure of lactoferrin-binding protein B from Neisseria meningitidis suggests roles in iron acquisition and neutralization of host defences

PubMed Central

Brooks, Cory L.; Arutyunova, Elena; Lemieux, M. Joanne

2014-01-01

Pathogens have evolved a range of mechanisms to acquire iron from the host during infection. Several Gram-negative pathogens including members of the genera Neisseria and Moraxella have evolved two-component systems that can extract iron from the host glycoproteins lactoferrin and transferrin. The homologous iron-transport systems consist of a membrane-bound transporter and an accessory lipoprotein. While the mechanism behind iron acquisition from transferrin is well understood, relatively little is known regarding how iron is extracted from lactoferrin. Here, the crystal structure of the N-terminal domain (N-lobe) of the accessory lipoprotein lactoferrin-binding protein B (LbpB) from the pathogen Neisseria meningitidis is reported. The structure is highly homologous to the previously determined structures of the accessory lipoprotein transferrin-binding protein B (TbpB) and LbpB from the bovine pathogen Moraxella bovis. Docking the LbpB structure with lactoferrin reveals extensive binding interactions with the N1 subdomain of lactoferrin. The nature of the interaction precludes apolactoferrin from binding LbpB, ensuring the specificity of iron-loaded lactoferrin. The specificity of LbpB safeguards proper delivery of iron-bound lactoferrin to the transporter lactoferrin-binding protein A (LbpA). The structure also reveals a possible secondary role for LbpB in protecting the bacteria from host defences. Following proteolytic digestion of lactoferrin, a cationic peptide derived from the N-terminus is released. This peptide, called lactoferricin, exhibits potent antimicrobial effects. The docked model of LbpB with lactoferrin reveals that LbpB interacts extensively with the N-terminal lactoferricin region. This may provide a venue for preventing the production of the peptide by proteolysis, or directly sequestering the peptide, protecting the bacteria from the toxic effects of lactoferricin. PMID:25286931

Intrinsic disorder in pathogen effectors: protein flexibility as an evolutionary hallmark in a molecular arms race.

PubMed

Marín, Macarena; Uversky, Vladimir N; Ott, Thomas

2013-09-01

Effector proteins represent a refined mechanism of bacterial pathogens to overcome plants' innate immune systems. These modular proteins often manipulate host physiology by directly interfering with immune signaling of plant cells. Even if host cells have developed efficient strategies to perceive the presence of pathogenic microbes and to recognize intracellular effector activity, it remains an open question why only few effectors are recognized directly by plant resistance proteins. Based on in-silico genome-wide surveys and a reevaluation of published structural data, we estimated that bacterial effectors of phytopathogens are highly enriched in long-disordered regions (>50 residues). These structurally flexible segments have no secondary structure under physiological conditions but can fold in a stimulus-dependent manner (e.g., during protein-protein interactions). The high abundance of intrinsic disorder in effectors strongly suggests positive evolutionary selection of this structural feature and highlights the dynamic nature of these proteins. We postulate that such structural flexibility may be essential for (1) effector translocation, (2) evasion of the innate immune system, and (3) host function mimicry. The study of these dynamical regions will greatly complement current structural approaches to understand the molecular mechanisms of these proteins and may help in the prediction of new effectors.

A Conserved Surface Loop in Type I Dehydroquinate Dehydratases Positions an Active Site Arginine and Functions in Substrate Binding

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

Light, Samuel H.; Minasov, George; Shuvalova, Ludmilla

2012-04-18

Dehydroquinate dehydratase (DHQD) catalyzes the third step in the biosynthetic shikimate pathway. We present three crystal structures of the Salmonella enterica type I DHQD that address the functionality of a surface loop that is observed to close over the active site following substrate binding. Two wild-type structures with differing loop conformations and kinetic and structural studies of a mutant provide evidence of both direct and indirect mechanisms of involvement of the loop in substrate binding. In addition to allowing amino acid side chains to establish a direct interaction with the substrate, closure of the loop necessitates a conformational change ofmore » a key active site arginine, which in turn positions the substrate productively. The absence of DHQD in humans and its essentiality in many pathogenic bacteria make the enzyme a target for the development of nontoxic antimicrobials. The structures and ligand binding insights presented here may inform the design of novel type I DHQD inhibiting molecules.« less

Changes in adaptation of H5N2 highly pathogenic avian influenza H5 clade 2.3.4.4 viruses in chickens and mallards

USDA-ARS?s Scientific Manuscript database

H5N2 highly pathogenic avian influenza (HPAI) viruses caused a severe poultry outbreak in the United States (U.S.) during 2015. In order to examine changes in adaptation of this viral lineage, the infectivity, transmission and pathogenesis of poultry H5N2 viruses was investigated in chickens and mal...

New perspectives on evolutionary medicine: the relevance of microevolution for human health and disease

PubMed Central

2013-01-01

Evolutionary medicine (EM) is a growing field focusing on the evolutionary basis of human diseases and their changes through time. To date, the majority of EM studies have used pure theories of hominin macroevolution to explain the present-day state of human health. Here, we propose a different approach by addressing more empirical and health-oriented research concerning past, current and future microevolutionary changes of human structure, functions and pathologies. Studying generation-to-generation changes of human morphology that occurred in historical times, and still occur in present-day populations under the forces of evolution, helps to explain medical conditions and warns clinicians that their current practices may influence future humans. Also, analyzing historic tissue specimens such as mummies is crucial in order to address the molecular evolution of pathogens, of the human genome, and their coadaptations. PMID:23627943

Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

PubMed

Grissett, G P; White, B J; Larson, R L

2015-01-01

Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Population genomics of Fusarium graminearum reveals signatures of divergent evolution within a major cereal pathogen

PubMed Central

2018-01-01

The cereal pathogen Fusarium graminearum is the primary cause of Fusarium head blight (FHB) and a significant threat to food safety and crop production. To elucidate population structure and identify genomic targets of selection within major FHB pathogen populations in North America we sequenced the genomes of 60 diverse F. graminearum isolates. We also assembled the first pan-genome for F. graminearum to clarify population-level differences in gene content potentially contributing to pathogen diversity. Bayesian and phylogenomic analyses revealed genetic structure associated with isolates that produce the novel NX-2 mycotoxin, suggesting a North American population that has remained genetically distinct from other endemic and introduced cereal-infecting populations. Genome scans uncovered distinct signatures of selection within populations, focused in high diversity, frequently recombining regions. These patterns suggested selection for genomic divergence at the trichothecene toxin gene cluster and thirteen additional regions containing genes potentially involved in pathogen specialization. Gene content differences further distinguished populations, in that 121 genes showed population-specific patterns of conservation. Genes that differentiated populations had predicted functions related to pathogenesis, secondary metabolism and antagonistic interactions, though a subset had unique roles in temperature and light sensitivity. Our results indicated that F. graminearum populations are distinguished by dozens of genes with signatures of selection and an array of dispensable accessory genes, suggesting that FHB pathogen populations may be equipped with different traits to exploit the agroecosystem. These findings provide insights into the evolutionary processes and genomic features contributing to population divergence in plant pathogens, and highlight candidate genes for future functional studies of pathogen specialization across evolutionarily and ecologically diverse fungi. PMID:29584736

Evaluation and Comparison of the Pathogenicity and Host Immune Responses Induced by a G2b Taiwan Porcine Epidemic Diarrhea Virus (Strain Pintung 52) and Its Highly Cell-Culture Passaged Strain in Conventional 5-Week-Old Pigs.

PubMed

Chang, Yen-Chen; Kao, Chi-Fei; Chang, Chia-Yu; Jeng, Chian-Ren; Tsai, Pei-Shiue; Pang, Victor Fei; Chiou, Hue-Ying; Peng, Ju-Yi; Cheng, Ivan-Chen; Chang, Hui-Wen

2017-05-19

A genogroup 2b (G2b) porcine epidemic diarrhea virus (PEDV) Taiwan Pintung 52 (PEDVPT) strain was isolated in 2014. The pathogenicity and host antibody responses elicited by low-passage (passage 5; PEDVPT-P5) and high-passage (passage 96; PEDVPT-P96) PEDVPT strains were compared in post-weaning PEDV-seronegative pigs by oral inoculation. PEDVPT-P5-inoculation induced typical diarrhea during 1-9 days post inoculation with fecal viral shedding persisting for 26 days. Compared to PEDVPT-P5, PEDVPT-P96 inoculation induced none-to-mild diarrhea and lower, delayed fecal viral shedding. Although PEDVPT-P96 elicited slightly lower neutralizing antibodies and PEDV-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) titers, a reduction in pathogenicity and viral shedding of the subsequent challenge with PEDVPT-P5 were noted in both PEDVPT-P5- and PEDVPT-P96-inoculated pigs. Alignment and comparison of full-length sequences of PEDVPT-P5 and PEDVPT-P96 revealed 23 nucleotide changes and resultant 19 amino acid substitutions in non-structure proteins 2, 3, 4, 9, 14, 15, spike, open reading frame 3 (ORF3), and membrane proteins with no detectable deletion or insertion. The present study confirmed the pathogenicity of the PEDVPT isolate in conventional post-weaning pigs. Moreover, data regarding viral attenuation and potency of induced antibodies against PEDVPT-P5 identified PEDVPT-P96 as a potential live-attenuated vaccine candidate.

Linking evolutionary lineage with parasite and pathogen prevalence in the Iberian honey bee.

PubMed

Jara, Laura; Cepero, Almudena; Garrido-Bailón, Encarna; Martín-Hernández, Raquel; Higes, Mariano; De la Rúa, Pilar

2012-05-01

The recent decline in honey bee colonies observed in both European countries and worldwide is of great interest and concern, although the underlying causes remain poorly understood. In recent years, growing evidence has implicated parasites and pathogens in this decline of both the vitality and number of honey bee colonies. The Iberian Peninsula provides an interesting environment in which to study the occurrence of pathogens and parasites in the host honey bee populations due to the presence of two evolutionary lineages in A. m. iberiensis (Western European [M] or African [A]). Here, we provide the first evidence linking the population structure of the Iberian honey bee with the prevalence of some of its most important parasites and pathogens: the Varroa destructor mite and the microsporidia Nosema apis and Nosema ceranae. Using data collected in two surveys conducted in 2006 and 2010 in 41 Spanish provinces, the evolutionary lineage and the presence of the three parasitic organisms cited above were analyzed in a total of 228 colonies. In 2006 N. apis was found in a significantly higher proportion of M lineage honey bees than in the A lineage. However, in 2010 this situation had changed significantly due to a higher prevalence of N. ceranae. We observed no significant relationships in either year between the distributions of V. destructor or N. ceranae and the evolutionary lineage present in A. m. iberiensis colonies, but the effects of these organisms on the genetic diversity of the honey bee populations need further research. Copyright © 2012 Elsevier Inc. All rights reserved.

Activation of an AP1-Like Transcription Factor of the Maize Pathogen Cochliobolus heterostrophus in Response to Oxidative Stress and Plant Signals

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

Lev, Sophie; hadar, Ruthi; Amedeo, Paolo

Redox sensing is a ubiquitous mechanism regulating cellular activity. Fungal pathogens face reactive oxygen species produced by the host plant's oxidative burst in addition to endogenous reactive oxygen species produced during aerobic metabolism. An array of preformed and induced detoxifying enzymes, including superoxide dismutase, catalases, and peroxidases, could allow fungi to infect plants despite the oxidative burst. We isolated a gene (CHAP1) encoding a redox-regulated transcription factor in Cochliobolus heterostrophus, a fungal pathogen of maize. CHAP1 is a bZIP protein that possesses two cysteine-rich domains structurally and functionally related to Saccharomyces cerevisiae YAP1. Deletion of CHAP1 in C. heterostrophus resultedmore » in decreased resistance to oxidative stress caused by hydrogen peroxide and menadione, but the virulence of chap1 mutants was unaffected. Upon activation by oxidizing agents or plant signals, a green fluorescent protein (GFP)-CHAP1 fusion protein became localized in the nucleus. Expression of genes encoding antioxidant proteins was induced in the wild type but not in chap1 mutants. Activation of CHAP1 occurred from the earliest stage of plant infection, in conidial germ tubes on the leaf surface, and persisted during infection. Late in the course of infection, after extensive necrotic lesions were formed, GFP-CHAP1 redistributed to the cytosol in hyphae growing on the leaf surface. Localization of CHAP1 to the nucleus may, through changes in the redox state of the cell, provide a mechanism linking extracellular cues to transcriptional regulation during the plant-pathogen interaction.« less

Real-world clinical applicability of pathogenicity predictors assessed on SERPINA1 mutations in alpha-1-antitrypsin deficiency.

PubMed

Giacopuzzi, Edoardo; Laffranchi, Mattia; Berardelli, Romina; Ravasio, Viola; Ferrarotti, Ilaria; Gooptu, Bibek; Borsani, Giuseppe; Fra, Annamaria

2018-06-07

The growth of publicly available data informing upon genetic variations, mechanisms of disease and disease sub-phenotypes offers great potential for personalised medicine. Computational approaches are likely required to assess large numbers of novel genetic variants. However, the integration of genetic, structural and pathophysiological data still represents a challenge for computational predictions and their clinical use. We addressed these issues for alpha-1-antitrypsin deficiency, a disease mediated by mutations in the SERPINA1 gene encoding alpha-1-antitrypsin. We compiled a comprehensive database of SERPINA1 coding mutations and assigned them apparent pathological relevance based upon available data. 'Benign' and 'Pathogenic' mutations were used to assess performance of 31 pathogenicity predictors. Well-performing algorithms clustered the subset of variants known to be severely pathogenic with high scores. Eight new mutations identified in the ExAC database and achieving high scores were selected for characterisation in cell models and showed secretory deficiency and polymer formation, supporting the predictive power of our computational approach. The behaviour of the pathogenic new variants and consistent outliers were rationalised by considering the protein structural context and residue conservation. These findings highlight the potential of computational methods to provide meaningful predictions of the pathogenic significance of novel mutations and identify areas for further investigation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Can Horton hear the whos? The importance of scale in mosquito-borne disease.

PubMed

Lord, C C; Alto, B W; Anderson, S L; Connelly, C R; Day, J F; Richards, S L; Smartt, C T; Tabachnick, W J

2014-03-01

The epidemiology of vector-borne pathogens is determined by mechanisms and interactions at different scales of biological organization, from individual-level cellular processes to community interactions between species and with the environment. Most research, however, focuses on one scale or level with little integration between scales or levels within scales. Understanding the interactions between levels and how they influence our perception of vector-borne pathogens is critical. Here two examples of biological scales (pathogen transmission and mosquito mortality) are presented to illustrate some of the issues of scale and to explore how processes on different levels may interact to influence mosquito-borne pathogen transmission cycles. Individual variation in survival, vector competence, and other traits affect population abundance, transmission potential, and community structure. Community structure affects interactions between individuals such as competition and predation, and thus influences the individual-level dynamics and transmission potential. Modeling is a valuable tool to assess interactions between scales and how processes at different levels can affect transmission dynamics. We expand an existing model to illustrate the types of studies needed, showing that individual-level variation in viral dose acquired or needed for infection can influence the number of infectious vectors. It is critical that interactions within and among biological scales and levels of biological organization are understood for greater understanding of pathogen transmission with the ultimate goal of improving control of vector-borne pathogens.

[Change of host's behavior including man under the influence of parasites].

PubMed

Sergiev, V P

2010-01-01

Directed modulation of hosts' behavior favouring transmission of pathogen was noted in many parasites and, above all, in helminthes, which life cycle includes the consequent change of several hosts. It turned out that parasites use the same neuromediators for change of behavior of both mammals and hosts belonging to other animal classes. In fishes as well as in mammals, monoamines-neurotransmitters assist in brain functioning. Norepinephrine, dopamine and serotonin affect the alimentation, motion activity, aggression and social behaviour. Changes in concentration ratio of serotonin and its metabolites in invaded species were more pronounced, which pointed to directed effects of pathogens on serotonin activity. The same effect of some pathogens on human behaviour does not have selective significance because humans are not an essential link in life cycle of many parasites. Although the mentioned effect on behaviour could lead to negative consequences. For examples, persons with latent toxoplasmosis are significantly more frequent become members or victims of traffic accidents due to decreased ability for concentration of attention.

Solution NMR studies provide structural basis for endotoxin pattern recognition by the innate immune receptor CD14

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

Albright, Seth; Chen Bin; Holbrook, Kristen

CD14 functions as a key pattern recognition receptor for a diverse array of Gram-negative and Gram-positive cell-wall components in the host innate immune response by binding to pathogen-associated molecular patterns (PAMPs) at partially overlapping binding site(s). To determine the potential contribution of CD14 residues in this pattern recognition, we have examined using solution NMR spectroscopy, the binding of three different endotoxin ligands, lipopolysaccharide, lipoteichoic acid, and a PGN-derived compound, muramyl dipeptide to a {sup 15}N isotopically labeled 152-residue N-terminal fragment of sCD14 expressed in Pichia pastoris. Mapping of NMR spectral changes upon addition of ligands revealed that the pattern ofmore » residues affected by binding of each ligand is partially similar and partially different. This first direct structural observation of the ability of specific residue combinations of CD14 to differentially affect endotoxin binding may help explain the broad specificity of CD14 in ligand recognition and provide a structural basis for pattern recognition. Another interesting finding from the observed spectral changes is that the mode of binding may be dynamically modulated and could provide a mechanism for binding endotoxins with structural diversity through a common binding site.« less

The evolution of plant secretory structures and emergence of terpenoid chemical diversity.

PubMed

Lange, Bernd Markus

2015-01-01

Secretory structures in terrestrial plants appear to have first emerged as intracellular oil bodies in liverworts. In vascular plants, internal secretory structures, such as resin ducts and laticifers, are usually found in conjunction with vascular bundles, whereas subepidermal secretory cavities and epidermal glandular trichomes generally have more complex tissue distribution patterns. The primary function of plant secretory structures is related to defense responses, both constitutive and induced, against herbivores and pathogens. The ability to sequester secondary (or specialized) metabolites and defense proteins in secretory structures was a critical adaptation that shaped plant-herbivore and plant-pathogen interactions. Although this review places particular emphasis on describing the evolution of pathways leading to terpenoids, it also assesses the emergence of other metabolite classes to outline the metabolic capabilities of different plant lineages.

Raman spectroscopy for the microbiological characterization and identification of medically relevant bacteria

NASA Astrophysics Data System (ADS)

Hamasha, Khozima Mahmoud

The detection and identification of pathogenic bacteria has become more important than ever due to the increase of potential bioterrorism threats and the high mortality rate of bacterial infections worldwide. Raman spectroscopy has recently gained popularity as an attractive robust approach for the molecular characterization, rapid identification, and accurate classification of a wide range of bacteria. In this dissertation, Raman spectroscopy utilizing advanced statistical techniques was used to identify and discriminate between different pathogenic and non-pathogenic bacterial strains of E. coli and Staphylococcus aureus bacterial species by probing the molecular compositions of the cells. The five-carbon sugar xylitol, which cannot be metabolized by the oral and nasopharyngeal bacteria, had been recognized by clinicians as a preventive agents for dental caries and many studies have demonstrated that xylitol causes a reduction in otitis media (chronic inner ear infections) and other nasopharyngeal infections. Raman spectroscopy was used to characterize the uptake and metabolic activity of xylitol in pathogenic (viridans group Streptococcus) and nonpathogenic (E. coli) bacteria by taking their Raman spectra before xylitol exposure and after growing with xylitol and quantifying the significant differences in the molecular vibrational modes due to this exposure. The results of this study showed significant stable spectral changes in the S. viridians bacteria induced by xylitol and those changes were not the same as in some E. coli strains. Finally, Raman spectroscopy experiments were conducted to provide important information about the function of a certain protein (wag31) of Mycobacterium tuberculosis using a relative non-pathogenic bacterium called Mycobacterium smegmatis. Raman spectra of conditional mutants of bacteria expressing three different phosphorylation forms of wag31 were collected and analyzed. The results show that that the phosphorylation of wag31 causes significant differences in the molecular structure, namely the quantity of amino acids associated with peptidoglycan precursor proteins and lipid II as observed in the Raman spectra of these cells. Raman spectra were also acquired from the isolated cell envelope fraction of the cells expressing different forms of wag31 and the results showed that a significant number of the molecular vibrational differences observed in the cells were also observed in the cell envelope fraction, indicating that these differences are localized in the cell envelope.

Pathogenic variation of Phakopsora pachyrhizi infecting soybean in Nigeria

USDA-ARS?s Scientific Manuscript database

Soybean rust, caused by Phakopsora pachyrhizi, is a major disease in many soybean-producing areas in Nigeria. To determine the virulence and the genetic structure of Nigerian field populations of the soybean rust pathogen, a total of 116 purified isolates established from infected leaves randomly co...

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

Interaction effects of different drivers of wild bee decline and their influence on host-pathogen dynamics.

PubMed

Meeus, Ivan; Pisman, Matti; Smagghe, Guy; Piot, Niels

2018-04-01

Wild bee decline is a multi-factorial problem, yet it is crucial to understand the impact of a single driver. Hereto the interaction effects of wild bee decline with multiple natural and anthropogenic stressors need to be clear. This is also true for the driver 'pathogens', as stressor induced disturbances of natural host-pathogen dynamics can unbalance settled virulence equilibria. Invasive species, bee domestication, habitat loss, climate changes and insecticides are recognized drivers of wild bee decline, but all influence host-pathogen dynamics as well. Many wild bee pathogens have multiple hosts, which relaxes the host-density limitation of virulence evolution. In conclusion, disturbances of bee-pathogen dynamics can be compared to a game of Russian roulette. Copyright © 2018. Published by Elsevier Inc.

Genetic structure and demographic history of Colletotrichum gloeosporioides sensu lato and C. truncatum isolates from Trinidad and Mexico.

PubMed

Rampersad, Sephra N; Perez-Brito, Daisy; Torres-Calzada, Claudia; Tapia-Tussell, Raul; Carrington, Christine V F

2013-06-22

C. gloeosporioides sensu lato is one of the most economically important post-harvest diseases affecting papaya production worldwide. There is currently no information concerning the genetic structure or demographic history of this pathogen in any of the affected countries. Knowledge of molecular demographic parameters for different populations will improve our understanding of the biogeographic history as well as the evolutionary and adaptive potential of these pathogens. In this study, sequence data for ACT, GPDH, β-TUB and ITS gene regions were analyzed for C. gloeosporioides sensu lato and C. truncatum isolates infecting papaya in Trinidad and Mexico in order to determine the genetic structure and demographic history of these populations. The data indicated that Mexico is the ancestral C. gloeosporioides sensu lato population with asymmetrical migration to Trinidad. Mexico also had the larger effective population size but, both Mexico and Trinidad populations exhibited population expansion. Mexico also had greater nucleotide diversity and high levels of diversity for each gene. There was significant sub-division of the Trinidad and Mexico populations and low levels of genetic divergence among populations for three of the four gene regions; β-TUB was shown to be under positive selection. There were also dissimilar haplotype characteristics for both populations. Mutation may play a role in shaping the population structure of C. gloeosporioides sensu lato isolates from Trinidad and from Mexico, especially with respect to the ACT and GPDH gene regions. There was no evidence of gene flow between the C. truncatum populations and it is possible that the Mexico and Trinidad populations emerged independently of each other. The study revealed relevant information based on the genetic structure as well as the demographic history of two fungal pathogens infecting papaya, C. gloeosporioides sensu lato and C. truncatum, in Trinidad and Mexico. Understanding the genetic structure of pathogen populations will assist in determining the evolutionary potential of the pathogen and in identifying which evolutionary forces may have the greatest impact on durability of resistance. Intervention strategies that target these evolutionary forces would prove to be the most practical.

Genetic structure and demographic history of Colletotrichum gloeosporioides sensu lato and C. truncatum isolates from Trinidad and Mexico

PubMed Central

2013-01-01

Background C. gloeosporioides sensu lato is one of the most economically important post-harvest diseases affecting papaya production worldwide. There is currently no information concerning the genetic structure or demographic history of this pathogen in any of the affected countries. Knowledge of molecular demographic parameters for different populations will improve our understanding of the biogeographic history as well as the evolutionary and adaptive potential of these pathogens. In this study, sequence data for ACT, GPDH, β-TUB and ITS gene regions were analyzed for C. gloeosporioides sensu lato and C. truncatum isolates infecting papaya in Trinidad and Mexico in order to determine the genetic structure and demographic history of these populations. Results The data indicated that Mexico is the ancestral C. gloeosporioides sensu lato population with asymmetrical migration to Trinidad. Mexico also had the larger effective population size but, both Mexico and Trinidad populations exhibited population expansion. Mexico also had greater nucleotide diversity and high levels of diversity for each gene. There was significant sub-division of the Trinidad and Mexico populations and low levels of genetic divergence among populations for three of the four gene regions; β-TUB was shown to be under positive selection. There were also dissimilar haplotype characteristics for both populations. Mutation may play a role in shaping the population structure of C. gloeosporioides sensu lato isolates from Trinidad and from Mexico, especially with respect to the ACT and GPDH gene regions. There was no evidence of gene flow between the C. truncatum populations and it is possible that the Mexico and Trinidad populations emerged independently of each other. Conclusions The study revealed relevant information based on the genetic structure as well as the demographic history of two fungal pathogens infecting papaya, C. gloeosporioides sensu lato and C. truncatum, in Trinidad and Mexico. Understanding the genetic structure of pathogen populations will assist in determining the evolutionary potential of the pathogen and in identifying which evolutionary forces may have the greatest impact on durability of resistance. Intervention strategies that target these evolutionary forces would prove to be the most practical. PMID:23800297

Epigenetic Mechanisms: An Emerging Player in Plant-Microbe Interactions.

PubMed

Zhu, Qian-Hao; Shan, Wei-Xing; Ayliffe, Michael A; Wang, Ming-Bo

2016-03-01

Plants have developed diverse molecular and cellular mechanisms to cope with a lifetime of exposure to a variety of pathogens. Host transcriptional reprogramming is a central part of plant defense upon pathogen recognition. Recent studies link DNA methylation and demethylation as well as chromatin remodeling by posttranslational histone modifications, including acetylation, methylation, and ubiquitination, to changes in the expression levels of defense genes upon pathogen challenge. Remarkably these inducible defense mechanisms can be primed prior to pathogen attack by epigenetic modifications and this heightened resistance state can be transmitted to subsequent generations by inheritance of these modification patterns. Beside the plant host, epigenetic mechanisms have also been implicated in virulence development of pathogens. This review highlights recent findings and insights into epigenetic mechanisms associated with interactions between plants and pathogens, in particular bacterial and fungal pathogens, and demonstrates the positive role they can have in promoting plant defense.

History of Mosquitoborne Diseases in the United States and Implications for New Pathogens.

PubMed

Moreno-Madriñán, Max J; Turell, Michael

2018-05-01

The introduction and spread of West Nile virus and the recent introduction of chikungunya and Zika viruses into the Americas have raised concern about the potential for various tropical pathogens to become established in North America. A historical analysis of yellow fever and malaria incidences in the United States suggests that it is not merely a temperate climate that keeps these pathogens from becoming established. Instead, socioeconomic changes are the most likely explanation for why these pathogens essentially disappeared from the United States yet remain a problem in tropical areas. In contrast to these anthroponotic pathogens that require humans in their transmission cycle, zoonotic pathogens are only slightly affected by socioeconomic factors, which is why West Nile virus became established in North America. In light of increasing globalization, we need to be concerned about the introduction of pathogens such as Rift Valley fever, Japanese encephalitis, and Venezuelan equine encephalitis viruses.

Pathogenic Gene Screening of Mycobacterium tuberculosis by Literature Data Mining and Information Pathway Enrichment Analysis.

PubMed

Xu, Guangyu; Wen, Simin; Pan, Yuchen; Zhang, Nan; Wang, Yuanyi

2018-05-01

Recent studies have unraveled mutations which have led to changes in the original conformation of functional proteins targeted by frontline drugs against Mycobacterium tuberculosis. These mutations are likely responsible for the emergence of drug-resistant strains of M. tuberculosis. Identification of new therapeutic targets is fundamental to the development of novel anti-TB drugs. Boost evolution analysis of interactome data with use of high-throughput biological experimental technologies provides opportunities for identification of pathogenic genes and for screening out novel therapeutic targets. In this study, we identified 584 proven pathogenic genes of M. tuberculosis and new pathogenic genes via bibliometrics and relevant websites such as PubMed, KEGG, and DOOR websites. We identified 13 new genes that are most likely to be pathogenic. This study may contribute to the discovery of new pathogenic genes and help unravel new functions of known pathogenic genes of M. tuberculosis.

Nitric Oxide in the Offensive Strategy of Fungal and Oomycete Plant Pathogens

PubMed Central

Arasimowicz-Jelonek, Magdalena; Floryszak-Wieczorek, Jolanta

2016-01-01

In the course of evolutionary changes pathogens have developed many invasion strategies, to which the host organisms responded with a broad range of defense reactions involving endogenous signaling molecules, such as nitric oxide (NO). There is evidence that pathogenic microorganisms, including two most important groups of eukaryotic plant pathogens, also acquired the ability to synthesize NO via non-unequivocally defined oxidative and/or reductive routes. Although the both kingdoms Chromista and Fungi are remarkably diverse, the experimental data clearly indicate that pathogen-derived NO is an important regulatory molecule controlling not only developmental processes, but also pathogen virulence and its survival in the host. An active control of mitigation or aggravation of nitrosative stress within host cells seems to be a key determinant for the successful invasion of plant pathogens representing different lifestyles and an effective mode of dispersion in various environmental niches. PMID:26973690

Maize-Pathogen Interactions: An Ongoing Combat from a Proteomics Perspective.

PubMed

Pechanova, Olga; Pechan, Tibor

2015-11-30

Maize (Zea mays L.) is a host to numerous pathogenic species that impose serious diseases to its ear and foliage, negatively affecting the yield and the quality of the maize crop. A considerable amount of research has been carried out to elucidate mechanisms of maize-pathogen interactions with a major goal to identify defense-associated proteins. In this review, we summarize interactions of maize with its agriculturally important pathogens that were assessed at the proteome level. Employing differential analyses, such as the comparison of pathogen-resistant and susceptible maize varieties, as well as changes in maize proteomes after pathogen challenge, numerous proteins were identified as possible candidates in maize resistance. We describe findings of various research groups that used mainly mass spectrometry-based, high through-put proteomic tools to investigate maize interactions with fungal pathogens Aspergillus flavus, Fusarium spp., and Curvularia lunata, and viral agents Rice Black-streaked Dwarf Virus and Sugarcane Mosaic Virus.

Maize-Pathogen Interactions: An Ongoing Combat from a Proteomics Perspective

PubMed Central

Pechanova, Olga; Pechan, Tibor

2015-01-01

Maize (Zea mays L.) is a host to numerous pathogenic species that impose serious diseases to its ear and foliage, negatively affecting the yield and the quality of the maize crop. A considerable amount of research has been carried out to elucidate mechanisms of maize-pathogen interactions with a major goal to identify defense-associated proteins. In this review, we summarize interactions of maize with its agriculturally important pathogens that were assessed at the proteome level. Employing differential analyses, such as the comparison of pathogen-resistant and susceptible maize varieties, as well as changes in maize proteomes after pathogen challenge, numerous proteins were identified as possible candidates in maize resistance. We describe findings of various research groups that used mainly mass spectrometry-based, high through-put proteomic tools to investigate maize interactions with fungal pathogens Aspergillus flavus, Fusarium spp., and Curvularia lunata, and viral agents Rice Black-streaked Dwarf Virus and Sugarcane Mosaic Virus. PMID:26633370

Evolutionary genomics of yeast pathogens in the Saccharomycotina

PubMed Central

Naranjo-Ortíz, Miguel A.; Marcet-Houben, Marina

2016-01-01

Saccharomycotina comprises a diverse group of yeasts that includes numerous species of industrial or clinical relevance. Opportunistic pathogens within this clade are often assigned to the genus Candida but belong to phylogenetically distant lineages that also comprise non-pathogenic species. This indicates that the ability to infect humans has evolved independently several times among Saccharomycotina. Although the mechanisms of infection of the main groups of Candida pathogens are starting to be unveiled, we still lack sufficient understanding of the evolutionary paths that led to a virulent phenotype in each of the pathogenic lineages. Deciphering what genomic changes underlie the evolutionary emergence of a virulence trait will not only aid the discovery of novel virulence mechanisms but it will also provide valuable information to understand how new pathogens emerge, and what clades may pose a future danger. Here we review recent comparative genomics efforts that have revealed possible evolutionary paths to pathogenesis in different lineages, focusing on the main three agents of candidiasis worldwide: Candida albicans, C. parapsilosis and C. glabrata. We will discuss what genomic traits may facilitate the emergence of virulence, and focus on two different genome evolution mechanisms able to generate drastic phenotypic changes and which have been associated to the emergence of virulence: gene family expansion and interspecies hybridization. PMID:27493146

The plant nitrogen mobilization promoted by Colletotrichum lindemuthianum in Phaseolus leaves depends on fungus pathogenicity.

PubMed

Tavernier, Virginie; Cadiou, Sandrine; Pageau, Karine; Laugé, Richard; Reisdorf-Cren, Michèle; Langin, Thierry; Masclaux-Daubresse, Céline

2007-01-01

Nitrogen plays an essential role in the nutrient relationship between plants and pathogens. Some studies report that the nitrogen-mobilizing plant metabolism that occurs during abiotic and biotic stress could be a 'slash-and-burn' defence strategy. In order to study nitrogen recycling and mobilization in host plants during pathogen attack and invasion, the Colletotrichum lindemuthianum/Phaseolus vulgaris interaction was used as a model. C. lindemuthianum is a hemibiotroph that causes anthracnose disease on P. vulgaris. Non-pathogenic mutants and the pathogenic wild-type strain were used to compare their effects on plant metabolism. The deleterious effects of infection were monitored by measuring changes in chlorophyll, protein, and amino acid concentrations. It was shown that amino acid composition changed depending on the plant-fungus interaction and that glutamine accumulated mainly in the leaves infected by the pathogenic strain. Glutamine accumulation correlated with the accumulation of cytosolic glutamine synthetase (GS1 alpha) mRNA. The most striking result was that the GS1 alpha gene was induced in all the fungus-infected leaves, independent of the strain used for inoculation, and that GS1 alpha expression paralleled the PAL3 and CHS defence gene expression. It is concluded that a role of GS1 alpha in plant defence has to be considered.

Coastal development and precipitation drive pathogen flow from land to sea: evidence from a Toxoplasma gondii and felid host system

PubMed Central

VanWormer, Elizabeth; Carpenter, Tim E; Singh, Purnendu; Shapiro, Karen; Wallender, Wesley W.; Conrad, Patricia A.; Largier, John L.; Maneta, Marco P.; Mazet, Jonna A. K.

2016-01-01

Rapidly developing coastal regions face consequences of land use and climate change including flooding and increased sediment, nutrient, and chemical runoff, but these forces may also enhance pathogen runoff, which threatens human, animal, and ecosystem health. Using the zoonotic parasite Toxoplasma gondii in California, USA as a model for coastal pathogen pollution, we examine the spatial distribution of parasite runoff and the impacts of precipitation and development on projected pathogen delivery to the ocean. Oocysts, the extremely hardy free-living environmental stage of T. gondii shed in faeces of domestic and wild felids, are carried to the ocean by freshwater runoff. Linking spatial pathogen loading and transport models, we show that watersheds with the highest levels of oocyst runoff align closely with regions of increased sentinel marine mammal T. gondii infection. These watersheds are characterized by higher levels of coastal development and larger domestic cat populations. Increases in coastal development and precipitation independently raised oocyst delivery to the ocean (average increases of 44% and 79%, respectively), but dramatically increased parasite runoff when combined (175% average increase). Anthropogenic changes in landscapes and climate can accelerate runoff of diverse pathogens from terrestrial to aquatic environments, influencing transmission to people, domestic animals, and wildlife. PMID:27456911

A high-sensitivity optical device for the early monitoring of plant pathogen attack via the in vivo detection of ROS bursts

PubMed Central

Zeng, Lizhang; Zhou, Jun; Li, Bo; Xing, Da

2015-01-01

Biotic stressors, especially pathogenic microorganisms, are rather difficult to detect. In plants, one of the earliest cellular responses following pathogen infection is the production of reactive oxygen species (ROS). In this study, a novel optical device for the early monitoring of Pseudomonas attack was developed; this device measures the ROS level via oxidation-sensitive 2′, 7′-dichlorodihydrofluorescein diacetate (H2DCFDA)-mediated fluorescence, which could provide early monitoring of attacks by a range of plant pathogen; ROS bursts were detected in vivo in Arabidopsis thaliana with higher sensitivity and accuracy than those of a commercial luminescence spectrophotometer. Additionally, the DCF fluorescence truly reflected early changes in the ROS level, as indicated by an evaluation of the H2O2 content and the tight association between the ROS and Pseudomonas concentration. Moreover, compared with traditional methods for detecting plant pathogen attacks based on physiological and biochemical measurements, our proposed technique also offers significant advantages, such as low cost, simplicity, convenient operation and quick turnaround. These results therefore suggest that the proposed optical device could be useful for the rapid monitoring of attacks by plant pathogen and yield results considerably earlier than the appearance of visual changes in plant morphology or growth. PMID:25767474

Coastal development and precipitation drive pathogen flow from land to sea: evidence from a Toxoplasma gondii and felid host system.

PubMed

VanWormer, Elizabeth; Carpenter, Tim E; Singh, Purnendu; Shapiro, Karen; Wallender, Wesley W; Conrad, Patricia A; Largier, John L; Maneta, Marco P; Mazet, Jonna A K

2016-07-26

Rapidly developing coastal regions face consequences of land use and climate change including flooding and increased sediment, nutrient, and chemical runoff, but these forces may also enhance pathogen runoff, which threatens human, animal, and ecosystem health. Using the zoonotic parasite Toxoplasma gondii in California, USA as a model for coastal pathogen pollution, we examine the spatial distribution of parasite runoff and the impacts of precipitation and development on projected pathogen delivery to the ocean. Oocysts, the extremely hardy free-living environmental stage of T. gondii shed in faeces of domestic and wild felids, are carried to the ocean by freshwater runoff. Linking spatial pathogen loading and transport models, we show that watersheds with the highest levels of oocyst runoff align closely with regions of increased sentinel marine mammal T. gondii infection. These watersheds are characterized by higher levels of coastal development and larger domestic cat populations. Increases in coastal development and precipitation independently raised oocyst delivery to the ocean (average increases of 44% and 79%, respectively), but dramatically increased parasite runoff when combined (175% average increase). Anthropogenic changes in landscapes and climate can accelerate runoff of diverse pathogens from terrestrial to aquatic environments, influencing transmission to people, domestic animals, and wildlife.

Interactions between the microbiota and pathogenic bacteria in the gut

PubMed Central

Bäumler, Andreas J.; Sperandio, Vanessa

2016-01-01

The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases. PMID:27383983

Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions

PubMed Central

Cheong, Chang Heon; Lee, Seonhye

2018-01-01

The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system’s inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens. PMID:29534043

Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions.

PubMed

Cheong, Chang Heon; Lee, Seonhye

2018-03-13

The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system's inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens.

Interactions between the microbiota and pathogenic bacteria in the gut.

PubMed

Bäumler, Andreas J; Sperandio, Vanessa

2016-07-07

The microbiome has an important role in human health. Changes in the microbiota can confer resistance to or promote infection by pathogenic bacteria. Antibiotics have a profound impact on the microbiota that alters the nutritional landscape of the gut and can lead to the expansion of pathogenic populations. Pathogenic bacteria exploit microbiota-derived sources of carbon and nitrogen as nutrients and regulatory signals to promote their own growth and virulence. By eliciting inflammation, these bacteria alter the intestinal environment and use unique systems for respiration and metal acquisition to drive their expansion. Unravelling the interactions between the microbiota, the host and pathogenic bacteria will produce strategies for manipulating the microbiota against infectious diseases.

Exposure to visual cues of pathogen contagion changes preferences for masculinity and symmetry in opposite-sex faces.

PubMed

Little, Anthony C; DeBruine, Lisa M; Jones, Benedict C

2011-07-07

Evolutionary approaches to human attractiveness have documented several traits that are proposed to be attractive across individuals and cultures, although both cross-individual and cross-cultural variations are also often found. Previous studies show that parasite prevalence and mortality/health are related to cultural variation in preferences for attractive traits. Visual experience of pathogen cues may mediate such variable preferences. Here we showed individuals slideshows of images with cues to low and high pathogen prevalence and measured their visual preferences for face traits. We found that both men and women moderated their preferences for facial masculinity and symmetry according to recent experience of visual cues to environmental pathogens. Change in preferences was seen mainly for opposite-sex faces, with women preferring more masculine and more symmetric male faces and men preferring more feminine and more symmetric female faces after exposure to pathogen cues than when not exposed to such cues. Cues to environmental pathogens had no significant effects on preferences for same-sex faces. These data complement studies of cross-cultural differences in preferences by suggesting a mechanism for variation in mate preferences. Similar visual experience could lead to within-cultural agreement and differing visual experience could lead to cross-cultural variation. Overall, our data demonstrate that preferences can be strategically flexible according to recent visual experience with pathogen cues. Given that cues to pathogens may signal an increase in contagion/mortality risk, it may be adaptive to shift visual preferences in favour of proposed good-gene markers in environments where such cues are more evident.

Exposure to visual cues of pathogen contagion changes preferences for masculinity and symmetry in opposite-sex faces

PubMed Central

Little, Anthony C.; DeBruine, Lisa M.; Jones, Benedict C.

2011-01-01

Evolutionary approaches to human attractiveness have documented several traits that are proposed to be attractive across individuals and cultures, although both cross-individual and cross-cultural variations are also often found. Previous studies show that parasite prevalence and mortality/health are related to cultural variation in preferences for attractive traits. Visual experience of pathogen cues may mediate such variable preferences. Here we showed individuals slideshows of images with cues to low and high pathogen prevalence and measured their visual preferences for face traits. We found that both men and women moderated their preferences for facial masculinity and symmetry according to recent experience of visual cues to environmental pathogens. Change in preferences was seen mainly for opposite-sex faces, with women preferring more masculine and more symmetric male faces and men preferring more feminine and more symmetric female faces after exposure to pathogen cues than when not exposed to such cues. Cues to environmental pathogens had no significant effects on preferences for same-sex faces. These data complement studies of cross-cultural differences in preferences by suggesting a mechanism for variation in mate preferences. Similar visual experience could lead to within-cultural agreement and differing visual experience could lead to cross-cultural variation. Overall, our data demonstrate that preferences can be strategically flexible according to recent visual experience with pathogen cues. Given that cues to pathogens may signal an increase in contagion/mortality risk, it may be adaptive to shift visual preferences in favour of proposed good-gene markers in environments where such cues are more evident. PMID:21123269

Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens.

PubMed

Mora, Marirosa; Bensi, Giuliano; Capo, Sabrina; Falugi, Fabiana; Zingaretti, Chiara; Manetti, Andrea G O; Maggi, Tiziana; Taddei, Anna Rita; Grandi, Guido; Telford, John L

2005-10-25

Although pili have long been recognized in Gram-negative pathogens as important virulence factors involved in adhesion and invasion, very little is known about extended surface organelles in Gram-positive pathogens. Here we report that Group A Streptococcus (GAS), a Gram-positive human-specific pathogen that causes pharyngitis, impetigo, invasive disease, necrotizing fasciitis, and autoimmune sequelae has long, surface-exposed, pilus-like structures composed of members of a family of extracellular matrix-binding proteins. We describe four variant pili and show that each is recognized by a specific serum of the Lancefield T-typing system, which has been used for over five decades to characterize GAS isolates. Furthermore, we show that immunization of mice with a combination of recombinant pilus proteins confers protection against mucosal challenge with virulent GAS bacteria. The data indicate that induction of a protective immune response against these structures may be a useful strategy for development of a vaccine against disease caused by GAS infection.

Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae from Arabidopsis leaves for stage-specific transcriptome analysis.

PubMed

Takahara, Hiroyuki; Dolf, Andreas; Endl, Elmar; O'Connell, Richard

2009-08-01

Generation of stage-specific cDNA libraries is a powerful approach to identify pathogen genes that are differentially expressed during plant infection. Biotrophic pathogens develop specialized infection structures inside living plant cells, but sampling the transcriptome of these structures is problematic due to the low ratio of fungal to plant RNA, and the lack of efficient methods to isolate them from infected plants. Here we established a method, based on fluorescence-activated cell sorting (FACS), to purify the intracellular biotrophic hyphae of Colletotrichum higginsianum from homogenates of infected Arabidopsis leaves. Specific selection of viable hyphae using a fluorescent vital marker provided intact RNA for cDNA library construction. Pilot-scale sequencing showed that the library was enriched with plant-induced and pathogenicity-related fungal genes, including some encoding small, soluble secreted proteins that represent candidate fungal effectors. The high purity of the hyphae (94%) prevented contamination of the library by sequences derived from host cells or other fungal cell types. RT-PCR confirmed that genes identified in the FACS-purified hyphae were also expressed in planta. The method has wide applicability for isolating the infection structures of other plant pathogens, and will facilitate cell-specific transcriptome analysis via deep sequencing and microarray hybridization, as well as proteomic analyses.

Small-Angle X-Ray Scattering Analysis of the Bifunctional Antibiotic Resistance Enzyme Aminoglycoside (6′) Acetyltransferase-Ie/Aminoglycoside (2″) Phosphotransferase-Ia Reveals a Rigid Solution Structure

PubMed Central

Caldwell, Shane J.

2012-01-01

Aminoglycoside (6′) acetyltransferase-Ie/aminoglycoside (2″) phosphotransferase-Ia [AAC(6′)-Ie/APH(2″)-Ia] is one of the most problematic aminoglycoside resistance factors in clinical pathogens, conferring resistance to almost every aminoglycoside antibiotic available to modern medicine. Despite 3 decades of research, our understanding of the structure of this bifunctional enzyme remains limited. We used small-angle X-ray scattering (SAXS) to model the structure of this bifunctional enzyme in solution and to study the impact of substrate binding on the enzyme. It was observed that the enzyme adopts a rigid conformation in solution, where the N-terminal AAC domain is fixed to the C-terminal APH domain and not loosely tethered. The addition of acetyl-coenzyme A, coenzyme A, GDP, guanosine 5′-[β,γ-imido]triphosphate (GMPPNP), and combinations thereof to the protein resulted in only modest changes to the radius of gyration (RG) of the enzyme, which were not consistent with any large changes in enzyme structure upon binding. These results imply some selective advantage to the bifunctional enzyme beyond coexpression as a single polypeptide, likely linked to an improvement in enzymatic properties. We propose that the rigid structure contributes to improved electrostatic steering of aminoglycoside substrates toward the two active sites, which may provide such an advantage. PMID:22290965

Lagrangian coherent structures are associated with fluctuations in airborne microbial populations

NASA Astrophysics Data System (ADS)

Tallapragada, P.; Ross, S. D.; Schmale, D. G.

2011-09-01

Many microorganisms are advected in the lower atmosphere from one habitat to another with scales of motion being hundreds to thousands of kilometers. The concentration of these microbes in the lower atmosphere at a single geographic location can show rapid temporal changes. We used autonomous unmanned aerial vehicles equipped with microbe-sampling devices to collect fungi in the genus Fusarium 100 m above ground level at a single sampling location in Blacksburg, Virginia, USA. Some Fusarium species are important plant and animal pathogens, others saprophytes, and still others are producers of dangerous toxins. We correlated punctuated changes in the concentration of Fusarium to the movement of atmospheric transport barriers identified as finite-time Lyapunov exponent-based Lagrangian coherent structures (LCSs). An analysis of the finite-time Lyapunov exponent field for periods surrounding 73 individual flight collections of Fusarium showed a relationship between punctuated changes in concentrations of Fusarium and the passage times of LCSs, particularly repelling LCSs. This work has implications for understanding the atmospheric transport of invasive microbial species into previously unexposed regions and may contribute to information systems for pest management and disease control in the future.

Use of 16S rRNA sequencing and quantitative PCR to correlate venous leg ulcer bacterial bioburden dynamics with wound expansion, antibiotic therapy, and healing

PubMed Central

Sprockett, Daniel D.; Ammons, Christine G.; Tuttle, Marie S.

2016-01-01

Clinical diagnosis of infection in chronic wounds is currently limited to subjective clinical signs and culture-based methods that underestimate the complexity of wound microbial bioburden as revealed by DNA-based microbial identification methods. Here, we use 16S rRNA next generation sequencing and quantitative polymerase chain reaction to characterize weekly changes in bacterial load, community structure, and diversity associated with a chronic venous leg ulcer over the 15-week course of treatment and healing. Our DNA-based methods and detailed sampling scheme reveal that the bacterial bioburden of the wound is unexpectedly dynamic, including changes in the bacterial load and community structure that correlate with wound expansion, antibiotic therapy, and healing. We demonstrate that these multidimensional changes in bacterial bioburden can be summarized using swabs taken prior to debridement, and therefore, can be more easily collected serially than debridement or biopsy samples. Overall, this case illustrates the importance of detailed clinical indicators and longitudinal sampling to determine the pathogenic significance of chronic wound microbial dynamics and guide best use of antimicrobials for improvement of healing outcomes. PMID:25902876

Insights into animal and plant lectins with antimicrobial activities.

PubMed

Dias, Renata de Oliveira; Machado, Leandro Dos Santos; Migliolo, Ludovico; Franco, Octavio Luiz

2015-01-05

Lectins are multivalent proteins with the ability to recognize and bind diverse carbohydrate structures. The glyco -binding and diverse molecular structures observed in these protein classes make them a large and heterogeneous group with a wide range of biological activities in microorganisms, animals and plants. Lectins from plants and animals are commonly used in direct defense against pathogens and in immune regulation. This review focuses on sources of animal and plant lectins, describing their functional classification and tridimensional structures, relating these properties with biotechnological purposes, including antimicrobial activities. In summary, this work focuses on structural-functional elucidation of diverse lectin groups, shedding some light on host-pathogen interactions; it also examines their emergence as biotechnological tools through gene manipulation and development of new drugs.

Assessment of Climate Change and Vector-borne Diseases in the United States

NASA Astrophysics Data System (ADS)

Monaghan, A. J.; Beard, C. B.; Eisen, R. J.; Barker, C. M.; Garofalo, J.; Hahn, M.; Hayden, M.; Ogden, N.; Schramm, P.

2016-12-01

Vector-borne diseases are illnesses that are transmitted by vectors, which include mosquitoes, ticks, and fleas. The seasonality, distribution, and prevalence of vector-borne diseases are influenced significantly by climate factors, primarily high and low temperature extremes and precipitation patterns. In this presentation we summarize key findings from Chapter 5 ("Vector-borne Diseases") of the recently published USGCRP Scientific Assessment of the Impacts of Climate Change on Human Health in the United States. Climate change is expected to alter geographic and seasonal distributions of vectors and vector-borne diseases, leading to earlier activity and northward range expansion of ticks capable of carrying the bacteria that cause Lyme disease and other pathogens, and influencing the distribution, abundance and prevalence of infection in mosquitoes that transmit West Nile virus and other pathogens. The emergence or reemergence of vector-borne pathogens is also likely.

Gene flow between divergent cereal - and grass-specific lineages of the rice blast fungus Magnaporthe oryzae

USDA-ARS?s Scientific Manuscript database

Delineating species and epidemic lineages in fungal plant pathogens is critical to our understanding of disease emergence and the structure of fungal biodiversity, and also informs international regulatory decisions. Pyricularia oryzae (syn. Magnaporthe oryzae) is a multi-host pathogen that infects ...

Structure, Function, Interaction, Co-evolution of Rice Blast Resistance Genes

USDA-ARS?s Scientific Manuscript database

Rice blast disease caused by the fungal pathogen Magnaporthe oryzae is one of the most destructive rice diseases worldwide. Resistance (R) genes to blast encode proteins that detect pathogen signaling molecules encoded by M. oryzae avirulence (AVR) genes. R genes can be a single or a member of clu...

Diseases of pines caused by the pitch canker fungus

Treesearch

L. David Dwinell; Stephen W. Fraedrich; D. Adams

2001-01-01

Fusarium subglutinans f. sp. pini, the pitch canker fungus, causes a number of serious diseases of Pinus species. The pathogen infects a variety of vegetative and reproductive pine structures at different stages of maturity and produces a diversity of symptoms. When the pathogen infects the woody vegetative...

Structural, functional and immunogenic insights on Cu,Zn Superoxide Dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

USDA-ARS?s Scientific Manuscript database

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and he...

The theory and application of space microbiology: China's experiences in space experiments and beyond.

PubMed

Liu, Changting

2017-02-01

Microorganisms exhibit high adaptability to extreme environments of outer space via phenotypic and genetic changes. These changes may affect astronauts in the space environment as well as on Earth because mutant microbes will inevitably return with the spacecraft. However, the role and significance of these phenotypic changes and the underlying mechanisms are important unresolved questions in the field of space biology. By reviewing, especially the Chinese studies, we propose a space microbial molecular effect theory, that is, the space environment affects the nature of genes and the molecular structure of microorganisms to produce phenotypic changes. In this review, we discussed three basic theories for the research of space microbiology, including (1) space microbial pathogenicity and virulence mutations and the human mutualism theory; (2) space microbial drug-resistance mutations and metabolism associated with space pharmaceuticals theory; (3) space corrosion, microbial decontamination, and new materials technology theory. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein-protein interactions.

PubMed

Yates, Christopher M; Sternberg, Michael J E

2013-11-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. © 2013.

How anthropogenic changes may affect soil-borne parasite diversity? Plant-parasitic nematode communities associated with olive trees in Morocco as a case study.

PubMed

Ali, Nadine; Tavoillot, Johannes; Besnard, Guillaume; Khadari, Bouchaib; Dmowska, Ewa; Winiszewska, Grażyna; Fossati-Gaschignard, Odile; Ater, Mohammed; Aït Hamza, Mohamed; El Mousadik, Abdelhamid; El Oualkadi, Aïcha; Moukhli, Abdelmajid; Essalouh, Laila; El Bakkali, Ahmed; Chapuis, Elodie; Mateille, Thierry

2017-02-06

Plant-parasitic nematodes (PPN) are major crop pests. On olive (Olea europaea), they significantly contribute to economic losses in the top-ten olive producing countries in the world especially in nurseries and under cropping intensification. The diversity and the structure of PPN communities respond to environmental and anthropogenic forces. The olive tree is a good host plant model to understand the impact of such forces on PPN diversity since it grows according to different modalities (wild, feral and cultivated olives). A wide soil survey was conducted in several olive-growing regions in Morocco. The taxonomical and the functional diversity as well as the structures of PPN communities were described and then compared between non-cultivated (wild and feral forms) and cultivated (traditional and high-density olive cultivation) olives. A high diversity of PPN with the detection of 117 species and 47 genera was revealed. Some taxa were recorded for the first time on olive trees worldwide and new species were also identified. Anthropogenic factors (wild vs cultivated conditions) strongly impacted the PPN diversity and the functional composition of communities because the species richness, the local diversity and the evenness of communities significantly decreased and the abundance of nematodes significantly increased in high-density conditions. Furthermore, these conditions exhibited many more obligate and colonizer PPN and less persister PPN compared to non-cultivated conditions. Taxonomical structures of communities were also impacted: genera such as Xiphinema spp. and Heterodera spp. were dominant in wild olive, whereas harmful taxa such as Meloidogyne spp. were especially enhanced in high-density orchards. Olive anthropogenic practices reduce the PPN diversity in communities and lead to changes of the community structures with the development of some damaging nematodes. The study underlined the PPN diversity as a relevant indicator to assess community pathogenicity. That could be taken into account in order to design control strategies based on community rearrangements and interactions between species instead of reducing the most pathogenic species.

The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease

PubMed Central

Elson, Joanna L.; Smith, Paul M.; Greaves, Laura C.; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M.A.; Taylor, Robert W.; Vila-Sanjurjo, Antón

2015-01-01

Mitochondrial DNA mutations are well recognized as an important cause of disease, with over two hundred variants in the protein encoding and mt-tRNA genes associated with human disorders. In contrast, the two genes encoding the mitochondrial rRNAs (mt-rRNAs) have been studied in far less detail. This is because establishing the pathogenicity of mt-rRNA mutations is a major diagnostic challenge. Only two disease causing mutations have been identified at these loci, both mapping to the small subunit (SSU). On the large subunit (LSU), however, the evidence for the presence of pathogenic LSU mt-rRNA changes is particularly sparse. We have previously expanded the list of deleterious SSU mt-rRNA mutations by identifying highly disruptive base changes capable of blocking the activity of the mitoribosomal SSU. To do this, we used a new methodology named heterologous inferential analysis (HIA). The recent arrival of near-atomic-resolution structures of the human mitoribosomal LSU, has enhanced the power of our approach by permitting the analysis of the corresponding sites of mutation within their natural structural context. Here, we have used these tools to determine whether LSU mt-rRNA mutations found in the context of human disease and/or ageing could disrupt the function of the mitoribosomal LSU. Our results clearly show that, much like the for SSU mt-rRNA, LSU mt-rRNAs mutations capable of compromising the function of the mitoribosomal LSU are indeed present in clinical samples. Thus, our work constitutes an important contribution to an emerging view of the mitoribosome as an important element in human health. PMID:26349026

Soil Microbial Community Responses to Long-Term Global Change Factors in a California Grassland

NASA Astrophysics Data System (ADS)

Qin, K.; Peay, K.

2015-12-01

Soil fungal and bacterial communities act as mediators of terrestrial carbon and nutrient cycling, and interact with the aboveground plant community as both pathogens and mutualists. However, these soil microbial communities are sensitive to changes in their environment. A better understanding of the response of soil microbial communities to global change may help to predict future soil microbial diversity, and assist in creating more comprehensive models of terrestrial carbon and nutrient cycles. This study examines the effects of four global change factors (increased temperature, increased variability in precipitation, nitrogen deposition, and CO2 enrichment) on soil microbial communities at the Jasper Ridge Global Change Experiment (JRGCE), a full-factorial global change manipulative experiment on three hectares of California grassland. While similar studies have examined the effects of global change on soil microbial communities, few have manipulated more factors or been longer in duration than the JRGCE, which began field treatments in 1998. We find that nitrogen deposition, CO2 enrichment, and increased variability in precipitation significantly affect the structure of both fungal and bacterial communities, and explain more of the variation in the community structures than do local soil chemistry or aboveground plant community. Fungal richness is correlated positively with soil nitrogen content and negatively with soil water content. Arbuscular mycorrhizal fungi (AMF), which associate closely with herbaceous plants' roots and assist in nutrient uptake, decrease in both richness and relative abundance in elevated CO2 treatments.

Public Health Threat of New, Reemerging, and Neglected Zoonoses in the Industrialized World

PubMed Central

Cutler, Sally J.; Fooks, Anthony R.

2010-01-01

Microbiologic infections acquired from animals, known as zoonoses, pose a risk to public health. An estimated 60% of emerging human pathogens are zoonotic. Of these pathogens, >71% have wildlife origins. These pathogens can switch hosts by acquiring new genetic combinations that have altered pathogenic potential or by changes in behavior or socioeconomic, environmental, or ecologic characteristics of the hosts. We discuss causal factors that influence the dynamics associated with emergence or reemergence of zoonoses, particularly in the industrialized world, and highlight selected examples to provide a comprehensive view of their range and diversity. PMID:20031035

Pathogen-regulated genes in wheat isogenic lines differing in resistance to brown rust Puccinia triticina.

PubMed

Dmochowska-Boguta, Marta; Alaba, Sylwia; Yanushevska, Yuliya; Piechota, Urszula; Lasota, Elzbieta; Nadolska-Orczyk, Anna; Karlowski, Wojciech M; Orczyk, Waclaw

2015-10-05

Inoculation of wheat plants with Puccinia triticina (Pt) spores activates a wide range of host responses. Compatible Pt interaction with susceptible Thatcher plants supports all stages of the pathogen life cycle. Incompatible interaction with TcLr9 activates defense responses including oxidative burst and micronecrotic reactions associated with the pathogen's infection structures and leads to complete termination of pathogen development. These two contrasting host-pathogen interactions were a foundation for transcriptome analysis of incompatible wheat-Pt interaction. A suppression subtractive hybridization (SSH) library was constructed using cDNA from pathogen-inoculated susceptible Thatcher and resistant TcLr9 isogenic lines. cDNA represented steps of wheat-brown rust interactions: spore germination, haustorium mother cell (HMC) formation and micronecrotic reactions. All ESTs were clustered and validated by similarity search to wheat genome using BLASTn and sim4db tools. qRT-PCR was used to determine transcript levels of selected ESTs after inoculation in both lines. Out of 793 isolated cDNA clones, 183 were classified into 152 contigs. 89 cDNA clones and encoded proteins were functionally annotated and assigned to 5 Gene Ontology categories: catalytic activity 48 clones (54 %), binding 32 clones (36 %), transporter activity 6 clones (7 %), structural molecule activity 2 clones (2 %) and molecular transducer activity 1 clone (1 %). Detailed expression profiles of 8 selected clones were analyzed using the same plant-pathogen system. The strongest induction after pathogen infection and the biggest differences between resistant and susceptible interactions were detected for clones encoding wall-associated kinase (GenBank accession number JG969003), receptor with leucine-rich repeat domain (JG968955), putative serine/threonine protein kinase (JG968944), calcium-mediated signaling protein (JG968925) and 14-3-3 protein (JG968969). The SSH library represents transcripts regulated by pathogen infection during compatible and incompatible interactions of wheat with P. triticina. Annotation of selected clones confirms their putative roles in successive steps of plant-pathogen interactions. The transcripts can be categorized as defense-related due to their involvement in either basal defense or resistance through an R-gene mediated reaction. The possible involvement of selected clones in pathogen recognition and pathogen-induced signaling as well as resistance mechanisms such as cell wall enforcement, oxidative burst and micronecrotic reactions is discussed.

The crystal structure of the D-alanine-D-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding.

PubMed

Huynh, Kim-Hung; Hong, Myoung-ki; Lee, Clarice; Tran, Huyen-Thi; Lee, Sang Hee; Ahn, Yeh-Jin; Cha, Sun-Shin; Kang, Lin-Woo

2015-11-01

Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

FATE OF PATHOGENIC MICROORGANISMS IN SOIL

EPA Science Inventory

In order to forecast the effect of viruses contaminating the ground water supply, sorption of pathogens on soil and subsurface materials was studied. Considering that change in free energy for the process is directly proportional to the degree of sorption, a model has been develo...

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.

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.

Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

PubMed

Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

2017-01-01

Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

Riboregulators: Fine-Tuning Virulence in Shigella.

PubMed

Fris, Megan E; Murphy, Erin R

2016-01-01

Within the past several years, RNA-mediated regulation (ribo-regulation) has become increasingly recognized for its importance in controlling critical bacterial processes. Regulatory RNA molecules, or riboregulators, are perpetually responsive to changes within the micro-environment of a bacterium. Notably, several characterized riboregulators control virulence in pathogenic bacteria, as is the case for each riboregulator characterized to date in Shigella. The timing of virulence gene expression and the ability of the pathogen to adapt to rapidly changing environmental conditions is critical to the establishment and progression of infection by Shigella species; ribo-regulators mediate each of these important processes. This mini review will present the current state of knowledge regarding RNA-mediated regulation in Shigella by detailing the characterization and function of each identified riboregulator in these pathogens.

Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa.

PubMed

Seyedahmadi, Babak Jian; Rivolta, Carlo; Keene, Julia A; Berson, Eliot L; Dryja, Thaddeus P

2004-08-01

A screen of the entire coding region of the USH2A gene in 129 unrelated patients with Usher syndrome type II (USH2) and in 146 unrelated patients with non-syndromic autosomal recessive retinitis pigmentosa (ARRP) uncovered 54 different sequence variations, including 18 likely pathogenic mutations (13 frameshift, three nonsense, and two missense), 12 changes of uncertain pathogenicity (11 missense changes and one in-frame deletion), and 24 non-pathogenic rare variants or polymorphisms. Of the 18 likely pathogenic mutations, nine were novel. Among the USH2 patients, 50 (39%) had one or two likely pathogenic mutations. The most common mutant allele in USH2 patients was E767fs, which was found in 29 patients, including one homozygote. Among the ARRP patients, we found 17 (12%) with one or two likely pathogenic mutations. The most common mutant allele in ARRP patients was C759F and it was found in 10 patients. The C759F allele was also found in two USH2 patients; in neither of them was a change in the other allele found. The second most common mutant allele in both patient groups was L1447fs (found in 6/50 USH2 patients and 6/17 ARRP patients). Of the 50+17=67 patients with identified USH2A mutations, only one mutation in one allele was found in 41+12=53 (79%); the reason for the high proportion of patients with only one identified mutation is obscure. Our results indicate that USH2A mutations are found in about 7% of all cases of RP in North America, a frequency similar to the RPGR gene (8%) and the rhodopsin gene (10%).

Phylodynamics with Migration: A Computational Framework to Quantify Population Structure from Genomic Data.

PubMed

Kühnert, Denise; Stadler, Tanja; Vaughan, Timothy G; Drummond, Alexei J

2016-08-01

When viruses spread, outbreaks can be spawned in previously unaffected regions. Depending on the time and mode of introduction, each regional outbreak can have its own epidemic dynamics. The migration and phylodynamic processes are often intertwined and need to be taken into account when analyzing temporally and spatially structured virus data. In this article, we present a fully probabilistic approach for the joint reconstruction of phylodynamic history in structured populations (such as geographic structure) based on a multitype birth-death process. This approach can be used to quantify the spread of a pathogen in a structured population. Changes in epidemic dynamics through time within subpopulations are incorporated through piecewise constant changes in transmission parameters.We analyze a global human influenza H3N2 virus data set from a geographically structured host population to demonstrate how seasonal dynamics can be inferred simultaneously with the phylogeny and migration process. Our results suggest that the main migration path among the northern, tropical, and southern region represented in the sample analyzed here is the one leading from the tropics to the northern region. Furthermore, the time-dependent transmission dynamics between and within two HIV risk groups, heterosexuals and injecting drug users, in the Latvian HIV epidemic are investigated. Our analyses confirm that the Latvian HIV epidemic peaking around 2001 was mainly driven by the injecting drug user risk group. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Earlier occurrence and increased explanatory power of climate for the first incidence of potato late blight caused by Phytophthora infestans in Fennoscandia

PubMed Central

Wiik, Lars; Hannukkala, Asko; Andreasson, Erik; Chen, Deliang; Ou, Tinghai; Liljeroth, Erland; Lankinen, Åsa

2017-01-01

Background Late blight (caused by Phytophthora infestans) is a devastating potato disease that has been found to occur earlier in the season over the last decades in Fennoscandia. Up until now the reasons for this change have not been investigated. Possible explanations for this change are climate alterations, changes in potato production or changes in pathogen biology, such as increased fitness or changes in gene flow within P. infestans populations. The first incidence of late blight is of high economic importance since fungicidal applications should be typically applied two weeks before the first signs of late blight and are repeated on average once a week. Methods We use field observations of first incidence of late blight in experimental potato fields from five sites in Sweden and Finland covering a total of 30 years and investigate whether the earlier incidence of late blight can be related to the climate. Results We linked the field data to meteorological data and found that the previous assumption, used in common late blight models, that the disease only develops at relative humidity levels above 90% had to be rejected. Rather than the typically assumed threshold relationship between late blight disease development and relative humidity we found a linear relationship. Our model furthermore showed two distinct responses of late blight to climate. At the beginning of the observation time (in Sweden until the early 90s and in Finland until the 2000s) the link between climate and first incidence was very weak. However, for the remainder of the time period the link was highly significant, indicating a change in the biological properties of the pathogen which could for example be a change in the dominating reproduction mode or a physiological change in the response of the pathogen to climate. Conclusions The study shows that models used in decision support systems need to be checked and re-parametrized regularly to be able to capture changes in pathogen biology. While this study was performed with data from Fennoscandia this new pathogen biology and late blight might spread to (or already be present at) other parts of the world as well. The strong link between climate and first incidence together with the presented model offers a tool to assess late blight incidence in future climates. PMID:28558041

Earlier occurrence and increased explanatory power of climate for the first incidence of potato late blight caused by Phytophthora infestans in Fennoscandia.

PubMed

Lehsten, Veiko; Wiik, Lars; Hannukkala, Asko; Andreasson, Erik; Chen, Deliang; Ou, Tinghai; Liljeroth, Erland; Lankinen, Åsa; Grenville-Briggs, Laura

2017-01-01

Late blight (caused by Phytophthora infestans) is a devastating potato disease that has been found to occur earlier in the season over the last decades in Fennoscandia. Up until now the reasons for this change have not been investigated. Possible explanations for this change are climate alterations, changes in potato production or changes in pathogen biology, such as increased fitness or changes in gene flow within P. infestans populations. The first incidence of late blight is of high economic importance since fungicidal applications should be typically applied two weeks before the first signs of late blight and are repeated on average once a week. We use field observations of first incidence of late blight in experimental potato fields from five sites in Sweden and Finland covering a total of 30 years and investigate whether the earlier incidence of late blight can be related to the climate. We linked the field data to meteorological data and found that the previous assumption, used in common late blight models, that the disease only develops at relative humidity levels above 90% had to be rejected. Rather than the typically assumed threshold relationship between late blight disease development and relative humidity we found a linear relationship. Our model furthermore showed two distinct responses of late blight to climate. At the beginning of the observation time (in Sweden until the early 90s and in Finland until the 2000s) the link between climate and first incidence was very weak. However, for the remainder of the time period the link was highly significant, indicating a change in the biological properties of the pathogen which could for example be a change in the dominating reproduction mode or a physiological change in the response of the pathogen to climate. The study shows that models used in decision support systems need to be checked and re-parametrized regularly to be able to capture changes in pathogen biology. While this study was performed with data from Fennoscandia this new pathogen biology and late blight might spread to (or already be present at) other parts of the world as well. The strong link between climate and first incidence together with the presented model offers a tool to assess late blight incidence in future climates.

PIOX, a new pathogen-induced oxygenase with homology to animal cyclooxygenase.

PubMed

Sanz, A; Moreno, J I; Castresana, C

1998-09-01

Changes in gene expression induced in tobacco leaves by the harpin HrpN protein elicitor were examined, and a new cDNA, piox (for pathogen-induced oxygenase), with homology to genes encoding cyclooxygenase or prostaglandin endoperoxide synthase (PGHS), was identified. In addition to the amino acid identity determined, the protein encoded by piox is predicted to have a structural core similar to that of ovine PGHS-1. Moreover, studies of protein functionality demonstrate that the PIOX recombinant protein possesses at least one of the two enzymatic activities of PGHSs, that of catalyzing the oxygenation of polyunsaturated fatty acids. piox transcripts accumulated after protein elicitor treatment or inoculation with bacteria. Expression of piox was induced in tissues responding to inoculation with both incompatible and compatible bacteria, but RNA and protein accumulation differed for both types of interactions. We show that expression of piox is rapidly induced in response to various cellular signals mediating plant responses to pathogen infection and that activation of piox expression is most likely related to the oxidative burst that takes place during the cell death processes examined. Cyclooxygenase catalyzes the first committed step in the formation of prostaglandins and thromboxanes, which are lipid-derived signal molecules that mediate many cellular processes, including the immune response in vertebrates. The finding of tobacco PIOX suggests that more similarities than hitherto expected will be found between the lipid-based responses for plant and animal systems.

Prediction of molecular mimicry candidates in human pathogenic bacteria.

PubMed

Doxey, Andrew C; McConkey, Brendan J

2013-08-15

Molecular mimicry of host proteins is a common strategy adopted by bacterial pathogens to interfere with and exploit host processes. Despite the availability of pathogen genomes, few studies have attempted to predict virulence-associated mimicry relationships directly from genomic sequences. Here, we analyzed the proteomes of 62 pathogenic and 66 non-pathogenic bacterial species, and screened for the top pathogen-specific or pathogen-enriched sequence similarities to human proteins. The screen identified approximately 100 potential mimicry relationships including well-characterized examples among the top-scoring hits (e.g., RalF, internalin, yopH, and others), with about 1/3 of predicted relationships supported by existing literature. Examination of homology to virulence factors, statistically enriched functions, and comparison with literature indicated that the detected mimics target key host structures (e.g., extracellular matrix, ECM) and pathways (e.g., cell adhesion, lipid metabolism, and immune signaling). The top-scoring and most widespread mimicry pattern detected among pathogens consisted of elevated sequence similarities to ECM proteins including collagens and leucine-rich repeat proteins. Unexpectedly, analysis of the pathogen counterparts of these proteins revealed that they have evolved independently in different species of bacterial pathogens from separate repeat amplifications. Thus, our analysis provides evidence for two classes of mimics: complex proteins such as enzymes that have been acquired by eukaryote-to-pathogen horizontal transfer, and simpler repeat proteins that have independently evolved to mimic the host ECM. Ultimately, computational detection of pathogen-specific and pathogen-enriched similarities to host proteins provides insights into potentially novel mimicry-mediated virulence mechanisms of pathogenic bacteria.

Prediction of molecular mimicry candidates in human pathogenic bacteria

PubMed Central

Doxey, Andrew C; McConkey, Brendan J

2013-01-01

Molecular mimicry of host proteins is a common strategy adopted by bacterial pathogens to interfere with and exploit host processes. Despite the availability of pathogen genomes, few studies have attempted to predict virulence-associated mimicry relationships directly from genomic sequences. Here, we analyzed the proteomes of 62 pathogenic and 66 non-pathogenic bacterial species, and screened for the top pathogen-specific or pathogen-enriched sequence similarities to human proteins. The screen identified approximately 100 potential mimicry relationships including well-characterized examples among the top-scoring hits (e.g., RalF, internalin, yopH, and others), with about 1/3 of predicted relationships supported by existing literature. Examination of homology to virulence factors, statistically enriched functions, and comparison with literature indicated that the detected mimics target key host structures (e.g., extracellular matrix, ECM) and pathways (e.g., cell adhesion, lipid metabolism, and immune signaling). The top-scoring and most widespread mimicry pattern detected among pathogens consisted of elevated sequence similarities to ECM proteins including collagens and leucine-rich repeat proteins. Unexpectedly, analysis of the pathogen counterparts of these proteins revealed that they have evolved independently in different species of bacterial pathogens from separate repeat amplifications. Thus, our analysis provides evidence for two classes of mimics: complex proteins such as enzymes that have been acquired by eukaryote-to-pathogen horizontal transfer, and simpler repeat proteins that have independently evolved to mimic the host ECM. Ultimately, computational detection of pathogen-specific and pathogen-enriched similarities to host proteins provides insights into potentially novel mimicry-mediated virulence mechanisms of pathogenic bacteria. PMID:23715053

A decision support tool to compare waterborne and foodborne infection and/or illness risks associated with climate change.

PubMed

Schijven, Jack; Bouwknegt, Martijn; de Roda Husman, Ana Maria; Rutjes, Saskia; Sudre, Bertrand; Suk, Jonathan E; Semenza, Jan C

2013-12-01

Climate change may impact waterborne and foodborne infectious disease, but to what extent is uncertain. Estimating climate-change-associated relative infection risks from exposure to viruses, bacteria, or parasites in water or food is critical for guiding adaptation measures. We present a computational tool for strategic decision making that describes the behavior of pathogens using location-specific input data under current and projected climate conditions. Pathogen-pathway combinations are available for exposure to norovirus, Campylobacter, Cryptosporidium, and noncholera Vibrio species via drinking water, bathing water, oysters, or chicken fillets. Infection risk outcomes generated by the tool under current climate conditions correspond with those published in the literature. The tool demonstrates that increasing temperatures lead to increasing risks for infection with Campylobacter from consuming raw/undercooked chicken fillet and for Vibrio from water exposure. Increasing frequencies of drought generally lead to an elevated infection risk of exposure to persistent pathogens such as norovirus and Cryptosporidium, but decreasing risk of exposure to rapidly inactivating pathogens, like Campylobacter. The opposite is the case with increasing annual precipitation; an upsurge of heavy rainfall events leads to more peaks in infection risks in all cases. The interdisciplinary tool presented here can be used to guide climate change adaptation strategies focused on infectious diseases. © 2013 Society for Risk Analysis.

Full genome comparison and characterization of avian H10 viruses with different pathogenicity in Mink (Mustela vison) reveals genetic and functional differences in the non-structural gene

PubMed Central

2010-01-01

Background The unique property of some avian H10 viruses, particularly the ability to cause severe disease in mink without prior adaptation, enabled our study. Coupled with previous experimental data and genetic characterization here we tried to investigate the possible influence of different genes on the virulence of these H10 avian influenza viruses in mink. Results Phylogenetic analysis revealed a close relationship between the viruses studied. Our study also showed that there are no genetic differences in receptor specificity or the cleavability of the haemagglutinin proteins of these viruses regardless of whether they are of low or high pathogenicity in mink. In poly I:C stimulated mink lung cells the NS1 protein of influenza A virus showing high pathogenicity in mink down regulated the type I interferon promoter activity to a greater extent than the NS1 protein of the virus showing low pathogenicity in mink. Conclusions Differences in pathogenicity and virulence in mink between these strains could be related to clear amino acid differences in the non structural 1 (NS1) protein. The NS gene of mink/84 appears to have contributed to the virulence of the virus in mink by helping the virus evade the innate immune responses. PMID:20591155

Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses

PubMed Central

Pappalardo, Morena; Juliá, Miguel; Howard, Mark J.; Rossman, Jeremy S.; Michaelis, Martin; Wass, Mark N.

2016-01-01

Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission. PMID:27009368

Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses.

PubMed

Pappalardo, Morena; Juliá, Miguel; Howard, Mark J; Rossman, Jeremy S; Michaelis, Martin; Wass, Mark N

2016-03-24

Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission.

Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

PubMed

Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

2011-09-01

The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

Structure-informed insights for NLR functioning in plant immunity.

PubMed

Sukarta, Octavina C A; Slootweg, Erik J; Goverse, Aska

2016-08-01

To respond to foreign invaders, plants have evolved a cell autonomous multilayered immune system consisting of extra- and intracellular immune receptors. Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) mediate recognition of pathogen effectors inside the cell and trigger a host specific defense response, often involving controlled cell death. NLRs consist of a central nucleotide-binding domain, which is flanked by an N-terminal CC or TIR domain and a C-terminal leucine-rich repeat domain (LRR). These multidomain proteins function as a molecular switch and their activity is tightly controlled by intra and inter-molecular interactions. In contrast to metazoan NLRs, the structural basis underlying NLR functioning as a pathogen sensor and activator of immune responses in plants is largely unknown. However, the first crystal structures of a number of plant NLR domains were recently obtained. In addition, biochemical and structure-informed analyses revealed novel insights in the cooperation between NLR domains and the formation of pre- and post activation complexes, including the coordinated activity of NLR pairs as pathogen sensor and executor of immune responses. Moreover, the discovery of novel integrated domains underscores the structural diversity of NLRs and provides alternative models for how these immune receptors function in plants. In this review, we will highlight these recent advances to provide novel insights in the structural, biochemical and molecular aspects involved in plant NLR functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus: differences from other mycobacterial isoforms and implications for selective inhibition.

PubMed

Cocaign, Angélique; Kubiak, Xavier; Xu, Ximing; Garnier, Guillaume; Li de la Sierra-Gallay, Inès; Chi-Bui, Linh; Dairou, Julien; Busi, Florent; Abuhammad, Areej; Haouz, Ahmed; Dupret, Jean Marie; Herrmann, Jean Louis; Rodrigues-Lima, Fernando

2014-11-01

Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is one of the most resistant organisms to chemotherapeutic agents. However, structural and functional studies of M. abscessus proteins that could modify/inactivate antibiotics remain nonexistent. Here, the structural and functional characterization of an arylamine N-acetyltransferase (NAT) from M. abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays significant N-acetyltransferase activity towards aromatic substrates, including antibiotics such as isoniazid and p-aminosalicylate. The enzyme is endogenously expressed and functional in both the rough and smooth M. abscessus morphotypes. The crystal structure of (MYCAB)NAT1 at 1.8 Å resolution reveals that it is more closely related to Nocardia farcinica NAT than to mycobacterial isoforms. In particular, structural and physicochemical differences from other mycobacterial NATs were found in the active site. Peculiarities of (MYCAB)NAT1 were further supported by kinetic and docking studies showing that the enzyme was poorly inhibited by the piperidinol inhibitor of mycobacterial NATs. This study describes the first structure of an antibiotic-modifying enzyme from M. abscessus and provides bases to better understand the substrate/inhibitor-binding specificities among mycobacterial NATs and to identify/optimize specific inhibitors. These data should also contribute to the understanding of the mechanisms that are responsible for the pathogenicity and extensive chemotherapeutic resistance of M. abscessus.

The genetic structure of a Venturia inaequalis population in a heterogeneous host population composed of different Malus species

PubMed Central

2013-01-01

Background Adaptation, which induces differentiation between populations in relation to environmental conditions, can initiate divergence. The balance between gene flow and selection determines the maintenance of such a structure in sympatry. Studying these two antagonistic forces in plant pathogens is made possible because of the high ability of pathogens to disperse and of the strong selective pressures exerted by their hosts. In this article, we analysed the genetic structure of the population of the apple scab fungus, Venturia inaequalis, in a heterogeneous environment composed of various Malus species. Inferences were drawn from microsatellite and AFLP data obtained from 114 strains sampled in a single orchard on nine different Malus species to determine the forces that shape the genetic structure of the pathogen. Results Using clustering methods, we first identified two specialist subpopulations: (i) a virulent subpopulation sampled on Malus trees carrying the Rvi6 resistance gene; and (ii) a subpopulation infecting only Malus trees that did not carry this resistance gene. A genome scan of loci on these two subpopulations did not detect any locus under selection. Additionally, we did not detect any other particular substructure linked to different hosts. However, an isolation-by-distance (IBD) pattern at the orchard scale revealed free gene flow within each subpopulation. Conclusions Our work shows a rare example of a very strong effect of a resistance gene on pathogen populations. Despite the high diversity of Malus hosts, the presence of Rvi6 seems sufficient to explain the observed genetic structure. Moreover, detection of an IBD pattern at the orchard scale revealed a very low average dispersal distance that is particularly significant for epidemiologists and landscape managers for the design of scab control strategies PMID:23497223

Salmonella—how a metabolic generalist adopts an intracellular lifestyle during infection

PubMed Central

Dandekar, Thomas; Fieselmann, Astrid; Fischer, Eva; Popp, Jasmin; Hensel, Michael; Noster, Janina

2015-01-01

The human-pathogenic bacterium Salmonella enterica adjusts and adapts to different environments while attempting colonization. In the course of infection nutrient availabilities change drastically. New techniques, “-omics” data and subsequent integration by systems biology improve our understanding of these changes. We review changes in metabolism focusing on amino acid and carbohydrate metabolism. Furthermore, the adaptation process is associated with the activation of genes of the Salmonella pathogenicity islands (SPIs). Anti-infective strategies have to take these insights into account and include metabolic and other strategies. Salmonella infections will remain a challenge for infection biology. PMID:25688337

Analysis of the biofilm proteome of Xylella fastidiosa.

PubMed

Silva, Mariana S; De Souza, Alessandra A; Takita, Marco A; Labate, Carlos A; Machado, Marcos A

2011-09-22

Xylella fastidiosa is limited to the xylem of the plant host and the foregut of insect vectors (sharpshooters). The mechanism of pathogenicity of this bacterium differs from other plant pathogens, since it does not present typical genes that confer specific interactions between plant and pathogens (avr and/or hrp). The bacterium is injected directly into the xylem vessels where it adheres and colonizes. The whole process leads to the formation of biofilms, which are considered the main mechanism of pathogenicity. Cells in biofilms are metabolically and phenotypically different from their planktonic condition. The mature biofilm stage (phase of higher cell density) presents high virulence and resistance to toxic substances such as antibiotics and detergents. Here we performed proteomic analysis of proteins expressed exclusively in the mature biofilm of X. fastidiosa strain 9a5c, in comparison to planktonic growth condition. We found a total of 456 proteins expressed in the biofilm condition, which correspond to approximately 10% of total protein in the genome. The biofilm showed 37% (or 144 proteins) different protein than we found in the planktonic growth condition. The large difference in protein pattern in the biofilm condition may be responsible for the physiological changes of the cells in the biofilm of X. fastidiosa. Mass spectrometry was used to identify these proteins, while real-time quantitative polymerase chain reaction monitored expression of genes encoding them. Most of proteins expressed in the mature biofilm growth were associated with metabolism, adhesion, pathogenicity and stress conditions. Even though the biofilm cells in this work were not submitted to any stress condition, some stress related proteins were expressed only in the biofilm condition, suggesting that the biofilm cells would constitutively express proteins in different adverse environments. We observed overexpression of proteins related to quorum sensing, proving the existence of communication between cells, and thus the development of structuring the biofilm (mature biofilm) leading to obstruction of vessels and development of disease. This paper reports a first proteomic analysis of mature biofilm of X. fastidiosa, opening new perspectives for understanding the biochemistry of mature biofilm growth in a plant pathogen.

Analysis of the biofilm proteome of Xylella fastidiosa

PubMed Central

2011-01-01

Background Xylella fastidiosa is limited to the xylem of the plant host and the foregut of insect vectors (sharpshooters). The mechanism of pathogenicity of this bacterium differs from other plant pathogens, since it does not present typical genes that confer specific interactions between plant and pathogens (avr and/or hrp). The bacterium is injected directly into the xylem vessels where it adheres and colonizes. The whole process leads to the formation of biofilms, which are considered the main mechanism of pathogenicity. Cells in biofilms are metabolically and phenotypically different from their planktonic condition. The mature biofilm stage (phase of higher cell density) presents high virulence and resistance to toxic substances such as antibiotics and detergents. Here we performed proteomic analysis of proteins expressed exclusively in the mature biofilm of X. fastidiosa strain 9a5c, in comparison to planktonic growth condition. Results We found a total of 456 proteins expressed in the biofilm condition, which correspond to approximately 10% of total protein in the genome. The biofilm showed 37% (or 144 proteins) different protein than we found in the planktonic growth condition. The large difference in protein pattern in the biofilm condition may be responsible for the physiological changes of the cells in the biofilm of X. fastidiosa. Mass spectrometry was used to identify these proteins, while real-time quantitative polymerase chain reaction monitored expression of genes encoding them. Most of proteins expressed in the mature biofilm growth were associated with metabolism, adhesion, pathogenicity and stress conditions. Even though the biofilm cells in this work were not submitted to any stress condition, some stress related proteins were expressed only in the biofilm condition, suggesting that the biofilm cells would constitutively express proteins in different adverse environments. Conclusions We observed overexpression of proteins related to quorum sensing, proving the existence of communication between cells, and thus the development of structuring the biofilm (mature biofilm) leading to obstruction of vessels and development of disease. This paper reports a first proteomic analysis of mature biofilm of X. fastidiosa, opening new perspectives for understanding the biochemistry of mature biofilm growth in a plant pathogen. PMID:21939513

Antifungal activity of various essential oils against Rhizoctonia solani and Macrophomina phaseolina as major bean pathogens.

PubMed

Khaledi, N; Taheri, P; Tarighi, S

2015-03-01

The main objective of this study was to investigate the effect of various essential oils (EOs) to decrease the activity of cell wall degrading enzymes (CWDEs) produced by fungal phytopathogens, which are associated with disease progress. Also, effect of seed treatment and foliar application of peppermint EO and its main constituent, menthol, on diseases caused by two necrotrophic pathogens on bean was investigated. Antifungal activity of EOs on Rhizoctonia solani and Macrophomina phaseolina, as bean pathogens, was evaluated. The EOs of Mentha piperita, Bunium persicum and Thymus vulgaris revealed the highest antifungal activity against fungi. The EO of M. piperita had the lowest minimum inhibitory concentration (MIC) for R. solani among the three EOs tested. This pathogen did not grow in the presence of M. piperita, B. persicum and T. vulgaris EOs at 850, 1200 and 1100 ppm concentrations, respectively. The B. persicum EO had the lowest MIC for M. phaseolina as this fungus did not grow in the presence of M. piperita, B. persicum and T. vulgaris EOs at concentrations of 975, 950 and 1150 ppm, respectively. Hyphae exposed to EOs showed structural changes. Activities of cellulase and pectinase, as main CWDEs of pathogens, decreased by EOs at low concentration without effect on fungal growth. Seed treatment and foliar application of peppermint EO and/or menthol significantly reduced the development of bean diseases caused by both fungi. Higher capability of menthol than peppermint EO in decreasing diseases on bean was observed. Reducing CDWEs activity is a mechanism of EOs' effect on fungi. Higher antifungal activity of menthol compared to peppermint EO was observed not only in vitro but also in vivo. Effect of EOs on CWDEs involved in pathogenesis is described in this study for the first time. Menthol can be used as a botanical fungicide to control destructive fungal diseases on bean. © 2014 The Society for Applied Microbiology.

Linking microbial community structure to function in representative simulated systems.

PubMed

Marcus, Ian M; Wilder, Hailey A; Quazi, Shanin J; Walker, Sharon L

2013-04-01

Pathogenic bacteria are generally studied as a single strain under ideal growing conditions, although these conditions are not the norm in the environments in which pathogens typically proliferate. In this investigation, a representative microbial community along with Escherichia coli O157:H7, a model pathogen, was studied in three environments in which such a pathogen could be found: a human colon, a septic tank, and groundwater. Each of these systems was built in the lab in order to retain the physical/chemical and microbial complexity of the environments while maintaining control of the feed into the models. The microbial community in the colon was found to have a high percentage of bacteriodetes and firmicutes, while the septic tank and groundwater systems were composed mostly of proteobacteria. The introduction of E. coli O157:H7 into the simulated systems elicited a shift in the structures and phenotypic cell characteristics of the microbial communities. The fate and transport of the microbial community with E. coli O157:H7 were found to be significantly different from those of E. coli O157:H7 studied as a single isolate, suggesting that the behavior of the organism in the environment was different from that previously conceived. The findings in this study clearly suggest that to gain insight into the fate of pathogens, cells should be grown and analyzed under conditions simulating those of the environment in which the pathogens are present.

Linking Microbial Community Structure to Function in Representative Simulated Systems

PubMed Central

Marcus, Ian M.; Wilder, Hailey A.; Quazi, Shanin J.

2013-01-01

Pathogenic bacteria are generally studied as a single strain under ideal growing conditions, although these conditions are not the norm in the environments in which pathogens typically proliferate. In this investigation, a representative microbial community along with Escherichia coli O157:H7, a model pathogen, was studied in three environments in which such a pathogen could be found: a human colon, a septic tank, and groundwater. Each of these systems was built in the lab in order to retain the physical/chemical and microbial complexity of the environments while maintaining control of the feed into the models. The microbial community in the colon was found to have a high percentage of bacteriodetes and firmicutes, while the septic tank and groundwater systems were composed mostly of proteobacteria. The introduction of E. coli O157:H7 into the simulated systems elicited a shift in the structures and phenotypic cell characteristics of the microbial communities. The fate and transport of the microbial community with E. coli O157:H7 were found to be significantly different from those of E. coli O157:H7 studied as a single isolate, suggesting that the behavior of the organism in the environment was different from that previously conceived. The findings in this study clearly suggest that to gain insight into the fate of pathogens, cells should be grown and analyzed under conditions simulating those of the environment in which the pathogens are present. PMID:23396331