Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen.

PubMed

Bastidas, Robert J; Valdivia, Raphael H

2016-06-01

Chlamydia species infect millions of individuals worldwide and are important etiological agents of sexually transmitted disease, infertility, and blinding trachoma. Historically, the genetic intractability of this intracellular pathogen has hindered the molecular dissection of virulence factors contributing to its pathogenesis. The obligate intracellular life cycle of Chlamydia and restrictions on the use of antibiotics as selectable markers have impeded the development of molecular tools to genetically manipulate these pathogens. However, recent developments in the field have resulted in significant gains in our ability to alter the genome of Chlamydia, which will expedite the elucidation of virulence mechanisms. In this review, we discuss the challenges affecting the development of molecular genetic tools for Chlamydia and the work that laid the foundation for recent advancements in the genetic analysis of this recalcitrant pathogen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

When are pathogen genome sequences informative of transmission events?

PubMed Central

Ferguson, Neil; Jombart, Thibaut

2018-01-01

Recent years have seen the development of numerous methodologies for reconstructing transmission trees in infectious disease outbreaks from densely sampled whole genome sequence data. However, a fundamental and as of yet poorly addressed limitation of such approaches is the requirement for genetic diversity to arise on epidemiological timescales. Specifically, the position of infected individuals in a transmission tree can only be resolved by genetic data if mutations have accumulated between the sampled pathogen genomes. To quantify and compare the useful genetic diversity expected from genetic data in different pathogen outbreaks, we introduce here the concept of ‘transmission divergence’, defined as the number of mutations separating whole genome sequences sampled from transmission pairs. Using parameter values obtained by literature review, we simulate outbreak scenarios alongside sequence evolution using two models described in the literature to describe transmission divergence of ten major outbreak-causing pathogens. We find that while mean values vary significantly between the pathogens considered, their transmission divergence is generally very low, with many outbreaks characterised by large numbers of genetically identical transmission pairs. We describe the impact of transmission divergence on our ability to reconstruct outbreaks using two outbreak reconstruction tools, the R packages outbreaker and phybreak, and demonstrate that, in agreement with previous observations, genetic sequence data of rapidly evolving pathogens such as RNA viruses can provide valuable information on individual transmission events. Conversely, sequence data of pathogens with lower mean transmission divergence, including Streptococcus pneumoniae, Shigella sonnei and Clostridium difficile, provide little to no information about individual transmission events. Our results highlight the informational limitations of genetic sequence data in certain outbreak scenarios, and demonstrate the need to expand the toolkit of outbreak reconstruction tools to integrate other types of epidemiological data. PMID:29420641

Genetic Recombination between Human and Animal Parasites Creates Novel Strains of Human Pathogen

PubMed Central

Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

2015-01-01

Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228

Genetic recombination between human and animal parasites creates novel strains of human pathogen.

PubMed

Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

2015-03-01

Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.

Stable genetic diversity despite parasite and pathogen spread in honey bee colonies.

PubMed

Jara, Laura; Muñoz, Irene; Cepero, Almudena; Martín-Hernández, Raquel; Serrano, José; Higes, Mariano; De la Rúa, Pilar

2015-10-01

In the last decades, the rapid spread of diseases, such as varroosis and nosemosis, associated with massive honey bee colonies mortality around the world has significantly decreased the number and size of honey bee populations and possibly their genetic diversity. Here, we compare the genetic diversity of Iberian honey bee colonies in two samplings performed in 2006 and 2010 in relation to the presence of the pathogenic agents Nosema apis, Nosema ceranae, and Varroa destructor in order to determine whether parasite and pathogen spread in honey bee colonies reflects changes in genetic diversity. We found that the genetic diversity remained similar, while the incidence of N. ceranae increased and the incidence of N. apis and V. destructor decreased slightly. These results indicate that the genetic diversity was not affected by the presence of these pathogenic agents in the analyzed period. However, the two groups of colonies with and without Nosema/Varroa detected showed significant genetic differentiation (G test). A detailed analysis of the allelic segregation of microsatellite loci in Nosema/Varroa-negative colonies and parasitized ones revealed two outlier loci related to genes involved in immune response.

Stable genetic diversity despite parasite and pathogen spread in honey bee colonies

NASA Astrophysics Data System (ADS)

Jara, Laura; Muñoz, Irene; Cepero, Almudena; Martín-Hernández, Raquel; Serrano, José; Higes, Mariano; De la Rúa, Pilar

2015-10-01

In the last decades, the rapid spread of diseases, such as varroosis and nosemosis, associated with massive honey bee colonies mortality around the world has significantly decreased the number and size of honey bee populations and possibly their genetic diversity. Here, we compare the genetic diversity of Iberian honey bee colonies in two samplings performed in 2006 and 2010 in relation to the presence of the pathogenic agents Nosema apis, Nosema ceranae, and Varroa destructor in order to determine whether parasite and pathogen spread in honey bee colonies reflects changes in genetic diversity. We found that the genetic diversity remained similar, while the incidence of N. ceranae increased and the incidence of N. apis and V. destructor decreased slightly. These results indicate that the genetic diversity was not affected by the presence of these pathogenic agents in the analyzed period. However, the two groups of colonies with and without Nosema/Varroa detected showed significant genetic differentiation (G test). A detailed analysis of the allelic segregation of microsatellite loci in Nosema/Varroa-negative colonies and parasitized ones revealed two outlier loci related to genes involved in immune response.

Mastitis of periparturient Holstein cattle: a phenotypic and genetic study.

PubMed

Detilleux, J C; Kehrli, M E; Freeman, A E; Fox, L K; Kelley, D H

1995-10-01

Environmental and genetic factors affecting somatic cell scores, clinical mastitis, and IMI by minor and major pathogens were studied on 137 periparturient Holstein cows selected for milk production. Environmental effects were obtained by generalized least squares and logistic regression. Genetic parameters were from BLUP and threshold animal models. Lactation number affected the number of quarters with clinical mastitis and the number of quarters infected with minor pathogens. The DIM affected somatic cell score and number of quarters infected with major pathogens. Heritabilities for all mastitis indicators averaged 10%, but differences occurred among the indicators. Correlations between breeding values of the number of quarters infected with minor pathogens and the number infected with major pathogens were antagonistic and statistically significant.

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

PubMed Central

Zeng, Y.; Yin, T.; Brügemann, K.

2018-01-01

Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle. PMID:29608619

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.

Genetic islands in pome fruit pathogenic and non-pathogenic Erwinia species and related plasmids

PubMed Central

Llop, Pablo

2015-01-01

New pathogenic bacteria belonging to the genus Erwinia associated with pome fruit trees (Erwinia, E. piriflorinigrans, E. uzenensis) have been increasingly described in the last years, and comparative analyses have found that all these species share several genetic characteristics. Studies at different level (whole genome comparison, virulence genes, plasmid content, etc.) show a high intraspecies homogeneity (i.e., among E. amylovora strains) and also abundant similarities appear between the different Erwinia species: presence of plasmids of similar size in the pathogenic species; high similarity in several genes associated with exopolysaccharide production and hence, with virulence, as well as in some other genes, in the chromosomes. Many genetic similarities have been observed also among some of the plasmids (and genomes) from the pathogenic species and E. tasmaniensis or E. billingiae, two epiphytic species on the same hosts. The amount of genetic material shared in this genus varies from individual genes to clusters, genomic islands and genetic material that even may constitute a whole plasmid. Recent research on evolution of erwinias point out the horizontal transfer acquisition of some genomic islands that were subsequently lost in some species and several pathogenic traits that are still present. How this common material has been obtained and is efficiently maintained in different species belonging to the same genus sharing a common ecological niche provides an idea of the origin and evolution of the pathogenic Erwinia and the interaction with non-pathogenic species present in the same niche, and the role of the genes that are conserved in all of them. PMID:26379649

Population genetic analysis infers mMigration pathways of Phytophthora ramorum in US nurseries

Treesearch

Erica M. Goss; Meg Larsen; Gary A. Chastagner; Donald R. Givens; Niklaus J. Grünwald; Barbara Jane Howlett

2009-01-01

Recently introduced, exotic plant pathogens may exhibit low genetic diversity and be limited to clonal reproduction. However, rapidly mutating molecular markers such as microsatellites can reveal genetic variation within these populations and be used to model putative migration patterns. Phytophthora ramorum is the exotic pathogen, discovered in...

Genetic anaylsis of a disease resistance gene from loblolly pine

Treesearch

Yinghua Huang; Nili Jin; Alex Diner; Chuck Tauer; Yan Zhang; John Damicone

2003-01-01

Rapid advances in molecular genetics provide great opportunities for studies of host defense mechanisms. Examination of plant responses to disease at the cellular and molecular level permits both discovery of changes in gene expression in the tissues attacked by pathogens, and identification of genetic components involved in the interaction between host and pathogens....

A distributed national network for label-free rapid identification of emerging pathogens

NASA Astrophysics Data System (ADS)

Robinson, J. Paul; Rajwa, Bartek P.; Dundar, M. Murat; Bae, Euiwon; Patsekin, Valery; Hirleman, E. Daniel; Roumani, Ali; Bhunia, Arun K.; Dietz, J. Eric; Davisson, V. Jo; Thomas, John G.

2011-05-01

Typical bioterrorism prevention scenarios assume well-known and well-characterized pathogens like anthrax or tularemia, which are serious public concerns if released into food and/or water supplies or distributed using other vectors. Common governmental contingencies include rapid response to these biological threats with predefined treatments and management operations. However, bioterrorist attacks may follow a far more sophisticated route. With the widely known and immense progress in genetics and the availability of molecular biology tools worldwide, the potential for malicious modification of pathogenic genomes is very high. Common non-pathogenic microorganisms could be transformed into dangerous, debilitating pathogens. Known pathogens could also be modified to avoid detection, because organisms are traditionally identified on the basis of their known physiological or genetic properties. In the absence of defined primers a laboratory using genetic biodetection methods such as PCR might be unable to quickly identify a modified microorganism. Our concept includes developing a nationwide database of signatures based on biophysical (such as elastic light scattering (ELS) properties and/or Raman spectra) rather than genetic properties of bacteria. When paired with a machine-learning system for emerging pathogen detection these data become an effective detection system. The approach emphasizes ease of implementation using a standardized collection of phenotypic information and extraction of biophysical features of pathogens. Owing to the label-free nature of the detection modalities ELS is significantly less costly than any genotypic or mass spectrometry approach.

Quantitative Resistance: More Than Just Perception of a Pathogen

PubMed Central

2017-01-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. PMID:28302676

Equine behavioral enrichment toys as tools for non-invasive recovery of viral and host DNA.

PubMed

Seeber, Peter A; Soilemetzidou, Sanatana E; East, Marion L; Walzer, Chris; Greenwood, Alex D

2017-09-01

Direct collection of samples from wildlife can be difficult and sometimes impossible. Non-invasive remote sampling for the purpose of DNA extraction is a potential tool for monitoring the presence of wildlife at the individual level, and for identifying the pathogens shed by wildlife. Equine herpesviruses (EHV) are common pathogens of equids that can be fatal if transmitted to other mammals. Transmission usually occurs by nasal aerosol discharge from virus-shedding individuals. The aim of this study was to validate a simple, non-invasive method to track EHV shedding in zebras and to establish an efficient protocol for genotyping individual zebras from environmental DNA (eDNA). A commercially available horse enrichment toy was deployed in captive Grévy's, mountain, and plains zebra enclosures and swabbed after 4-24 hr. Using eDNA extracted from these swabs four EHV strains (EHV-1, EHV-7, wild ass herpesvirus and zebra herpesvirus) were detected by PCR and confirmed by sequencing, and 12 of 16 zebras present in the enclosures were identified as having interacted with the enrichment toy by mitochondrial DNA amplification and sequencing. We conclude that, when direct sampling is difficult or prohibited, non-invasive sampling of eDNA can be a useful tool to determine the genetics of individuals or populations and for detecting pathogen shedding in captive wildlife. © 2017 Wiley Periodicals, Inc.

Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

PubMed Central

Vercken, Elodie; Fontaine, Michael C.; Gladieux, Pierre; Hood, Michael E.; Jonot, Odile; Giraud, Tatiana

2010-01-01

Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns. PMID:21187901

Evolution and population genetics of exotic and reemerging pathogens: traditional and novel tools and approaches

Treesearch

N.J. Grünwald; E.M. Goss

2011-01-01

Given human population growth and accelerated global trade, the rate of emergence of exotic plant pathogens is bound to increase. Understanding the processes that lead to the emergence of new pathogens can help manage emerging epidemics. Novel tools for analyzing population genetic variation can be used to infer the evolutionary history of populations or species,...

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

PubMed Central

2011-01-01

Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness. PMID:21284886

Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity.

PubMed

Boyce, Walter M; Weisenberger, Mara E; Penedo, M Cecilia T; Johnson, Christine K

2011-02-01

A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

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...

The influence of genetic drift and selection on quantitative traits in a plant pathogenic fungus.

PubMed

Stefansson, Tryggvi S; McDonald, Bruce A; Willi, Yvonne

2014-01-01

Genetic drift and selection are ubiquitous evolutionary forces acting to shape genetic variation in populations. While their relative importance has been well studied in plants and animals, less is known about their relative importance in fungal pathogens. Because agro-ecosystems are more homogeneous environments than natural ecosystems, stabilizing selection may play a stronger role than genetic drift or diversifying selection in shaping genetic variation among populations of fungal pathogens in agro-ecosystems. We tested this hypothesis by conducting a QST/FST analysis using agricultural populations of the barley pathogen Rhynchosporium commune. Population divergence for eight quantitative traits (QST) was compared with divergence at eight neutral microsatellite loci (FST) for 126 pathogen strains originating from nine globally distributed field populations to infer the effects of genetic drift and types of selection acting on each trait. Our analyses indicated that five of the eight traits had QST values significantly lower than FST, consistent with stabilizing selection, whereas one trait, growth under heat stress (22°C), showed evidence of diversifying selection and local adaptation (QST>FST). Estimates of heritability were high for all traits (means ranging between 0.55-0.84), and average heritability across traits was negatively correlated with microsatellite gene diversity. Some trait pairs were genetically correlated and there was significant evidence for a trade-off between spore size and spore number, and between melanization and growth under benign temperature. Our findings indicate that many ecologically and agriculturally important traits are under stabilizing selection in R. commune and that high within-population genetic variation is maintained for these traits.

Population Genetic Analysis Infers Migration Pathways of Phytophthora ramorum in US Nurseries

PubMed Central

Goss, Erica M.; Larsen, Meg; Chastagner, Gary A.; Givens, Donald R.; Grünwald, Niklaus J.

2009-01-01

Recently introduced, exotic plant pathogens may exhibit low genetic diversity and be limited to clonal reproduction. However, rapidly mutating molecular markers such as microsatellites can reveal genetic variation within these populations and be used to model putative migration patterns. Phytophthora ramorum is the exotic pathogen, discovered in the late 1990s, that is responsible for sudden oak death in California forests and ramorum blight of common ornamentals. The nursery trade has moved this pathogen from source populations on the West Coast to locations across the United States, thus risking introduction to other native forests. We examined the genetic diversity of P. ramorum in United States nurseries by microsatellite genotyping 279 isolates collected from 19 states between 2004 and 2007. Of the three known P. ramorum clonal lineages, the most common and genetically diverse lineage in the sample was NA1. Two eastward migration pathways were revealed in the clustering of NA1 isolates into two groups, one containing isolates from Connecticut, Oregon, and Washington and the other isolates from California and the remaining states. This finding is consistent with trace forward analyses conducted by the US Department of Agriculture's Animal and Plant Health Inspection Service. At the same time, genetic diversities in several states equaled those observed in California, Oregon, and Washington and two-thirds of multilocus genotypes exhibited limited geographic distributions, indicating that mutation was common during or subsequent to migration. Together, these data suggest that migration, rapid mutation, and genetic drift all play a role in structuring the genetic diversity of P. ramorum in US nurseries. This work demonstrates that fast-evolving genetic markers can be used to examine the evolutionary processes acting on recently introduced pathogens and to infer their putative migration patterns, thus showing promise for the application of forensics to plant pathogens. PMID:19774068

Influence of landscape and social interactions on transmission of disease in a social cervid.

PubMed

Vander Wal, Eric; Paquet, Paul C; Andrés, José A

2012-03-01

The mechanisms of pathogen transmission are often social behaviours. These occur at local scales and are affected by landscape-scale population structure. Host populations frequently exist in patchy and isolated environments that create a continuum of genetic and social familiarity. Such variability has an important multispatial effect on pathogen spread. We assessed elk dispersal (i.e. likelihood of interdeme pathogen transmission) through spatially explicit genetic analyses. At a landscape scale, the elk population was composed of one cluster within a southeast-to-northwest cline spanning three spatially discrete subpopulations of elk across two protected areas in Manitoba (Canada). Genetic data are consistent with spatial variability in apparent prevalence of bovine tuberculosis (TB) in elk. Given the existing population structure, between-subpopulation spread of disease because of elk dispersal is unlikely. Furthermore, to better understand the risk of spread and distribution of the TB, we used a combination of close-contact logging biotelemetry and genetic data, which highlights how social intercourse may affect pathogen transmission. Our results indicate that close-contact interaction rate and duration did not covary with genetic relatedness. Thus, direct elk-to-elk transmission of disease is unlikely to be constrained to related individuals. That social intercourse in elk is not limited to familial groups provides some evidence pathogen transmission may be density-dependent. We show that the combination of landscape-scale genetics, relatedness and local-scale social behaviours is a promising approach to understand and predict landscape-level pathogen transmission within our system and within all social ungulate systems affected by transmissible diseases. © 2012 Blackwell Publishing Ltd.

Deconstructing host-pathogen interactions in Drosophila

PubMed Central

Bier, Ethan; Guichard, Annabel

2012-01-01

Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. PMID:21979942

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...

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

PubMed Central

Eshbaugh, Robert; Chen, Fang; Atwell, Susana

2017-01-01

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

Quantitative Resistance: More Than Just Perception of a Pathogen.

PubMed

Corwin, Jason A; Kliebenstein, Daniel J

2017-04-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. © 2017 American Society of Plant Biologists. All rights reserved.

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

PubMed

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

2017-11-01

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

Genetic conversion of a fungal plant pathogen to a non-pathogenic, endophytic mutualist

USGS Publications Warehouse

Freeman, Stanley; Rodriguez, Rusty J.

1993-01-01

The filamentous fungal ascomycete Colletotrichum magna causes anthracnose in cucurbit plants. Isolation of a nonpathogenic mutant of this species (path-1) resulted in maintained wild-type levels of in vitro sporulation, spore adhesion, appressorial formation, and infection. Path-1 grew throughout host tissues as an endophyte and retained the wild-type host range, which indicates that the genetics involved in pathogenicity and host specificity are distinct. Prior infection with path-1 protected plants from disease caused by Colletotrichum and Fusarium.Genetic analysis of a cross between path-1 and wild-type strains indicated mutation of a single locus.

Combination of RNAseq and SNP nanofluidic array reveals the center of genetic diversity of cacao pathogen Moniliophthora roreri in the upper Magdalena Valley of Colombia and its clonality

USDA-ARS?s Scientific Manuscript database

Moniliophthora roreri is the fungal pathogen that causes frosty pod rot (FPR) disease of Theobroma cacao L., the source of chocolate. FPR occurs in most of the cacao producing countries in the Western Hemisphere, causing yield losses up to 80%. Genetic diversity within the FPR pathogen population ma...

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing

PubMed Central

Susswein, Lisa R.; Marshall, Megan L.; Nusbaum, Rachel; Vogel Postula, Kristen J.; Weissman, Scott M.; Yackowski, Lauren; Vaccari, Erica M.; Bissonnette, Jeffrey; Booker, Jessica K.; Cremona, M. Laura; Gibellini, Federica; Murphy, Patricia D.; Pineda-Alvarez, Daniel E.; Pollevick, Guido D.; Xu, Zhixiong; Richard, Gabi; Bale, Sherri; Klein, Rachel T.; Hruska, Kathleen S.; Chung, Wendy K.

2016-01-01

Purpose: Germ-line testing for panels of cancer genes using next-generation sequencing is becoming more common in clinical care. We report our experience as a clinical laboratory testing both well-established, high-risk cancer genes (e.g., BRCA1/2, MLH1, MSH2) as well as more recently identified cancer genes (e.g., PALB2, BRIP1), many of which have increased but less well-defined penetrance. Genet Med 18 8, 823–832. Methods: Clinical genetic testing was performed on over 10,000 consecutive cases referred for evaluation of germ-line cancer genes, and results were analyzed for frequency of pathogenic or likely pathogenic variants, and were stratified by testing panel, gene, and clinical history. Genet Med 18 8, 823–832. Results: Overall, a molecular diagnosis was made in 9.0% of patients tested, with the highest yield in the Lynch syndrome/colorectal cancer panel. In patients with breast, ovarian, or colon/stomach cancer, positive yields were 9.7, 13.4, and 14.8%, respectively. Approximately half of the pathogenic variants identified in patients with breast or ovarian cancer were in genes other than BRCA1/2. Genet Med 18 8, 823–832. Conclusion: The high frequency of positive results in a wide range of cancer genes, including those of high penetrance and with clinical care guidelines, underscores both the genetic heterogeneity of hereditary cancer and the usefulness of multigene panels over genetic tests of one or two genes. Genet Med 18 8, 823–832. PMID:26681312

Transfer of plasmid DNA to clinical coagulase-negative staphylococcal pathogens by using a unique bacteriophage.

PubMed

Winstel, Volker; Kühner, Petra; Krismer, Bernhard; Peschel, Andreas; Rohde, Holger

2015-04-01

Genetic manipulation of emerging bacterial pathogens, such as coagulase-negative staphylococci (CoNS), is a major hurdle in clinical and basic microbiological research. Strong genetic barriers, such as restriction modification systems or clustered regularly interspaced short palindromic repeats (CRISPR), usually interfere with available techniques for DNA transformation and therefore complicate manipulation of CoNS or render it impossible. Thus, current knowledge of pathogenicity and virulence determinants of CoNS is very limited. Here, a rapid, efficient, and highly reliable technique is presented to transfer plasmid DNA essential for genetic engineering to important CoNS pathogens from a unique Staphylococcus aureus strain via a specific S. aureus bacteriophage, Φ187. Even strains refractory to electroporation can be transduced by this technique once donor and recipient strains share similar Φ187 receptor properties. As a proof of principle, this technique was used to delete the alternative transcription factor sigma B (SigB) via allelic replacement in nasal and clinical Staphylococcus epidermidis isolates at high efficiencies. The described approach will allow the genetic manipulation of a wide range of CoNS pathogens and might inspire research activities to manipulate other important pathogens in a similar fashion. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains.

PubMed

Argemi, Xavier; Nanoukon, Chimène; Affolabi, Dissou; Keller, Daniel; Hansmann, Yves; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

2018-02-25

Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus ; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8-89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes ( hsrA and dfrG , respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus . Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis .

Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains

PubMed Central

Nanoukon, Chimène; Affolabi, Dissou; Keller, Daniel; Hansmann, Yves; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

2018-01-01

Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8–89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes (hsrA and dfrG, respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus. Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis. PMID:29495323

Genetics: A New Landscape for Medical Geography

PubMed Central

Carrel, Margaret; Emch, Michael

2014-01-01

The emergence and re-emergence of human pathogens resistant to medical treatment will present a challenge to the international public health community in the coming decades. Geography is uniquely positioned to examine the progressive evolution of pathogens across space and through time, and to link molecular change to interactions between population and environmental drivers. Landscape as an organizing principle for the integration of natural and cultural forces has a long history in geography, and, more specifically, in medical geography. Here, we explore the role of landscape in medical geography, the emergent field of landscape genetics, and the great potential that exists in the combination of these two disciplines. We argue that landscape genetics can enhance medical geographic studies of local-level disease environments with quantitative tests of how human-environment interactions influence pathogenic characteristics. In turn, such analyses can expand theories of disease diffusion to the molecular scale and distinguish the important factors in ecologies of disease that drive genetic change of pathogens. PMID:24558292

Functions and origin of plasmids in Erwinia species that are pathogenic to or epiphytically associated with pome fruit trees.

PubMed

Llop, Pablo; Barbé, Silvia; López, María M

The genus Erwinia includes plant-associated pathogenic and non-pathogenic species. Among them, all species pathogenic to pome fruit trees ( E. amylovora, E. pyrifoliae, E. piriflorinigrans, Erwinia sp. from Japan) cause similar symptoms, but differ in their degrees of aggressiveness, i.e. in symptoms, host range or both. The presence of plasmids of similar size, in the range of 30 kb, is a common characteristic that they possess. Besides, they share some genetic content with high homology in several genes associated with exopolysaccharide production and hence, with virulence, as well as in some other genes. Knowledge of the content of these plasmids and comparative genetic analyses may provide interesting new clues to understanding the origin and evolution of these pathogens and the level of symptoms they produce. Furthermore, genetic similarities observed among some of the plasmids (and genomes) from the above indicated pathogenic species and E. tasmaniensis or E. billingiae , which are epiphytic on the same hosts, may reveal associations that could expose the mechanisms of origin of pathogens. A summary of the current information on their plasmids and the relationships among them is presented here.

Reproduction in Leishmania: A focus on genetic exchange.

PubMed

Rougeron, V; De Meeûs, T; Bañuls, A-L

2017-06-01

One key process of the life cycle of pathogens is their mode of reproduction. Indeed, this fundamental biological process conditions the multiplication and the transmission of genes and thus the propagation of diseases in the environment. Reproductive strategies of protozoan parasites have been a subject of debate for many years, principally due to the difficulty in making direct observations of sexual reproduction (i.e. genetic recombination). Traditionally, these parasites were considered as characterized by a preeminent clonal structure. Nevertheless, with the development of elaborate culture experiments, population genetics and evolutionary and population genomics, several studies suggested that most of these pathogens were also characterized by constitutive genetic recombination events. In this opinion, we focused on Leishmania parasites, pathogens responsible of leishmaniases, a major public health issue. We first discuss the evolutionary advantages of a mixed mating reproductive strategy, then we review the evidence of genetic exchange, and finally we detail available tools to detect naturally occurring genetic recombination in Leishmania parasites and more generally in protozoan parasites. Copyright © 2016. Published by Elsevier B.V.

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.

Highly Pathogenic H5N1 Avian Influenza Viruses Exhibit Few Barriers to Gene Flow in Vietnam

PubMed Central

Carrel, Margaret; Wan, Xiu-Feng; Nguyen, Tung; Emch, Michael

2013-01-01

Locating areas where genetic change is inhibited can illuminate underlying processes that drive evolution of pathogens. The persistence of highly pathogenic H5N1 avian influenza in Vietnam since 2003, and the continuous molecular evolution of Vietnamese avian influenza viruses, indicates that local environmental factors are supportive not only of incidence but also of viral adaptation. This article explores whether gene flow is constant across Vietnam, or whether there exist boundary areas where gene flow exhibits discontinuity. Using a dataset of 125 highly pathogenic H5N1 avian influenza viruses, principal components analysis and wombling analysis are used to indicate the location, magnitude, and statistical significance of genetic boundaries. Results show that a small number of geographically minor boundaries to gene flow in highly pathogenic H5N1 avian influenza viruses exist in Vietnam, but that overall there is little division in genetic exchange. This suggests that differences in genetic characteristics of viruses from one region to another are not the result of barriers to H5N1 viral exchange in Vietnam, and that H5N1 avian influenza is able to spread relatively unimpeded across the country. PMID:22350419

Genetic Characterization of Highly Pathogenic Avian Influenza (H5N8) Virus from Domestic Ducks, England, November 2014.

PubMed

Hanna, Amanda; Banks, Jill; Marston, Denise A; Ellis, Richard J; Brookes, Sharon M; Brown, Ian H

2015-05-01

Genetic sequences of a highly pathogenic avian influenza (H5N8) virus in England have high homology to those detected in mainland Europe and Asia during 2014. Genetic characterization suggests this virus is an avian-adapted virus without specific affinity for zoonoses. Spatio-temporal detections of H5N8 imply a role for wild birds in virus spread.

Role of the horizontal gene exchange in evolution of pathogenic Mycobacteria.

PubMed

Reva, Oleg; Korotetskiy, Ilya; Ilin, Aleksandr

2015-01-01

Mycobacterium tuberculosis is one of the most dangerous human pathogens, the causative agent of tuberculosis. While this pathogen is considered as extremely clonal and resistant to horizontal gene exchange, there are many facts supporting the hypothesis that on the early stages of evolution the development of pathogenicity of ancestral Mtb has started with a horizontal acquisition of virulence factors. Episodes of infections caused by non-tuberculosis Mycobacteria reported worldwide may suggest a potential for new pathogens to appear. If so, what is the role of horizontal gene transfer in this process? Availing of accessibility of complete genomes sequences of multiple pathogenic, conditionally pathogenic and saprophytic Mycobacteria, a genome comparative study was performed to investigate the distribution of genomic islands among bacteria and identify ontological links between these mobile elements. It was shown that the ancient genomic islands from M. tuberculosis still may be rooted to the pool of mobile genetic vectors distributed among Mycobacteria. A frequent exchange of genes was observed between M. marinum and several saprophytic and conditionally pathogenic species. Among them M. avium was the most promiscuous species acquiring genetic materials from diverse origins. Recent activation of genetic vectors circulating among Mycobacteria potentially may lead to emergence of new pathogens from environmental and conditionally pathogenic Mycobacteria. The species which require monitoring are M. marinum and M. avium as they eagerly acquire genes from different sources and may become donors of virulence gene cassettes to other micro-organisms.

Tick-Borne Transmission of Two Genetically Distinct Anaplasma marginale Strains following Superinfection of the Mammalian Reservoir Host

USDA-ARS?s Scientific Manuscript database

Strain superinfection affects the dynamics of epidemiological spread of pathogens through a host population. Superinfection has recently been shown to occur for genetically distinct strains of the tick-borne pathogen Anaplasma marginale that encode distinctly different surface protein variants. Supe...

Decay Of Bacterial Pathogens, Fecal Indicators, And Real-Time Quantitative PCR Genetic Markers In Manure-Amended Soils

EPA Science Inventory

This study examined persistence and decay of bacterial pathogens, fecal indicator bacteria (FIB), and emerging real-time quantitative PCR (qPCR) genetic markers for rapid detection of fecal pollution in manure-amended agricultural soils. Known concentrations of transformed green...

Pathogenicity and genetic diversity of Fusarium oxysporum causing soybean root rot in northeast China

USDA-ARS?s Scientific Manuscript database

Soybean is an important edible legume cultivated around the world. However, soybean production is seriously impacted by the widespread occurrence of root rot disease. In this study, genetic diversity and pathogenicity of Fusarium oxysporum associated with root rot of soybean in Heilongjiang province...

Decay Of Bacterial Pathogen, Fecal Indicators, And Real-Time Quantitative PCR Genetic Markers In Manure Amended Soils

EPA Science Inventory

This study examined persistence and decay of bacterial pathogens, fecal indicator bacteria, and emerging real-time quantitative PCR (qPCR) genetic markers for rapid detection of fecal pollution in manre-amended agricultural soils. Known concentrations of transformed green fluore...

Comparative genomics of pathogenic lineages of Vibrio nigripulchritudo identifies virulence-associated traits

PubMed Central

Goudenège, David; Labreuche, Yannick; Krin, Evelyne; Ansquer, Dominique; Mangenot, Sophie; Calteau, Alexandra; Médigue, Claudine; Mazel, Didier; Polz, Martin F; Le Roux, Frédérique

2013-01-01

Vibrio nigripulchritudo is an emerging pathogen of farmed shrimp in New Caledonia and other regions in the Indo-Pacific. The molecular determinants of V. nigripulchritudo pathogenicity are unknown; however, molecular epidemiological studies have suggested that pathogenicity is linked to particular lineages. Here, we performed high-throughput sequencing-based comparative genome analysis of 16 V. nigripulchritudo strains to explore the genomic diversity and evolutionary history of pathogen-containing lineages and to identify pathogen-specific genetic elements. Our phylogenetic analysis revealed three pathogen-containing V. nigripulchritudo clades, including two clades previously identified from New Caledonia and one novel clade comprising putatively pathogenic isolates from septicemic shrimp in Madagascar. The similar genetic distance between the three clades indicates that they have diverged from an ancestral population roughly at the same time and recombination analysis indicates that these genomes have, in the past, shared a common gene pool and exchanged genes. As each contemporary lineage is comprised of nearly identical strains, comparative genomics allowed differentiation of genetic elements specific to shrimp pathogenesis of varying severity. Notably, only a large plasmid present in all highly pathogenic (HP) strains encodes a toxin. Although less/non-pathogenic strains contain related plasmids, these are differentiated by a putative toxin locus. Expression of this gene by a non-pathogenic V. nigripulchritudo strain resulted in production of toxic culture supernatant, normally an exclusive feature of HP strains. Thus, this protein, here termed ‘nigritoxin', is implicated to an extent that remains to be precisely determined in the toxicity of V. nigripulchritudo. PMID:23739050

Genetic Characterization of Highly Pathogenic Avian Influenza (H5N8) Virus from Domestic Ducks, England, November 2014

PubMed Central

Banks, Jill; Marston, Denise A.; Ellis, Richard J.; Brookes, Sharon M.; Brown, Ian H.

2015-01-01

Genetic sequences of a highly pathogenic avian influenza (H5N8) virus in England have high homology to those detected in mainland Europe and Asia during 2014. Genetic characterization suggests this virus is an avian-adapted virus without specific affinity for zoonoses. Spatio-temporal detections of H5N8 imply a role for wild birds in virus spread. PMID:25898126

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

PubMed

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

2012-06-01

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

Marital infidelity and its effect on pathogen diversity

NASA Astrophysics Data System (ADS)

Berryman, Matthew J.

2007-01-01

Marital infidelity is usually examined solely in terms of strategies of men and women, with an emphasis on the enhanced payoff for male infidelity (provided he can get away with it). What are not clear are the strategies used, in terms of how often to engage in extra-marital affairs. It has been proposed that female strategies are governed by a "decision" to maximize the genetic diversity of her offspring, in order to better guarantee that at least some will survive against a common pathogen. This strategy would then impact on the strategies and diversity of pathogens. I make a number of predictions about both strategies and the genetic diversity of humans and pathogens, couched in game-theoretic terms. These predictions are then compared with the existing evidence on the strategies used by women and also in terms of the genetic diversity of human populations.

Purification of high molecular weight genomic DNA from powdery mildew for long-read sequencing

USDA-ARS?s Scientific Manuscript database

The powdery mildew fungi are a group of economically important fungal plant pathogens. Relatively little is known about the molecular biology and genetics of these pathogens, in part due to a lack of well-developed genetic and genomic resources. These organisms have large, repetitive genomes, which ...

Molecular identification, genetic diversity, population genetics and genomics of Rhizoctonia solani. In:perspective of plant pathology in genomic era

USDA-ARS?s Scientific Manuscript database

The basidiomycetous soilborne fungus Rhizoctonia (sensu lato) is an economically important pathogen of worldwide distribution and it is known to attack at least 188 species of higher plants, including agronomic crops, vegetables, ornamentals, forest trees and turfgrasses. The pathogenic isolates may...

Pulmonary arterial hypertension associated to systemic erythematous lupus: molecular characterization of 3 cases.

PubMed

Pousada, Guillermo; Lago-Docampo, Mauro; Baloira, Adolfo; Valverde, Diana

2018-03-08

Pulmonary arterial hypertension associated with systemic lupus erythematosus (PAH-SLE) is a rare disease with a low incidence rate. In this study, PAH related genes and genetic modifiers were characterised molecularly in patients with PAH-SLE. Three patients diagnosed with PAH-SLE and 100 control individuals were analysed after signing an informed consent. Two out of the three analysed patients with PAH-SLE were carriers of pathogenic mutations in the genes BMPR2 and ENG. After an in silico analysis, pathogenic mutations were searched for in control individuals and different databases, with negative results, and they were thus functionally analysed. The third patients only showed polymorphisms in the genes BMPR2, ACVRL1 and ENG. Several genetic variants and genetic modifiers were identified in the three analysed patients. These modifiers, along with the pathogenic mutations, could lead to a more severe clinical course in patients with PAH. We present, for the first time, patients with PAH-SLE carrying pathogenic mutations in the main genes related to PAH and alterations in the genetic modifiers. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.

PubMed

Lee, Cha Gon; Lee, Jeehun; Lee, Munhyang

2018-01-01

Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.

Evolution of eukaryotic microbial pathogens via covert sexual reproduction

PubMed Central

Heitman, Joseph

2010-01-01

Sexual reproduction enables eukaryotic organisms to re-assort genetic diversity and purge deleterious mutations, producing better-fit progeny. Sex arose early and pervades eukaryotes. Fungal and parasite pathogens once thought asexual have maintained cryptic sexual cycles, including unisexual or parasexual reproduction. As pathogens become niche and host-adapted, sex appears to specialize to promote inbreeding and clonality yet maintain out-crossing potential. During self-fertile sexual modes, sex itself may generate genetic diversity de novo. Mating-type loci govern fungal sexual identity; how parasites establish sexual identity is unknown. Comparing and contrasting fungal and parasite sex promises to reveal how microbial pathogens evolved and are evolving. PMID:20638645

The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics

PubMed Central

Corwin, Jason A.; Copeland, Daniel; Feusier, Julie; Subedy, Anushriya; Eshbaugh, Robert; Palmer, Christine; Maloof, Julin; Kliebenstein, Daniel J.

2016-01-01

The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes. PMID:26866607

Genetic evolution of H5 highly pathogenic avian influenza virus in domestic poultry in Vietnam between 2011 and 2013.

PubMed

Lee, Eun-Kyoung; Kang, Hyun-Mi; Kim, Kwang-Il; Choi, Jun-Gu; To, Thanh Long; Nguyen, Tho Dang; Song, Byung-Min; Jeong, Jipseol; Choi, Kang-Seuk; Kim, Ji-Ye; Lee, Hee-Soo; Lee, Youn-Jeong; Kim, Jae-Hong

2015-04-01

In spite of highly pathogenic avian influenza H5N1 vaccination campaigns for domestic poultry, H5N1 viruses continue to circulate in Vietnam. To estimate the prevalence of avian influenza virus in Vietnam, surveillance was conducted between November 2011 and February 2013. Genetic analysis of 312 highly pathogenic avian influenza H5 viruses isolated from poultry in Vietnam was conducted and possible genetic relationships with strains from neighboring countries were investigated. As previously reported, phylogenetic analysis of the avian influenza virus revealed two H5N1 HPAI clades that were circulating in Vietnam. Clade 1.1, related to Cambodian strains, was predominant in the southern provinces, while clade 2.3.2.1 viruses were predominant in the northern and central provinces. Sequence analysis revealed evidence of active genetic evolution. In the gene constellation of clade 2.3.2.1, genotypes A, B, and B(II) existed during the 2011/2012 winter season. In June 2012, new genotype C emerged by reassortment between genotype A and genotype B(II), and this genotype was predominant in 2013 in the northern and central provinces. Interestingly, enzootic Vietnamese clade 2.3.2.1C H5 virus subsequently reassorted with N2, which originated from wild birds, to generate H5N2 highly pathogenic avian influenza, which was isolated from duck in the northeast region. This investigation indicated that H5N1 outbreaks persist in Vietnam and cause genetic reassortment with circulating viruses. It is necessary to strengthen active influenza surveillance to eradicate highly pathogenic avian influenza viruses and sever the link between highly pathogenic avian influenza and other circulating influenza viruses. © 2015 Poultry Science Association Inc.

The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics.

PubMed

Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Subedy, Anushriya; Eshbaugh, Robert; Palmer, Christine; Maloof, Julin; Kliebenstein, Daniel J

2016-02-01

The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes.

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

The Complex Contributions of Genetics and Nutrition to Immunity in Drosophila melanogaster

PubMed Central

Unckless, Robert L.; Rottschaefer, Susan M.; Lazzaro, Brian P.

2015-01-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and “nutritional immunology” has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional “immune system” that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment. PMID:25764027

The complex contributions of genetics and nutrition to immunity in Drosophila melanogaster.

PubMed

Unckless, Robert L; Rottschaefer, Susan M; Lazzaro, Brian P

2015-03-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.

Unveiling common responses of Medicago truncatula to appropriate and inappropriate rust species

PubMed Central

Vaz Patto, Maria Carlota; Rubiales, Diego

2014-01-01

Little is known about the nature of effective defense mechanisms in legumes to pathogens of remotely related plant species. Some rust species are among pathogens with broad host range causing dramatic losses in various crop plants. To understand and compare the different host and nonhost resistance (NHR) responses of legume species against rusts, we characterized the reaction of the model legume Medicago truncatula to one appropriate (Uromyces striatus) and two inappropriate (U. viciae-fabae and U. lupinicolus) rusts. We found that similar pre and post-haustorial mechanisms of resistance appear to be operative in M. truncatula against appropriate and inappropriate rust fungus. The appropriate U. striatus germinated better on M. truncatula accessions then the inappropriate U. viciae-fabae and U. lupinicolus, but once germinated, germ tubes of the three rusts had a similar level of success in finding stomata and forming an appressoria over a stoma. However, responses to different inappropriate rust species also showed some specificity, suggesting a combination of non-specific and specific responses underlying this legume NHR to rust fungi. Further genetic and expression analysis studies will contribute to the development of the necessary molecular tools to use the present information on host and NHR mechanisms to breed for broad-spectrum resistance to rust in legume species. PMID:25426128

Development of Decision Support System for Remote Monitoring of PIP Corn

EPA Science Inventory

The EPA is developing a multi-level approach that utilizes satellite and airborne remote sensing to locate and monitor genetically modified corn in the agricultural landscape and pest infestation. The current status of the EPA IRM monitoring program based on remote sensed imager...

Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

PubMed

Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

2015-04-01

Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

[Algorithm of toxigenic genetically altered Vibrio cholerae El Tor biovar strain identification].

PubMed

Smirnova, N I; Agafonov, D A; Zadnova, S P; Cherkasov, A V; Kutyrev, V V

2014-01-01

Development of an algorithm of genetically altered Vibrio cholerae biovar El Tor strai identification that ensures determination of serogroup, serovar and biovar of the studied isolate based on pheno- and genotypic properties, detection of genetically altered cholera El Tor causative agents, their differentiation by epidemic potential as well as evaluation of variability of key pathogenicity genes. Complex analysis of 28 natural V. cholerae strains was carried out by using traditional microbiological methods, PCR and fragmentary sequencing. An algorithm of toxigenic genetically altered V. cholerae biovar El Tor strain identification was developed that includes 4 stages: determination of serogroup, serovar and biovar based on phenotypic properties, confirmation of serogroup and biovar based on molecular-genetic properties determination of strains as genetically altered, differentiation of genetically altered strains by their epidemic potential and detection of ctxB and tcpA key pathogenicity gene polymorphism. The algorithm is based on the use of traditional microbiological methods, PCR and sequencing of gene fragments. The use of the developed algorithm will increase the effectiveness of detection of genetically altered variants of the cholera El Tor causative agent, their differentiation by epidemic potential and will ensure establishment of polymorphism of genes that code key pathogenicity factors for determination of origins of the strains and possible routes of introduction of the infection.

The Xylella fastidosa RTX operons: evidence for the evolution of protein mosaics through novel genetic exchanges.

PubMed

Gambetta, Gregory A; Matthews, Mark A; Syvanen, Michael

2018-05-04

Xylella fastidiosa (Xf) is a gram negative bacterium inhabiting the plant vascular system. In most species this bacterium lives as a benign symbiote, but in several agriculturally important plants (e.g. coffee, citrus, grapevine) Xf is pathogenic. Xf has four loci encoding homologues to hemolysin RTX proteins, virulence factors involved in a wide range of plant pathogen interactions. We show that all four genes are expressed during pathogenesis in grapevine. The sequences from these four genes have a complex repetitive structure. At the C-termini, sequence diversity between strains is what would be expected from orthologous genes. However, within strains there is no N-terminal homology, indicating these loci encode RTXs of different functions and/or specificities. More striking is that many of the orthologous loci between strains share this extreme variation at the N-termini. Thus these RTX orthologues are most easily visualized as fusions between the orthologous C-termini and different N-termini. Further, the four genes are found in operons having a peculiar structure with an extensively duplicated module encoding a small protein with homology to the N-terminal region of the full length RTX. Surprisingly, some of these small peptides are most similar not to their corresponding full length RTX, but to the N-termini of RTXs from other Xf strains, and even other remotely related species. These results demonstrate that these genes are expressed in planta during pathogenesis. Their structure suggests extensive evolutionary restructuring through horizontal gene transfers and heterologous recombination mechanisms. The sum of the evidence suggests these repetitive modules are a novel kind of mobile genetic element.

Burkholderia thailandensis: Genetic Manipulation.

PubMed

Garcia, Erin C

2017-05-16

Burkholderia thailandensis is a Gram-negative bacterium endemic to Southeast Asian and northern Australian soils. It is non-pathogenic; therefore, it is commonly used as a model organism for the related human pathogens Burkholderia mallei and Burkholderia pseudomallei. B. thailandensis is relatively easily genetically manipulated and a variety of robust genetic tools can be used in this organism. This unit describes protocols for conjugation, natural transformation, mini-Tn7 insertion, and allelic exchange in B. thailandensis. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Ecological genetics of the Bromus tectorum (Poaceae) - Ustilago Bullata (Ustilaginaceae): A role for frequency dependent selection?

Treesearch

Susan E. Meyer; David L. Nelson; Suzette Clement; Alisa Ramakrishnan

2010-01-01

Evolutionary processes that maintain genetic diversity in plants are likely to include selection imposed by pathogens. Negative frequency-dependent selection is a mechanism for maintenance of resistance polymorphism in plant - pathogen interactions. We explored whether such selection operates in the Bromus tectorum - Ustilago bullata pathosystem. Gene-for-gene...

Population genetic structure of Venturia effusa, cause of pecan scab, in the southeastern United States

USDA-ARS?s Scientific Manuscript database

Venturia effusa is the most important pathogen of pecan in the southeastern USA. Little information exists on the population biology and genetic diversity of the pathogen. A hierarchical sampling of a total of 784 isolates from 63 trees in 11 pecan orchards in the southeastern USA were screened agai...

Phytophthora ramorum and sudden oak death in California: III. preliminary studies in pathogen genetics

Treesearch

Matteo Garbelotto; David M. Rizzo; Katie Hayden; Monica Meija-Chang; Jennifer M. Davidson; Steven Tjosvold

2002-01-01

Sudden oak death (SOD) has been shown to be caused by a new species of Phytophthora, P. ramorum. A basic understanding of the genetics of P. ramorum is critical to any management strategy. We have initiated a number of studies to examine species concepts, population biology and mating behavior of the pathogen....

Highly pathogenic avian influenza A(H7N9) virus, Tennessee, USA, March 2017

USDA-ARS?s Scientific Manuscript database

In March 2017, highly pathogenic avian influenza A(H7N9) was detected at 2 poultry farms in Tennessee, USA. Surveillance data and genetic analyses indicated multiple introductions of low pathogenicity avian influenza virus before mutation to high pathogenicity and interfarm transmission. Poultry sur...

Anaplasma marginale superinfection attributable to pathogen strains with distinct genomic backgrounds.

USDA-ARS?s Scientific Manuscript database

Microbial strain structure is dynamic over space and time; shifts in pathogen strain structure result in changing patterns of disease. The scale of change in space and time differs markedly among pathogens depending on multiple factors including pathogen-specific mechanisms of genetic change and the...

Known genetic susceptibility factors for chronic pancreatitis in patients of European ancestry are rare in patients of African ancestry.

PubMed

Phillips, Anna Evans; LaRusch, Jessica; Greer, Phil; Abberbock, Judah; Alkaade, Samer; Amann, Stephen T; Anderson, Michelle A; Baillie, John; Banks, Peter A; Brand, Randall E; Conwell, Darwin; Coté, Gregory A; Forsmark, Christopher E; Gardner, Timothy B; Gelrud, Andres; Guda, Nalini; Lewis, Michele; Money, Mary E; Muniraj, Thiruvengadam; Sandhu, Bimaljit S; Sherman, Stuart; Singh, Vikesh K; Slivka, Adam; Tang, Gong; Wilcox, C Mel; Whitcomb, David C; Yadav, Dhiraj

2018-05-19

Multiple pathogenic genetic variants are associated with pancreatitis in patients of European (EA) and Asian ancestries, but studies on patients of African ancestry (AA) are lacking. We evaluated the prevalence of known genetic variations in African-American subjects in the US. We studied prospectively enrolled controls (n = 238) and patients with chronic (CP) (n = 232) or recurrent acute pancreatitis (RAP) (n = 45) in the NAPS2 studies from 2000-2014 of self-identified AA. Demographic and phenotypic information was obtained from structured questionnaires. Ancestry and admixture were evaluated by principal component analysis (PCA). Genotyping was performed for pathogenic genetic variants in PRSS1, SPINK1, CFTR and CTRC. Prevalence of disease-associated variants in NAPS2 subjects of AA and EA was compared. When compared with CP subjects of EA (n = 862), prevalence of established pathogenic genetic variants was infrequent in AA patients with CP, overall (29 vs. 8.19%, OR 4.60, 95% CI 2.74-7.74, p < 0.001), and after stratification by alcohol etiology (p < 0.001). On PCA, AA cases were more heterogeneous but distinct from EA subjects; no difference was observed between AA subjects with and without CP-associated variants. Of 19 A A patients with CP who had pathogenic genetic variants, 2 had variants in PRSS1 (R122H, R122C), 4 in SPINK1 (all N34S heterozygotes), 12 in CFTR (2 CFTR sev , 9 CFTR BD , 1 compound heterozygote with CFTR sev and CFTR BD ), and 1 in CTRC (R254W). Pathogenic genetic variants reported in EA patients are significantly less common in AA patients. Further studies are needed to determine the complex risk factors for AA subjects with pancreatitis. Copyright © 2018. Published by Elsevier B.V.

Threats, status & management options for bristlecone pines and limber pines in Southern Rockies

Treesearch

A. W. Schoettle; K. S. Burns; F. Freeman; R. A. Sniezko

2006-01-01

High-elevation white pines define the most remote alpine-forest ecotones in western North America yet they are not beyond the reach of a lethal non-native pathogen. The pathogen (Cronartium ribicola), a native to Asia, causes the disease white pine blister rust (WPBR) and was introduced into western Canada in 1910. Whitebark (Pinus albicaulis) and...

Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses

PubMed Central

Wang, Zheng; Malanoski, Anthony P; Lin, Baochuan; Kidd, Carolyn; Long, Nina C; Blaney, Kate M; Thach, Dzung C; Tibbetts, Clark; Stenger, David A

2008-01-01

Background Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. Results Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. Conclusion This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses. PMID:19046445

Genetic Counseling

MedlinePlus

... Testing Evaluating Genomic Tests Epidemiology Pathogen Genomics Resources Genetic Counseling Recommend on Facebook Tweet Share Compartir In ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

Local adaptation and evolutionary potential along a temperature gradient in the fungal pathogen Rhynchosporium commune

PubMed Central

Stefansson, Tryggvi S; McDonald, Bruce A; Willi, Yvonne

2013-01-01

To predict the response of plant pathogens to climate warming, data are needed on current thermal adaptation, the pathogen's evolutionary potential, and the link between them. We conducted a common garden experiment using isolates of the fungal pathogen Rhynchosporium commune from nine barley populations representing climatically diverse locations. Clonal replicates of 126 genetically distinct isolates were assessed for their growth rate at 12°C, 18°C, and 22°C. Populations originating from climates with higher monthly temperature variation had higher growth rate at all three temperatures compared with populations from climates with less temperature fluctuation. Population differentiation in growth rate (QST) was significantly higher at 22°C than population differentiation for neutral microsatellite loci (GST), consistent with local adaptation for growth at higher temperatures. At 18°C, we found evidence for stabilizing selection for growth rate as QST was significantly lower than GST. Heritability of growth rate under the three temperatures was substantial in all populations (0.58–0.76). Genetic variation was lower in populations with higher growth rate at the three temperatures and evolvability increased under heat stress in seven of nine populations. Our findings imply that the distribution of this pathogen is unlikely to be genetically limited under climate warming, due to its high genetic variation and plasticity for thermal tolerance. PMID:23745143

Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic heterogeneity within a Legionnaires' disease outbreak.

PubMed

McAdam, Paul R; Vander Broek, Charles W; Lindsay, Diane S J; Ward, Melissa J; Hanson, Mary F; Gillies, Michael; Watson, Mick; Stevens, Joanne M; Edwards, Giles F; Fitzgerald, J Ross

2014-01-01

Legionnaires' disease is a severe form of pneumonia caused by the environmental bacterium Legionella pneumophila. Outbreaks commonly affect people with known risk factors, but the genetic and pathogenic complexity of L. pneumophila within an outbreak is not well understood. Here, we investigate the etiology of the major Legionnaires' disease outbreak that occurred in Edinburgh, UK, in 2012, by examining the evolutionary history, genome content, and virulence of L. pneumophila clinical isolates. Our high resolution genomic approach reveals that the outbreak was caused by multiple genetic subtypes of L. pneumophila, the majority of which had diversified from a single progenitor through mutation, recombination, and horizontal gene transfer within an environmental reservoir prior to release. In addition, we discover that some patients were infected with multiple L. pneumophila subtypes, a finding which can affect the certainty of source attribution. Importantly, variation in the complement of type IV secretion systems encoded by different genetic subtypes correlates with virulence in a Galleria mellonella model of infection, revealing variation in pathogenic potential among the outbreak source population of L. pneumophila. Taken together, our study indicates previously cryptic levels of pathogen heterogeneity within a Legionnaires' disease outbreak, a discovery that impacts on source attribution for future outbreak investigations. Furthermore, our data suggest that in addition to host immune status, pathogen diversity may be an important influence on the clinical outcome of individual outbreak infections.

Method for genetic identification of unknown organisms

DOEpatents

Colston, Jr., Billy W.; Fitch, Joseph P.; Hindson, Benjamin J.; Carter, Chance J.; Beer, Neil Reginald

2016-08-23

A method of rapid, genome and proteome based identification of unknown pathogenic or non-pathogenic organisms in a complex sample. The entire sample is analyzed by creating millions of emulsion encapsulated microdroplets, each containing a single pathogenic or non-pathogenic organism sized particle and appropriate reagents for amplification. Following amplification, the amplified product is analyzed.

Resequencing of the Phytophthora ramorum genome to characterize genetic variation and population dynamics of the invasive pathogen

Treesearch

Jennifer Yuzon; David M. Rizzo; Mathu Malar C; Sucheta Tripathy; Takao Kasuga

2017-01-01

Phytophthora ramorum has spread and diversified throughout California’s northwestern coast since its introduction in the 1990s. Tracking the spread of P. ramorum and the functional response of the pathogen to the environment is of particular interest to managing the epidemic. Using genetic tools such as microsatellite...

Population genetic structure of the seed pathogen Pyrenophora semeniperda on Bromus tectorum in western North America

Treesearch

David Boose; Steven Harrison; Suzette Clement; Susan E. Meyer

2011-01-01

We examined genetic variation in the ascomycete pathogen Pyrenophora semeniperda cultured from seeds of the invasive grass Bromus tectorum in the Intermountain West of North America. We sequenced the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA genome in 417 monoconidial cultures collected from 20 sites in Washington, Idaho, Utah and Colorado,...

Pathogen-driven selection in the human genome.

PubMed

Cagliani, Rachele; Sironi, Manuela

2013-01-01

Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infections are estimated to account for about 15% of deaths. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity. Indeed, recent evidences indicated that among the diverse environmental factors that acted as selective pressures during the evolution of our species, pathogen load had the strongest influence. Beside the textbook example of the major histocompatibility complex, selection signatures left by pathogen-exerted pressure can be identified at several human loci, including genes not directly involved in immune response. In the future, high-throughput technologies and the availability of genetic data from different populations are likely to provide novel insights into the evolutionary relationships between the human host and its pathogens. Hopefully, this will help identify the genetic determinants modulating the susceptibility to infectious diseases and will translate into new treatment strategies.

Horizontal Gene Acquisitions, Mobile Element Proliferation, and Genome Decay in the Host-Restricted Plant Pathogen Erwinia Tracheiphila

PubMed Central

Shapiro, Lori R.; Scully, Erin D.; Straub, Timothy J.; Park, Jihye; Stephenson, Andrew G.; Beattie, Gwyn A.; Gleason, Mark L.; Kolter, Roberto; Coelho, Miguel C.; De Moraes, Consuelo M.; Mescher, Mark C.; Zhaxybayeva, Olga

2016-01-01

Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen Erwinia tracheiphila (Enterobacteriaceae) isolated from infected squash plants in New York, Pennsylvania, Kentucky, and Michigan. These genomes exhibit a high proportion of recent horizontal gene acquisitions, invasion and remarkable amplification of mobile genetic elements, and pseudogenization of approximately 20% of the coding sequences. These genome attributes indicate that E. tracheiphila recently emerged as a host-restricted pathogen. Furthermore, chromosomal rearrangements associated with phage and transposable element proliferation contribute to substantial differences in gene content and genetic architecture between the six E. tracheiphila strains and other Erwinia species. Together, these data lead us to hypothesize that E. tracheiphila has undergone recent evolution through both genome decay (pseudogenization) and genome expansion (horizontal gene transfer and mobile element amplification). Despite evidence of dramatic genomic changes, the six strains are genetically monomorphic, suggesting a recent population bottleneck and emergence into E. tracheiphila’s current ecological niche. PMID:26992913

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity.

PubMed

Copin, Richard; Wang, Xueying; Louie, Eddie; Escuyer, Vincent; Coscolla, Mireia; Gagneux, Sebastien; Palmer, Guy H; Ernst, Joel D

2016-12-01

Molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. Mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. Here, we compared the genetic diversity of the bacteria that established infection to the bacterial populations obtained from infected tissues during murine M. tuberculosis pulmonary infection and human disseminated M. bovis BCG infection. We found that new mutations accumulate during in vitro culture, but that in vivo, purifying selection against new mutations dominates, indicating that M. tuberculosis follows a dominant lineage model of evolution. Comparing bacterial populations passaged in T cell-deficient and immunocompetent mice, we found that the presence of T cells is associated with an increase in the diversity of the M. tuberculosis genome. Together, our findings put M. tuberculosis genetic evolution in a new perspective and clarify the impact of T cells on sequence diversity of M. tuberculosis.

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.

Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

PubMed Central

Elmer, Jacob J.; Christensen, Matthew D.; Rege, Kaushal

2014-01-01

Horizontal gene transfer (HGT) is widespread amongst prokaryotes, but eukaryotes tend to be far less promiscuous with their genetic information. However, several examples of HGT from pathogens into eukaryotic cells have been discovered and mimicked to improve non-viral gene delivery techniques. For example, several viral proteins and DNA sequences have been used to significantly increase cytoplasmic and nuclear gene delivery. Plant genetic engineering is routinely performed with the pathogenic bacterium Agrobacterium tumefaciens and similar pathogens (e.g. Bartonella henselae) may also be able to transform human cells. Intracellular parasites like Trypanosoma cruzi may also provide new insights into overcoming cellular barriers to gene delivery. Finally, intercellular nucleic acid transfer between host cells will also be briefly discussed. This article will review the unique characteristics of several different viruses and microbes and discuss how their traits have been successfully applied to improve non-viral gene delivery techniques. Consequently, pathogenic traits that originally caused diseases may eventually be used to treat many genetic diseases. PMID:23994344

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...

Human susceptibility to legionnaires' disease.

PubMed

Berrington, William R; Hawn, Thomas R

2013-01-01

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

Genetic of virulence in Ascochyta rabiei

USDA-ARS?s Scientific Manuscript database

Many attempts have been made to classify variation in virulence of the chickpea Ascochyta blight pathogen, Ascochyta rabiei, into discrete categories referred to as “pathogenic groups”, “races” or “pathotypes”. Results have been inconsistent and conflicting due to differences in host and pathogen...

pH Dependency of sclerotial development and pathogenicity revealed by using genetically defined oxalate-minus mutants of Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

The devastating plant pathogen Sclerotinia sclerotiorum produces copious (up to 50mM) amounts of oxalic acid, which, for over a quarter century, has been claimed as the pathogenicity determinant based on UV-induced mutants that concomitantly lost oxalate production and pathogenicity. Such a claim wa...

Identification of eighteen Berberis species as alternate hosts of Puccinia striiformis f. sp. tritici and virulence variation in the pathogen isolates from natural infection of barberry plants in China

USDA-ARS?s Scientific Manuscript database

The wheat stripe rust pathogen (Puccinia striiformis f. sp. tritici, Pst) population in China has been reported to be a distinct genetic group with higher diversity than those in many other countries. Genetic recombination in the Pst population has been identified with molecular markers, but whethe...

Altered distribution of susceptibility phenotypes implies environmental modulation of genetic resistance

Treesearch

Thomas R. Gordon; Neil McRoberts

2012-01-01

Resistance to disease is determined by the genetic capacity of a plant to recognize and respond to a pathogen, as modified to varying degrees by the environment in which the interaction occurs. Physical factors such as temperature and moisture can limit the ability of a pathogen to infect and cause disease, and may also influence the response of the host through...

Molecular genetic characterization of the koa-wilt pathogen (Fusarium oxysporum): Application of molecular genetic tools toward improving koa restoration in Hawai'i

Treesearch

Mee-Sook Kim; Jane E. Stewart; Nicklos Dudley; John Dobbs; Tyler Jones; Phil G. Cannon; Robert L. James; Kas Dumroese; Ned B. Klopfenstein

2015-01-01

Several forest diseases are causing serious threats to the native Hawaiian forest. Among them, koawilt disease (caused by Fusarium oxysporum) is damaging to native populations of koa (Acacia koa), and it also hinders koa restoration/reforestation. Because F. oxysporum likely represents a complex of species with distinct pathogenic activities, more detailed...

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

The genetic basis of local adaptation for pathogenic fungi in agricultural ecosystems.

PubMed

Croll, Daniel; McDonald, Bruce A

2017-04-01

Local adaptation plays a key role in the evolutionary trajectory of host-pathogen interactions. However, the genetic architecture of local adaptation in host-pathogen systems is poorly understood. Fungal plant pathogens in agricultural ecosystems provide highly tractable models to quantify phenotypes and map traits to corresponding genomic loci. The outcome of crop-pathogen interactions is thought to be governed largely by gene-for-gene interactions. However, recent studies showed that virulence can be governed by quantitative trait loci and that many abiotic factors contribute to the outcome of the interaction. After introducing concepts of local adaptation and presenting examples from wild plant pathosystems, we focus this review on a major pathogen of wheat, Zymoseptoria tritici, to show how a multitude of traits can affect local adaptation. Zymoseptoria tritici adapted to different thermal environments across its distribution range, indicating that thermal adaptation may limit effective dispersal to different climates. The application of fungicides led to the rapid evolution of multiple, independent resistant populations. The degree of colony melanization showed strong pleiotropic effects with other traits, including trade-offs with colony growth rates and fungicide sensitivity. The success of the pathogen on its host can be assessed quantitatively by counting pathogen reproductive structures and measuring host damage based on necrotic lesions. Interestingly, these two traits can be weakly correlated and depend both on host and pathogen genotypes. Quantitative trait mapping studies showed that the genetic architecture of locally adapted traits varies from single loci with large effects to many loci with small individual effects. We discuss how local adaptation could hinder or accelerate the development of epidemics in agricultural ecosystems. © 2016 John Wiley & Sons Ltd.

Genetic adaptation to historical pathogen burdens.

PubMed

Fedderke, Johannes W; Klitgaard, Robert E; Napolioni, Valerio

2017-10-01

Historical pathogen burdens are examined as possible triggers for genetic adaptation. Evidence of adaptation emerges for the acid phosphatase locus 1 (ACP1), interleukin-6 (IL6), interleukin-10 (IL10 ), human leukocyte antigen (HLA) polymorphisms, along with a measure of heterozygosity over 783 alleles. Results are robust to controlling for the physical and historical environment humans faced, and to endogeneity of the historical pathogen burden measure. The present study represents a proof-of-concept which may pave the way to the analysis of future aggregate measures coming from whole-genome sequencing/genotyping data. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic variation underlying resistance to infectious hematopoietic necrosis virus in a steelhead trout (Oncorhynchus mykiss) population

USGS Publications Warehouse

Brieuc, Marine S. O.; Purcell, Maureen K.; Palmer, Alexander D.; Naish, Kerry A.

2015-01-01

Understanding the mechanisms of host resistance to pathogens will allow insights into the response of wild populations to the emergence of new pathogens. Infectious hematopoietic necrosis virus (IHNV) is endemic to the Pacific Northwest and infectious to Pacific salmon and trout (Oncorhynchus spp.). Emergence of the M genogroup of IHNV in steelhead trout O. mykiss in the coastal streams of Washington State, between 2007 and 2011, was geographically heterogeneous. Differences in host resistance due to genetic change were hypothesized to be a factor influencing the IHNV emergence patterns. For example, juvenile steelhead trout losses at the Quinault National Fish Hatchery (QNFH) were much lower than those at a nearby facility that cultures a stock originally derived from the same source population. Using a classical quantitative genetic approach, we determined the potential for the QNFH steelhead trout population to respond to selection caused by the pathogen, by estimating the heritability for 2 traits indicative of IHNV resistance, mortality (h2 = 0.377 (0.226 - 0.550)) and days to death (h2 = 0.093 (0.018 - 0.203)). These results confirm that there is a genetic basis for resistance and that this population has the potential to adapt to IHNV. Additionally, genetic correlation between days to death and fish length suggests a correlated response in these traits to selection. Reduction of genetic variation, as well as the presence or absence of resistant alleles, could affect the ability of populations to adapt to the pathogen. Identification of the genetic basis for IHNV resistance could allow the assessment of the susceptibility of other steelhead populations.

Molecular Epidemiology of Novel Pathogen "Brachyspira hampsonii" Reveals Relationships between Diverse Genetic Groups, Regions, Host Species, and Other Pathogenic and Commensal Brachyspira Species.

PubMed

Mirajkar, Nandita S; Bekele, Aschalew Z; Chander, Yogesh Y; Gebhart, Connie J

2015-09-01

Outbreaks of bloody diarrhea in swine herds in the late 2000s signaled the reemergence of an economically significant disease, swine dysentery, in the United States. Investigations confirmed the emergence of a novel spirochete in swine, provisionally designated "Brachyspira hampsonii," with two genetically distinct clades. Although it has since been detected in swine and migratory birds in Europe and North America, little is known about its genetic diversity or its relationships with other Brachyspira species. This study characterizes B. hampsonii using a newly developed multilocus sequence typing (MLST) approach and elucidates the diversity, distribution, population structure, and genetic relationships of this pathogen from diverse epidemiological sources globally. Genetic characterization of 81 B. hampsonii isolates, originating from six countries, with our newly established MLST scheme identified a total of 20 sequence types (STs) belonging to three clonal complexes (CCs). B. hampsonii showed a heterogeneous population structure with evidence of microevolution locally in swine production systems, while its clustering patterns showed associations with its epidemiological origins (country, swine production system, and host species). The close genetic relatedness of B. hampsonii isolates from different countries and host species highlights the importance of strict biosecurity control measures. A comparative analysis of 430 isolates representing seven Brachyspira species (pathogens and commensals) from 19 countries and 10 host species depicted clustering by microbial species. It revealed the close genetic relatedness of B. hampsonii with commensal Brachyspira species and also provided support for the two clades of B. hampsonii to be considered a single species. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genetic diversity in Treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

PubMed Central

Šmajs, David; Norris, Steven J.; Weinstock, George M.

2013-01-01

Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, T. paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections. PMID:22198325

Genetic diversity predicts pathogen resistance and cell-mediated immunocompetence in house finches

PubMed Central

Hawley, Dana M; Sydenstricker, Keila V; Kollias, George V; Dhondt, André A

2005-01-01

Evidence is accumulating that genetic variation within individual hosts can influence their susceptibility to pathogens. However, there have been few opportunities to experimentally test this relationship, particularly within outbred populations of non-domestic vertebrates. We performed a standardized pathogen challenge in house finches (Carpodacus mexicanus) to test whether multilocus heterozygosity across 12 microsatellite loci predicts resistance to a recently emerged strain of the bacterial pathogen, Mycoplasma gallisepticum (MG). We simultaneously tested whether the relationship between heterozygosity and pathogen susceptibility is mediated by differences in cell-mediated or humoral immunocompetence. We inoculated 40 house finches with MG under identical conditions and assayed both humoral and cell-mediated components of the immune response. Heterozygous house finches developed less severe disease when infected with MG, and they mounted stronger cell-mediated immune responses to phytohaemagglutinin. Differences in cell-mediated immunocompetence may, therefore, partly explain why more heterozygous house finches show greater resistance to MG. Overall, our results underscore the importance of multilocus heterozygosity for individual pathogen resistance and immunity. PMID:17148199

Genetic variation in transmission success of the Lyme borreliosis pathogen Borrelia afzelii.

PubMed

Tonetti, Nicolas; Voordouw, Maarten J; Durand, Jonas; Monnier, Séverine; Gern, Lise

2015-04-01

The vector-to-host and host-to-vector transmission steps are the two critical events that define the life cycle of any vector-borne pathogen. We expect negative genetic correlations between these two transmission phenotypes, if parasite genotypes specialized at invading the vector are less effective at infecting the vertebrate host and vice versa. We used the tick-borne bacterium Borrelia afzelii, a causative agent of Lyme borreliosis in Europe, to test whether genetic trade-offs exist between tick-to-host, systemic (host-to-tick), and a third mode of co-feeding (tick-to-tick) transmission. We worked with six strains of B. afzelii that were differentiated according to their ospC gene. We compared the three components of transmission among the B. afzelii strains using laboratory rodents as the vertebrate host and a laboratory colony of Ixodes ricinus as the tick vector. We used next generation matrix models to combine these transmission components into a single estimate of the reproductive number (R0) for each B. afzelii strain. We also tested whether these strain-specific estimates of R0 were correlated with the strain-specific frequencies in the field. We found significant genetic variation in the three transmission components among the B. afzelii strains. This is the first study to document genetic variation in co-feeding transmission for any tick-borne pathogen. We found no evidence of trade-offs as the three pairwise correlations of the transmission rates were all positive. The R0 values from our laboratory study explained 45% of the variation in the frequencies of the B. afzelii ospC strains in the field. Our study suggests that laboratory estimates of pathogen fitness can predict the distribution of pathogen strains in nature. Copyright © 2015 Elsevier GmbH. All rights reserved.

[Genetic diagnostics of pathogenic splicing abnormalities in the clinical laboratory--pitfalls and screening approaches].

PubMed

Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao

2010-12-01

In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.

A Systematic Bayesian Integration of Epidemiological and Genetic Data

PubMed Central

Lau, Max S. Y.; Marion, Glenn; Streftaris, George; Gibson, Gavin

2015-01-01

Genetic sequence data on pathogens have great potential to inform inference of their transmission dynamics ultimately leading to better disease control. Where genetic change and disease transmission occur on comparable timescales additional information can be inferred via the joint analysis of such genetic sequence data and epidemiological observations based on clinical symptoms and diagnostic tests. Although recently introduced approaches represent substantial progress, for computational reasons they approximate genuine joint inference of disease dynamics and genetic change in the pathogen population, capturing partially the joint epidemiological-evolutionary dynamics. Improved methods are needed to fully integrate such genetic data with epidemiological observations, for achieving a more robust inference of the transmission tree and other key epidemiological parameters such as latent periods. Here, building on current literature, a novel Bayesian framework is proposed that infers simultaneously and explicitly the transmission tree and unobserved transmitted pathogen sequences. Our framework facilitates the use of realistic likelihood functions and enables systematic and genuine joint inference of the epidemiological-evolutionary process from partially observed outbreaks. Using simulated data it is shown that this approach is able to infer accurately joint epidemiological-evolutionary dynamics, even when pathogen sequences and epidemiological data are incomplete, and when sequences are available for only a fraction of exposures. These results also characterise and quantify the value of incomplete and partial sequence data, which has important implications for sampling design, and demonstrate the abilities of the introduced method to identify multiple clusters within an outbreak. The framework is used to analyse an outbreak of foot-and-mouth disease in the UK, enhancing current understanding of its transmission dynamics and evolutionary process. PMID:26599399

Sexual Reproduction of Human Fungal Pathogens

PubMed Central

Heitman, Joseph; Carter, Dee A.; Dyer, Paul S.; Soll, David R.

2014-01-01

We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms. PMID:25085958

mirVAFC: A Web Server for Prioritizations of Pathogenic Sequence Variants from Exome Sequencing Data via Classifications.

PubMed

Li, Zhongshan; Liu, Zhenwei; Jiang, Yi; Chen, Denghui; Ran, Xia; Sun, Zhong Sheng; Wu, Jinyu

2017-01-01

Exome sequencing has been widely used to identify the genetic variants underlying human genetic disorders for clinical diagnoses, but the identification of pathogenic sequence variants among the huge amounts of benign ones is complicated and challenging. Here, we describe a new Web server named mirVAFC for pathogenic sequence variants prioritizations from clinical exome sequencing (CES) variant data of single individual or family. The mirVAFC is able to comprehensively annotate sequence variants, filter out most irrelevant variants using custom criteria, classify variants into different categories as for estimated pathogenicity, and lastly provide pathogenic variants prioritizations based on classifications and mutation effects. Case studies using different types of datasets for different diseases from publication and our in-house data have revealed that mirVAFC can efficiently identify the right pathogenic candidates as in original work in each case. Overall, the Web server mirVAFC is specifically developed for pathogenic sequence variant identifications from family-based CES variants using classification-based prioritizations. The mirVAFC Web server is freely accessible at https://www.wzgenomics.cn/mirVAFC/. © 2016 WILEY PERIODICALS, INC.

Current Trends in Plague Research: From Genomics to Virulence

PubMed Central

Huang, Xiao-Zhe; Nikolich, Mikeljon P.; Lindler, Luther E.

2006-01-01

Yersinia pestis is the causative agent of plague, which diverged from Yersinia pseudotuberculosis within the past 20,000 years.Although these two species share a high degree of homology at the DNA level (>90%), they differ radically in their pathogenicity and transmission. In this review, we briefly outline the known virulence factors that differentiate these two species and emphasize genetic studies that have been conducted comparing Y. pestis and Y. pseudotuberculosis.These comparisons have led to a better understanding of the genetic contributions to the differences in the virulence and pathogenicity between these two organisms and have generated information that can be applied in future diagnostic and vaccine development. Comparison of the genetic differences between Y. pestis and Y. pseudotuberculosis has also lent insight into the emergence of acute pathogens from organisms causing milder diseases. PMID:16988099

Attenuated CagA oncoprotein in Helicobacter pylori from Amerindians in Peruvian Amazon.

PubMed

Suzuki, Masato; Kiga, Kotaro; Kersulyte, Dangeruta; Cok, Jaime; Hooper, Catherine C; Mimuro, Hitomi; Sanada, Takahito; Suzuki, Shiho; Oyama, Masaaki; Kozuka-Hata, Hiroko; Kamiya, Shigeru; Zou, Quan-Ming; Gilman, Robert H; Berg, Douglas E; Sasakawa, Chihiro

2011-08-26

Population genetic analyses of bacterial genes whose products interact with host tissues can give new understanding of infection and disease processes. Here we show that strains of the genetically diverse gastric pathogen Helicobacter pylori from Amerindians from the remote Peruvian Amazon contain novel alleles of cagA, a major virulence gene, and reveal distinctive properties of their encoded CagA proteins. CagA is injected into the gastric epithelium where it hijacks pleiotropic signaling pathways, helps Hp exploit its special gastric mucosal niche, and affects the risk that infection will result in overt gastroduodenal diseases including gastric cancer. The Amerindian CagA proteins contain unusual but functional tyrosine phosphorylation motifs and attenuated CRPIA motifs, which affect gastric epithelial proliferation, inflammation, and bacterial pathogenesis. Amerindian CagA proteins induced less production of IL-8 and cancer-associated Mucin 2 than did those of prototype Western or East Asian strains and behaved as dominant negative inhibitors of action of prototype CagA during mixed infection of Mongolian gerbils. We suggest that Amerindian cagA is of relatively low virulence, that this may have been selected in ancestral strains during infection of the people who migrated from Asia into the Americas many thousands of years ago, and that such attenuated CagA proteins could be useful therapeutically.

Single gene reassortment of highly pathogenic avian influenza A H5N1 in the low pathogenic H9N2 backbone and its impact on pathogenicity and infectivity of novel reassortant viruses.

PubMed

Moatasim, Yassmin; Kandeil, Ahmed; Mostafa, Ahmed; Elghaffar, Sary Khaleel Abd; El Shesheny, Rabeh; Elwahy, Ahmed Helmy M; Ali, Mohamed Ahmed

2017-10-01

Avian influenza A H5N1 and H9N2 viruses have been extensively circulating in various avian species and frequently infect mammals, including humans. The synchronous circulation of both viruses in Egypt provides an opportunity for possible genetic assortment, posing a probable threat to global public health. To assess the potential risk of the IAV reassortants derived from co-circulation of these two AI subtypes, reverse genetics technology was used to generate a set of IAV reassortants carrying single genetic segments of clade 2.2.1.2 virus A/duck/Egypt/Q4596D/2012 (H5N1), a representative of the most prevalent H5N1 clade in Egypt, in the genetic backbone of A/chicken/Egypt/S4456B/2011 (H9N2), a representative of G1-like H9N2 lineage which is widely circulating in Egypt. Furthermore, the genetic compatibility, growth kinetics and virulence were evaluated in vitro in mammalian systems using the MDCK cell line and avian system using SPF embryonated chicken eggs. Pathogenicity and virus shedding were further tested using SPF chickens. Out of the eight desired H9-reassortants, we could rescue only 5 reassortant viruses, either due to difficulty in cloning (PB1 of H5N1 virus) or genetic incompatibility (NP-H5/H9 and NA-H5/H9). Results revealed higher replication rates for the H9N2 virus having the NS segment of H5N1 virus. The lowest survival rate in both SPF eggs and SPF chickens was associated with the H5N1 parent virus infection, followed by the HA-H5/H9 virus. Our findings also suggest that all other reassortant viruses were of lower pathogenicity than the wild type H5N1 virus.

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

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.

Pathogen-mediated selection in free-ranging elk populations infected by chronic wasting disease

USDA-ARS?s Scientific Manuscript database

Pathogens can exert a large influence on the evolution of hosts via selection for alleles or genotypes that moderate pathogen virulence. Inconsistent interactions between parasites and the host genome, such as those resulting from genetic linkages and environmental stochasticity, have largely preven...

Lack of host specialization on winter annual grasses in the fungal seed bank pathogen Pyrenophora semeniperda

Treesearch

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

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...

The multigenic nature of the differences in pathogenicity of H5N1 highly pathogenic avian influenza viruses in domestic ducks

USDA-ARS?s Scientific Manuscript database

The Eurasian H5N1 highly pathogenic avian influenza (HPAI) viruses have evolved into many genetic lineages. The divergent strains that have arisen express distinct pathobiological features and increased virulence for many bird species including domestic waterfowl. The pathogenicity of H5N1 HPAI vi...

Transient virulence of emerging pathogens.

PubMed

Bolker, Benjamin M; Nanda, Arjun; Shah, Dharmini

2010-05-06

Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

Transient virulence of emerging pathogens

PubMed Central

Bolker, Benjamin M.; Nanda, Arjun; Shah, Dharmini

2010-01-01

Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution. PMID:19864267

Molecular phylogeny, pathogenicity and toxigenicity of Fusarium oxysporum f. sp. lycopersici

PubMed Central

Nirmaladevi, D.; Venkataramana, M.; Srivastava, Rakesh K.; Uppalapati, S. R.; Gupta, Vijai Kumar; Yli-Mattila, T.; Clement Tsui, K. M.; Srinivas, C.; Niranjana, S. R.; Chandra, Nayaka S.

2016-01-01

The present study aimed at the molecular characterization of pathogenic and non pathogenic F. oxysporum f. sp. lycopersici strains isolated from tomato. The causal agent isolated from symptomatic plants and soil samples was identified based on morphological and molecular analyses. Pathogenicity testing of 69 strains on five susceptible tomato varieties showed 45% of the strains were highly virulent and 30% were moderately virulent. Molecular analysis based on the fingerprints obtained through ISSR indicated the presence of wide genetic diversity among the strains. Phylogenetic analysis based on ITS sequences showed the presence of at least four evolutionary lineages of the pathogen. The clustering of F. oxysporum with non pathogenic isolates and with the members of other formae speciales indicated polyphyletic origin of F. oxysporum f. sp. lycopersici. Further analysis revealed intraspecies variability and nucleotide insertions or deletions in the ITS region among the strains in the study and the observed variations were found to be clade specific. The high genetic diversity in the pathogen population demands for development of effective resistance breeding programs in tomato. Among the pathogenic strains tested, toxigenic strains harbored the Fum1 gene clearly indicating that the strains infecting tomato crops have the potential to produce Fumonisin. PMID:26883288

Global Genetics and Invasion History of the Potato Powdery Scab Pathogen, Spongospora subterranea f.sp. subterranea

PubMed Central

Gau, Rebecca D.; Merz, Ueli; Falloon, Richard E.; Brunner, Patrick C.

2013-01-01

Spongospora subterranea f. sp. subterranea (Sss) causes two diseases on potato (Solanum tuberosum), lesions on tubers and galls on roots, which are economically important worldwide. Knowledge of global genetic diversity and population structure of pathogens is essential for disease management including resistance breeding. A combination of microsatellite and DNA sequence data was used to investigate the structure and invasion history of Sss. South American populations (four countries, 132 samples) were consistently more diverse than those from all other regions (15 countries, 566 samples), in agreement with the hypothesis that Sss originated in South America where potato was domesticated. A substantial genetic differenciation was found between root and tuber-derived samples from South America. Estimates of past and recent gene flow suggested that Sss was probably introduced from South America into Europe. Subsequently, Europe is likely to have been the recent source of migrants of the pathogen, acting as a “bridgehead” for further global dissemination. Quarantine measures must continue to be focussed on maintaining low global genetic diversity and avoiding exchange of genetic material between the native and introduced regions. Nevertheless, the current low global genetic diversity of Sss allows potato breeders to select for resistance, which is likely to be durable. PMID:23840791

Cryptic chytridiomycosis linked to climate and genetic variation in amphibian populations of the southeastern United States

PubMed Central

Hoffman, Eric A.; Tye, Matthew R.; Hether, Tyler D.; Savage, Anna E.

2017-01-01

North American amphibians have recently been impacted by two major emerging pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and iridoviruses in the genus Ranavirus (Rv). Environmental factors and host genetics may play important roles in disease dynamics, but few studies incorporate both of these components into their analyses. Here, we investigated the role of environmental and genetic factors in driving Bd and Rv infection prevalence and severity in a biodiversity hot spot, the southeastern United States. We used quantitative PCR to characterize Bd and Rv dynamics in natural populations of three amphibian species: Notophthalmus perstriatus, Hyla squirella and Pseudacris ornata. We combined pathogen data, genetic diversity metrics generated from neutral markers, and environmental variables into general linear models to evaluate how these factors impact infectious disease dynamics. Occurrence, prevalence and intensity of Bd and Rv varied across species and populations, but only one species, Pseudacris ornata, harbored high Bd intensities in the majority of sampled populations. Genetic diversity and climate variables both predicted Bd prevalence, whereas climatic variables alone predicted infection intensity. We conclude that Bd is more abundant in the southeastern United States than previously thought and that genetic and environmental factors are both important for predicting amphibian pathogen dynamics. Incorporating both genetic and environmental information into conservation plans for amphibians is necessary for the development of more effective management strategies to mitigate the impact of emerging infectious diseases. PMID:28448517

Genetic diversity of highly pathogenic H5N8 avian influenza viruses at a single overwintering site of migratory birds in Japan, 2014/15.

PubMed

Ozawa, M; Matsuu, A; Tokorozaki, K; Horie, M; Masatani, T; Nakagawa, H; Okuya, K; Kawabata, T; Toda, S

2015-05-21

We isolated eight highly pathogenic H5N8 avian influenza viruses (H5N8 HPAIVs) in the 2014/15 winter season at an overwintering site of migratory birds in Japan. Genetic analyses revealed that these isolates were divided into three groups, indicating the co-circulation of three genetic groups of H5N8 HPAIV among these migratory birds. These results also imply the possibility of global redistribution of the H5N8 HPAIVs via the migration of these birds next winter.

Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System.

PubMed

Kinoshita, Moritoshi; Higashihara, Eiji; Kawano, Haruna; Higashiyama, Ryo; Koga, Daisuke; Fukui, Takafumi; Gondo, Nobuhisa; Oka, Takehiko; Kawahara, Kozo; Rigo, Krisztina; Hague, Tim; Katsuragi, Kiyonori; Sudo, Kimiyoshi; Takeshi, Masahiko; Horie, Shigeo; Nutahara, Kikuo

2016-01-01

Genetic testing of PKD1 and PKD2 is expected to play an increasingly important role in determining allelic influences in autosomal dominant polycystic kidney disease (ADPKD) in the near future. However, to date, genetic testing is not commonly employed because it is expensive, complicated because of genetic heterogeneity, and does not easily identify pathogenic variants. In this study, we developed a genetic testing system based on next-generation sequencing (NGS), long-range polymerase chain reaction, and a new software package. The new software package integrated seven databases and provided access to five cloud-based computing systems. The database integrated 241 polymorphic nonpathogenic variants detected in 140 healthy Japanese volunteers aged >35 years, who were confirmed by ultrasonography as having no cysts in either kidney. Using this system, we identified 60 novel and 30 known pathogenic mutations in 101 Japanese patients with ADPKD, with an overall detection rate of 89.1% (90/101) [95% confidence interval (CI), 83.0%-95.2%]. The sensitivity of the system increased to 93.1% (94/101) (95% CI, 88.1%-98.0%) when combined with multiplex ligation-dependent probe amplification analysis, making it sufficient for use in a clinical setting. In 82 (87.2%) of the patients, pathogenic mutations were detected in PKD1 (95% CI, 79.0%-92.5%), whereas in 12 (12.8%) patients pathogenic mutations were detected in PKD2 (95% CI, 7.5%-21.0%); this is consistent with previously reported findings. In addition, we were able to reconfirm our pathogenic mutation identification results using Sanger sequencing. In conclusion, we developed a high-sensitivity NGS-based system and successfully employed it to identify pathogenic mutations in PKD1 and PKD2 in Japanese patients with ADPKD.

Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.

PubMed

Vinayak, Sumiti; Pawlowic, Mattie C; Sateriale, Adam; Brooks, Carrie F; Studstill, Caleb J; Bar-Peled, Yael; Cipriano, Michael J; Striepen, Boris

2015-07-23

Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

PubMed

Johnson, Ben; Lowe, Gillian C; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula Hb; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E; Watson, Steve P; Morgan, Neil V

2016-10-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×10 9 /L to 186×10 9 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. Copyright© Ferrata Storti Foundation.

Wide variation in virulence and genetic diversity of binucleate Rhizoctonia isolates associated with root rot of strawberry in Western Australia.

PubMed

Fang, Xiangling; Finnegan, Patrick M; Barbetti, Martin J

2013-01-01

Strawberry (Fragaria×ananassa) is one of the most important berry crops in the world. Root rot of strawberry caused by Rhizoctonia spp. is a serious threat to commercial strawberry production worldwide. However, there is no information on the genetic diversity and phylogenetic status of Rhizoctonia spp. associated with root rot of strawberry in Australia. To address this, a total of 96 Rhizoctonia spp. isolates recovered from diseased strawberry plants in Western Australia were characterized for their nuclear condition, virulence, genetic diversity and phylogenetic status. All the isolates were found to be binucleate Rhizoctonia (BNR). Sixty-five of the 96 BNR isolates were pathogenic on strawberry, but with wide variation in virulence, with 25 isolates having high virulence. Sequence analysis of the internal transcribed spacers of the ribosomal DNA separated the 65 pathogenic BNR isolates into six distinct clades. The sequence analysis also separated reference BNR isolates from strawberry or other crops across the world into clades that correspond to their respective anastomosis group (AG). Some of the pathogenic BNR isolates from this study were embedded in the clades for AG-A, AG-K and AG-I, while other isolates formed clades that were sister to the clades specific for AG-G, AG-B, AG-I and AG-C. There was no significant association between genetic diversity and virulence of these BNR isolates. This study demonstrates that pathogenic BNR isolates associated with root rot of strawberry in Western Australia have wide genetic diversity, and highlights new genetic groups not previously found to be associated with root rot of strawberry in the world (e.g., AG-B) or in Australia (e.g., AG-G). The wide variation in virulence and genetic diversity identified in this study will be of high value for strawberry breeding programs in selecting, developing and deploying new cultivars with resistance to these multi-genetic groups of BNR.

Phylogenetics of a Fungal Invasion: Origins and Widespread Dispersal of White-Nose Syndrome.

PubMed

Drees, Kevin P; Lorch, Jeffrey M; Puechmaille, Sebastien J; Parise, Katy L; Wibbelt, Gudrun; Hoyt, Joseph R; Sun, Keping; Jargalsaikhan, Ariunbold; Dalannast, Munkhnast; Palmer, Jonathan M; Lindner, Daniel L; Marm Kilpatrick, A; Pearson, Talima; Keim, Paul S; Blehert, David S; Foster, Jeffrey T

2017-12-12

Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates. Pseudogymnoascus destructans , a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has exhibited few genetic polymorphisms in previous studies, presenting challenges for both epizoological tracking of the spread of this fungus and for determining its evolutionary history. We used single nucleotide polymorphisms (SNPs) from whole-genome sequencing and microsatellites to construct high-resolution phylogenies of P. destructans Shallow genetic diversity and the lack of geographic structuring among North American isolates support a recent introduction followed by expansion via clonal reproduction across the epizootic zone. Moreover, the genetic relationships of isolates within North America suggest widespread mixing and long-distance movement of the fungus. Genetic diversity among isolates of P. destructans from Europe was substantially higher than in those from North America. However, genetic distance between the North American isolates and any given European isolate was similar to the distance between the individual European isolates. In contrast, the isolates we examined from Asia were highly divergent from both European and North American isolates. Although the definitive source for introduction of the North American population has not been conclusively identified, our data support the origin of the North American invasion by P. destructans from Europe rather than Asia. IMPORTANCE This phylogenetic study of the bat white-nose syndrome agent, P. destructans , uses genomics to elucidate evolutionary relationships among populations of the fungal pathogen to understand the epizoology of this biological invasion. We analyze hypervariable and abundant genetic characters (microsatellites and genomic SNPs, respectively) to reveal previously uncharacterized diversity among populations of the pathogen from North America and Eurasia. We present new evidence supporting recent introduction of the fungus to North America from a diverse Eurasian population, with limited increase in genetic variation in North America since that introduction. Copyright © 2017 Drees et al.

Determinants of Virulence and In Vitro Development Colocalize on a Genetic Map of Setosphaeria turcica.

PubMed

Mideros, Santiago X; Chung, Chia-Lin; Wiesner-Hanks, Tyr; Poland, Jesse A; Wu, Dongliang; Fialko, Ariel A; Turgeon, B Gillian; Nelson, Rebecca J

2018-02-01

Generating effective and stable strategies for resistance breeding requires an understanding of the genetics of host-pathogen interactions and the implications for pathogen dynamics and evolution. Setosphaeria turcica causes northern leaf blight (NLB), an important disease of maize for which major resistance genes have been deployed. Little is known about the evolutionary dynamics of avirulence (AVR) genes in S. turcica. To test the hypothesis that there is a genetic association between avirulence and in vitro development traits, we (i) created a genetic map of S. turcica, (ii) located candidate AVRHt1 and AVRHt2 regions, and (iii) identified genetic regions associated with several in vitro development traits. A cross was generated between a race 1 and a race 23N strain, and 221 progeny were isolated. Genotyping by sequencing was used to score 2,078 single-nucleotide polymorphism markers. A genetic map spanning 1,981 centimorgans was constructed, consisting of 21 linkage groups. Genetic mapping extended prior evidence for the location and identity of the AVRHt1 gene and identified a region of interest for AVRHt2. The genetic location of AVRHt2 colocalized with loci influencing radial growth and mycelial abundance. Our data suggest a trade-off between virulence on Ht1 and Ht2 and the pathogen's vegetative growth rate. In addition, in-depth analysis of the genotypic data suggests the presence of significant duplication in the genome of S. turcica.

Expanding the genetic toolbox for Leptospira species by generation of fluorescent bacteria.

PubMed

Aviat, Florence; Slamti, Leyla; Cerqueira, Gustavo M; Lourdault, Kristel; Picardeau, Mathieu

2010-12-01

Our knowledge of the genetics and molecular basis of the pathogenesis associated with Leptospira, in comparison to those of other bacterial species, is very limited. An improved understanding of pathogenic mechanisms requires reliable genetic tools for functional genetic analysis. Here, we report the expression of gfp and mRFP1 genes under the control of constitutive spirochetal promoters in both saprophytic and pathogenic Leptospira strains. We were able to reliably measure the fluorescence of Leptospira by fluorescence microscopy and a fluorometric microplate reader-based assay. We showed that the expression of the gfp gene had no significant effects on growth in vivo and pathogenicity in L. interrogans. We constructed an expression vector for L. biflexa that contains the lacI repressor, an inducible lac promoter, and gfp as the reporter, demonstrating that the lac system is functional in Leptospira. Green fluorescent protein (GFP) expression was induced by the addition of isopropyl-β-d-thiogalactopyranoside (IPTG) in L. biflexa transformants harboring the expression vector. Finally, we showed that GFP can be used as a reporter to assess promoter activity in different environmental conditions. These results may facilitate further advances for studying the genetics of Leptospira spp.

Three genetic groups of the Eucalyptus stem canker pathogen Teratosphaeria zuluensis introduced into Africa from an unknown source.

PubMed

Jimu, Luke; Chen, ShuaiFei; Wingfield, Michael J; Mwenje, Eddie; Roux, Jolanda

2016-01-01

The Eucalyptus stem canker pathogen Teratosphaeria zuluensis was discovered in South Africa in 1988 and it has subsequently been found in several other African countries as well as globally. In this study, the population structure, genetic diversity and evolutionary history of T. z uluensis were analysed using microsatellite markers to gain an enhanced understanding of its movement in Africa. Isolates were collected from several sites in Malawi, Mozambique, Uganda and Zambia. Data obtained were compared with those previously published for a South African population. The data obtained from 334 isolates, amplified across eight microsatellite loci, were used for assignment, differentiation and genetic diversity tests. STRUCTURE analyses, θ st and genetic distances revealed the existence of two clusters, one dominated by isolates from South Africa and the other by isolates from the Zambezi basin including Malawi, Mozambique and Zambia. High levels of admixture were found within and among populations, dominated by the Mulanje population in Malawi. Moderate to low genetic diversity of the populations supports the previously held view that the pathogen was introduced into Africa. The clonal nature of the Ugandan population suggests a very recent introduction, most likely from southern Africa.

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...

Characterization of Clade 2.3.2.1 H5N1 Highly Pathogenic Avian Influenza Viruses Isolated from Wild Birds (Mandarin Duck and Eurasian Eagle Owl) in 2010 in Korea

PubMed Central

Choi, Jun-Gu; Kang, Hyun-Mi; Jeon, Woo-Jin; Choi, Kang-Seuk; Kim, Kwang-Il; Song, Byung Min; Lee, Hee-Soo; Kim, Jae-Hong; Lee, Youn-Jeong

2013-01-01

Starting in late November 2010, the H5N1 highly pathogenic avian influenza (HPAI) virus was isolated from many types of wild ducks and raptors and was subsequently isolated from poultry in Korea. We assessed the genetic and pathogenic properties of the HPAI viruses isolated from a fecal sample from a mandarin duck and a dead Eurasian eagle owl, the most affected wild bird species during the 2010/2011 HPAI outbreak in Korea. These viruses have similar genetic backgrounds and exhibited the highest genetic similarity with recent Eurasian clade 2.3.2.1 HPAI viruses. In animal inoculation experiments, regardless of their originating hosts, the two Korean isolates produced highly pathogenic characteristics in chickens, ducks and mice without pre-adaptation. These results raise concerns about veterinary and public health. Surveillance of wild birds could provide a good early warning signal for possible HPAI infection in poultry as well as in humans. PMID:23611846

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST).

PubMed

Sakic, Boris; Cooper, Marcella P A; Taylor, Sarah E; Stojanovic, Milica; Zagorac, Bosa; Kapadia, Minesh

2015-04-23

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

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

From perception to activation: the molecular-genetic and biochemical landscape of disease resistance signaling in plants.

PubMed

Knepper, Caleb; Day, Brad

2010-01-01

More than 60 years ago, H.H. Flor proposed the "Gene-for-Gene" hypothesis, which described the genetic relationship between host plants and pathogens. In the decades that followed Flor's seminal work, our understanding of the plant-pathogen interaction has evolved into a sophisticated model, detailing the molecular genetic and biochemical processes that control host-range, disease resistance signaling and susceptibility. The interaction between plants and microbes is an intimate exchange of signals that has evolved for millennia, resulting in the modification and adaptation of pathogen virulence strategies and host recognition elements. In total, plants have evolved mechanisms to combat the ever-changing landscape of biotic interactions bombarding their environment, while in parallel, plant pathogens have co-evolved mechanisms to sense and adapt to these changes. On average, the typical plant is susceptible to attack by dozens of microbial pathogens, yet in most cases, remains resistant to many of these challenges. The sum of research in our field has revealed that these interactions are regulated by multiple layers of intimately linked signaling networks. As an evolved model of Flor's initial observations, the current paradigm in host-pathogen interactions is that pathogen effector molecules, in large part, drive the recognition, activation and subsequent physiological responses in plants that give rise to resistance and susceptibility. In this Chapter, we will discuss our current understanding of the association between plants and microbial pathogens, detailing the pressures placed on both host and microbe to either maintain disease resistance, or induce susceptibility and disease. From recognition to transcriptional reprogramming, we will review current data and literature that has advanced the classical model of the Gene-for-Gene hypothesis to our current understanding of basal and effector triggered immunity.

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

PubMed Central

Escaffre, Olivier; Le Nouën, Cyril; Amelot, Michel; Ambroggio, Xavier; Ogden, Kristen M.; Guionie, Olivier; Toquin, Didier; Müller, Hermann; Islam, Mohammed R.

2013-01-01

Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much as 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, and the relative contributions of the two genome segments, A and B, to this phenomenon are not known. Isolate 94432 has been shown previously to be genetically related to vvIBDVs but exhibits atypical antigenicity and does not cause mortality. Here the full-length genome of 94432 was determined, and a reverse genetics system was established. The molecular clone was rescued and exhibited the same antigenicity and reduced pathogenicity as isolate 94432. Genetically modified viruses derived from 94432, whose vvIBDV consensus nucleotide sequence was restored in segment A and/or B, were produced, and their pathogenicity was assessed in specific-pathogen-free chickens. We found that a valine (position 321) that modifies the most exposed part of the capsid protein VP2 critically modified the antigenicity and partially reduced the pathogenicity of 94432. However, a threonine (position 276) located in the finger domain of the virus polymerase (VP1) contributed even more significantly to attenuation. This threonine is partially exposed in a hydrophobic groove on the VP1 surface, suggesting possible interactions between VP1 and another, as yet unidentified molecule at this amino acid position. The restored vvIBDV-like pathogenicity was associated with increased replication and lesions in the thymus and spleen. These results demonstrate that both genome segments influence vvIBDV pathogenicity and may provide new targets for the attenuation of vvIBDVs. PMID:23269788

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

Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds

PubMed Central

Matsuu, Aya; Kobayashi, Tomoko; Patchimasiri, Tuangthong; Shiina, Takashi; Suzuki, Shingo; Chaichoune, Kridsada; Ratanakorn, Parntep; Hiromoto, Yasuaki; Abe, Haruka; Parchariyanon, Sujira; Saito, Takehiko

2016-01-01

Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV. PMID:27078641

Genetics and Psychiatry: Myth or Reality?

PubMed

Juli, Giada; Juli, Rebecca; Juli, Luigi

2017-09-01

Greek mythology and philosophical speculations were the first human productions on madness and psychiatry. Likewise, the origins of genetics sink their roots in a very remote and difficult time. This work tries to give an idea of the relationship between genetics and psychiatry through the myth and reality.

Delineating the genetic heterogeneity of OCA in Hungarian patients.

PubMed

Fábos, Beáta; Farkas, Katalin; Tóth, Lola; Sulák, Adrienn; Tripolszki, Kornélia; Tihanyi, Mariann; Németh, Réka; Vas, Krisztina; Csoma, Zsanett; Kemény, Lajos; Széll, Márta; Nagy, Nikoletta

2017-06-19

Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities characterized by variable hair, skin, and ocular hypopigmentation. Six known genes and a locus on human chromosome 4q24 have been implicated in the etiology of isolated OCA forms (OCA 1-7). The most frequent OCA types among Caucasians are OCA1, OCA2, and OCA4. We aimed to investigate genes responsible for the development of these OCA forms in Hungarian OCA patients (n = 13). Mutation screening and polymorphism analysis were performed by direct sequencing on TYR, OCA2, SLC45A2 genes. Although the clinical features of the investigated Hungarian OCA patients were identical, the molecular genetic data suggested OCA1 subtype in eight cases and OCA4 subtype in two cases. The molecular diagnosis was not clearly identifiable in three cases. In four patients, two different heterozygous known pathogenic or predicted to be pathogenic mutations were present. Seven patients had only one pathogenic mutation, which was associated with non-pathogenic variants in six cases. In two patients no pathogenic mutation was identified. Our results suggest that the concomitant screening of the non-pathogenic variants-which alone do not cause the development of OCA, but might have clinical significance in association with a pathogenic variant-is important. Our results also show significant variation in the disease spectrum compared to other populations. These data also confirm that the concomitant analysis of OCA genes is critical, providing new insights to the phenotypic diversity of OCA and expanding the mutation spectrum of OCA genes in Hungarian patients.

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

PubMed

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

2015-11-01

Recombination has an impact on genome evolution by maintaining chromosomal integrity, affecting the efficacy of selection, and increasing genetic variability in populations. Recombination rates are a key determinant of the coevolutionary dynamics between hosts and their pathogens. Historic recombination events created devastating new pathogens, but the impact of ongoing recombination in sexual pathogens is poorly understood. Many fungal pathogens of plants undergo regular sexual cycles, and sex is considered to be a major factor contributing to virulence. We generated a recombination map at kilobase-scale resolution for the haploid plant pathogenic fungus Zymoseptoria tritici. To account for intraspecific variation in recombination rates, we constructed genetic maps from two independent crosses. We localized a total of 10,287 crossover events in 441 progeny and found that recombination rates were highly heterogeneous within and among chromosomes. Recombination rates on large chromosomes were inversely correlated with chromosome length. Short accessory chromosomes often lacked evidence for crossovers between parental chromosomes. Recombination was concentrated in narrow hotspots that were preferentially located close to telomeres. Hotspots were only partially conserved between the two crosses, suggesting that hotspots are short-lived and may vary according to genomic background. Genes located in hotspot regions were enriched in genes encoding secreted proteins. Population resequencing showed that chromosomal regions with high recombination rates were strongly correlated with regions of low linkage disequilibrium. Hence, genes in pathogen recombination hotspots are likely to evolve faster in natural populations and may represent a greater threat to the host. Copyright © 2015 by the Genetics Society of America.

Trichoderma-plant-pathogen interactions: advances in genetics of biological control.

PubMed

Mukherjee, Mala; Mukherjee, Prasun K; Horwitz, Benjamin A; Zachow, Christin; Berg, Gabriele; Zeilinger, Susanne

2012-12-01

Trichoderma spp. are widely used in agriculture as biofungicides. Induction of plant defense and mycoparasitism (killing of one fungus by another) are considered to be the most important mechanisms of Trichoderma-mediated biological control. Understanding these mechanisms at the molecular level would help in developing strains with superior biocontrol properties. In this article, we review our current understanding of the genetics of interactions of Trichoderma with plants and plant pathogens.

The Complex Genetic Basis of Congenital Heart Defects

PubMed Central

Akhirome, Ehiole; Walton, Nephi A.; Nogee, Julie M.; Jay, Patrick Y.

2017-01-01

Twenty years ago, chromosomal abnormalities were the only identifiable genetic causes of a small fraction of congenital heart defects (CHD). Today, a de novo or inherited genetic abnormality can be identified as pathogenic in one-third of cases. We refer to them here as monogenic causes, insofar as the genetic abnormality has a readily detectable, large effect. What explains the other two-thirds? This review considers a complex genetic basis. That is, a combination of genetic mutations or variants that individually may have little or no detectable effect contribute to the pathogenesis of a heart defect. Genes in the embryo that act directly in cardiac developmental pathways have received the most attention, but genes in the mother that establish the gestational milieu via pathways related to metabolism and aging also have an effect. A growing body of evidence highlights the pathogenic significance of genetic interactions in the embryo and maternal effects that have a genetic basis. The investigation of CHD as guided by a complex genetic model could help estimate risk more precisely and logically lead to a means of prevention. PMID:28381817

Rapid emergence of pathogens in agro-ecosystems: global threats to agricultural sustainability and food security.

PubMed

McDonald, Bruce A; Stukenbrock, Eva H

2016-12-05

Agricultural ecosystems are composed of genetically depauperate populations of crop plants grown at a high density and over large spatial scales, with the regional composition of crop species changing little from year to year. These environments are highly conducive for the emergence and dissemination of pathogens. The uniform host populations facilitate the specialization of pathogens to particular crop cultivars and allow the build-up of large population sizes. Population genetic and genomic studies have shed light on the evolutionary mechanisms underlying speciation processes, adaptive evolution and long-distance dispersal of highly damaging pathogens in agro-ecosystems. These studies document the speed with which pathogens evolve to overcome crop resistance genes and pesticides. They also show that crop pathogens can be disseminated very quickly across and among continents through human activities. In this review, we discuss how the peculiar architecture of agro-ecosystems facilitates pathogen emergence, evolution and dispersal. We present four example pathosystems that illustrate both pathogen specialization and pathogen speciation, including different time frames for emergence and different mechanisms underlying the emergence process. Lastly, we argue for a re-design of agro-ecosystems that embraces the concept of dynamic diversity to improve their resilience to pathogens. This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Author(s).

Genetic variants in post myocardial infarction patients presenting with electrical storm of unstable ventricular tachycardia.

PubMed

Rangaraju, Advithi; Krishnan, Shuba; Aparna, G; Sankaran, Satish; Mannan, Ashraf U; Rao, B Hygriv

2018-01-30

Electrical storm (ES) is a life threatening clinical situation. Though a few clinical pointers exist, the occurrence of ES in a patient with remote myocardial infarction (MI) is generally unpredictable. Genetic markers for this entity have not been studied. In the present study, we carried out genetic screening in patients with remote myocardial infarction presenting with ES by next generation sequencing and identified 25 rare variants in 19 genes predominantly in RYR2, SCN5A, KCNJ11, KCNE1 and KCNH2, CACNA1B, CACNA1C, CACNA1D and desmosomal genes - DSP and DSG2 that could potentially be implicated in electrical storm. These genes have been previously reported to be associated with inherited syndromes of Sudden Cardiac Death. The present study suggests that the genetic architecture in patients with remote MI and ES of unstable ventricular tachycardia may be similar to that of Ion channelopathies. Identification of these variants may identify post MI patients who are predisposed to develop electrical storm and help in risk stratification. Copyright © 2018 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

Comprehensive analysis of the mutation spectrum in 301 German ALS families.

PubMed

Müller, Kathrin; Brenner, David; Weydt, Patrick; Meyer, Thomas; Grehl, Torsten; Petri, Susanne; Grosskreutz, Julian; Schuster, Joachim; Volk, Alexander E; Borck, Guntram; Kubisch, Christian; Klopstock, Thomas; Zeller, Daniel; Jablonka, Sibylle; Sendtner, Michael; Klebe, Stephan; Knehr, Antje; Günther, Kornelia; Weis, Joachim; Claeys, Kristl G; Schrank, Berthold; Sperfeld, Anne-Dorte; Hübers, Annemarie; Otto, Markus; Dorst, Johannes; Meitinger, Thomas; Strom, Tim M; Andersen, Peter M; Ludolph, Albert C; Weishaupt, Jochen H

2018-04-12

Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions. Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families. 49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1 , whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes. We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe. © 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.

Genetic modification of Anopheles stephensi for resistance to multiple Plasmodium falciparum strains does not influence susceptibility to o'nyong'nyong virus or insecticides, or Wolbachia-mediated resistance to the malaria parasite.

PubMed

Pike, Andrew; Dimopoulos, George

2018-01-01

Mosquitoes that have been genetically engineered for resistance to human pathogens are a potential new tool for controlling vector-borne disease. However, genetic modification may have unintended off-target effects that could affect the mosquitoes' utility for disease control. We measured the resistance of five genetically modified Plasmodium-suppressing Anopheles stephensi lines to o'nyong'nyong virus, four classes of insecticides, and diverse Plasmodium falciparum field isolates and characterized the interactions between our genetic modifications and infection with the bacterium Wolbachia. The genetic modifications did not alter the mosquitoes' resistance to either o'nyong'nyong virus or insecticides, and the mosquitoes were equally resistant to all tested P. falciparum strains, regardless of Wolbachia infection status. These results indicate that mosquitoes can be genetically modified for resistance to malaria parasite infection and remain compatible with other vector-control measures without becoming better vectors for other pathogens.

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.

Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise.

PubMed

Giudicessi, John R; Ackerman, Michael J

2013-01-01

In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.

Genetic engineering of microbial pesticides

Treesearch

Bruce C. Carlton

1985-01-01

Recent advances in genetics and molecular biology make possible the cloning and genetic manipulation of genes for insecticidal activities from natural insect pathogens. Using recombinant DNA methods and site-directed mutagenesis of specific gene regions, production of new and improved biorationals should be possible.

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

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

PubMed

Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

2018-01-01

Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

Pathogen reduction requirements for direct potable reuse in Antarctica: evaluating human health risks in small communities.

PubMed

Barker, S Fiona; Packer, Michael; Scales, Peter J; Gray, Stephen; Snape, Ian; Hamilton, Andrew J

2013-09-01

Small, remote communities often have limited access to energy and water. Direct potable reuse of treated wastewater has recently gained attention as a potential solution for water-stressed regions, but requires further evaluation specific to small communities. The required pathogen reduction needed for safe implementation of direct potable reuse of treated sewage is an important consideration but these are typically quantified for larger communities and cities. A quantitative microbial risk assessment (QMRA) was conducted, using norovirus, giardia and Campylobacter as reference pathogens, to determine the level of treatment required to meet the tolerable annual disease burden of 10(-6) DALYs per person per year, using Davis Station in Antarctica as an example of a small remote community. Two scenarios were compared: published municipal sewage pathogen loads and estimated pathogen loads during a gastroenteritis outbreak. For the municipal sewage scenario, estimated required log10 reductions were 6.9, 8.0 and 7.4 for norovirus, giardia and Campylobacter respectively, while for the outbreak scenario the values were 12.1, 10.4 and 12.3 (95th percentiles). Pathogen concentrations are higher under outbreak conditions as a function of the relatively greater degree of contact between community members in a small population, compared with interactions in a large city, resulting in a higher proportion of the population being at risk of infection and illness. While the estimates of outbreak conditions may overestimate sewage concentration to some degree, the results suggest that additional treatment barriers would be required to achieve regulatory compliance for safe drinking water in small communities. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparative genomics of a plant-pathogenic fungus, Pyrenophora tritici-repentis, reveals transduplication and the impact of repeat elements on pathogenicity and population divergence. G3-Genes, Genomes, Genetics.

USDA-ARS?s Scientific Manuscript database

Pyrenophora tritici-repentis is a necrotrophic fungal pathogen and causal agent of tan spot disease of wheat, which has increased significantly over the last few decades. Pathogenicity by this fungus is due to host-selective toxins. These toxins are recognized by their host plant in a genotype-speci...

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

Treesearch

R.A. Sniezko; L.A. Winn

2017-01-01

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

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

PubMed

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

2015-04-01

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

A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens.

PubMed

Cameron, Andrew; Klima, Cassidy L; Ha, Reuben; Gruninger, Robert J; Zaheer, Rahat; McAllister, Tim A

2018-01-01

A novel variant of the AAD(3″) class of aminoglycoside-modifying enzymes was discovered in fatal bovine respiratory disease-associated pathogens Pasteurella multocida and Histophilus somni . The aadA31 gene encodes a spectinomycin/streptomycin adenylyltransferase and was located in a variant of the integrative and conjugative element ICE Mh1 , a mobile genetic element transmissible among members of the family Pasteurellaceae . The gene was also detected in Mannheimia haemolytica from a case of porcine pneumonia and in Moraxella bovoculi from a case of keratoconjunctivitis. IMPORTANCE Aminoglycosides are important antimicrobials used worldwide for prophylaxis and/or therapy in multiple production animal species. The emergence of new resistance genes jeopardizes current pathogen detection and treatment methods. The risk of resistance gene transfer to other animal and human pathogens is elevated when resistance genes are carried by mobile genetic elements. This study identified a new variant of a spectinomycin/streptomycin resistance gene harbored in a self-transmissible mobile element. The gene was also present in four different bovine pathogen species.

A Novel aadA Aminoglycoside Resistance Gene in Bovine and Porcine Pathogens

PubMed Central

Cameron, Andrew; Klima, Cassidy L.; Ha, Reuben; Gruninger, Robert J.; Zaheer, Rahat

2018-01-01

ABSTRACT A novel variant of the AAD(3″) class of aminoglycoside-modifying enzymes was discovered in fatal bovine respiratory disease-associated pathogens Pasteurella multocida and Histophilus somni. The aadA31 gene encodes a spectinomycin/streptomycin adenylyltransferase and was located in a variant of the integrative and conjugative element ICEMh1, a mobile genetic element transmissible among members of the family Pasteurellaceae. The gene was also detected in Mannheimia haemolytica from a case of porcine pneumonia and in Moraxella bovoculi from a case of keratoconjunctivitis. IMPORTANCE Aminoglycosides are important antimicrobials used worldwide for prophylaxis and/or therapy in multiple production animal species. The emergence of new resistance genes jeopardizes current pathogen detection and treatment methods. The risk of resistance gene transfer to other animal and human pathogens is elevated when resistance genes are carried by mobile genetic elements. This study identified a new variant of a spectinomycin/streptomycin resistance gene harbored in a self-transmissible mobile element. The gene was also present in four different bovine pathogen species. PMID:29507894

PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen Genetic Diversity

PubMed Central

Hall, Matthew; Ratmann, Oliver; Bonsall, David; Golubchik, Tanya; de Cesare, Mariateresa; Gall, Astrid; Cornelissen, Marion; Fraser, Christophe

2018-01-01

Abstract A central feature of pathogen genomics is that different infectious particles (virions and bacterial cells) within an infected individual may be genetically distinct, with patterns of relatedness among infectious particles being the result of both within-host evolution and transmission from one host to the next. Here, we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. Multiply infected individuals are also identified, as they harbor subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform, and Streptococcus pneumoniae with sequences from multiple colonies per individual. phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner. PMID:29186559

Population Genetic Structure of Apple Scab (Venturia inaequalis (Cooke) G. Winter) in Iran

PubMed Central

Ebrahimi, Leila; Fotuhifar, Khalil-Berdi; Javan Nikkhah, Mohammad; Naghavi, Mohammad-Reza; Baisakh, Niranjan

2016-01-01

The population genetic structure of 278 Venturia inaequalis isolates, collected from different apple cultivars of eighteen different provinces in Iran, was investigated using 22 polymorphic microsatellite markers. Analysis of molecular variation, Bayesian clustering and Nei's genetic distance analyses based on 88 microsatellite alleles indicated substantial levels of gene flow among the collection sites. Ninety three percent of the variation was observed among the individuals within the populations and only 7% variation was observed among the populations. Structure analysis grouped the isolates into two populations. Maximum number of pathogen genotypes (44) was observed in the North of Iran that grows various different apple cultivars. Investigation on the variation of the pathogen on different cultivars in the North of Iran suggested a significant differentiation of the pathogen populations between wild apple and commercial cultivars. During sampling, varying ranges of scab infection were observed on various apple cultivars in forests, monoculture and mix orchards. Wild type apple (Malus orientalis) along the Caspian Sea Coast had the most infection in comparison with the Iranian endemic and commercial cultivars. Based on the genetic analysis and host tracking scenario of the pathogen, it was presumed that Iran could potentially be the center of origin of V. inaequalis, which requires further detailed studies with isolates collected from different parts of central Asia and world for confirmation. PMID:27631622

Clinical and genetic features of Australian families with long QT syndrome: A registry-based study.

PubMed

Burns, Charlotte; Ingles, Jodie; Davis, Andrew M; Connell, Vanessa; Gray, Belinda; Hunt, Lauren; McGaughran, Julie; Semsarian, Christopher

2016-12-01

Familial long QT syndrome (LQTS) is a primary arrhythmogenic disorder caused by mutations in ion channel genes. The phenotype ranges from asymptomatic individuals to sudden cardiac arrest and death. LQTS is a rare but significant health problem for which global data should exist. This study sought to provide the first clinical and genetic description of Australian families with LQTS. We performed a cross-sectional study to evaluate clinical and genetic features of families with LQTS. We recruited individuals from the Australian Genetic Heart Disease Registry and Genetic Heart Disease Clinic, in Sydney, Australia, and included those with a diagnosis of LQTS according to the most recent consensus statement. Among 108 families with LQTS, 173 individuals were affected. Twenty-five (32%) probands had a sudden cardiac death (SCD) event (including appropriate implantable cardioverter defibrillator [ICD] therapy, or resuscitated cardiac arrest). There were 64 (82%) probands who underwent genetic testing, and 34 (53%) had a pathogenic or likely pathogenic mutation in. Having a family history of LQTS was significantly associated with identification of a pathogenic result (79% versus 14%, p <0.0001). There were 16 (9%) participants who experienced delay to diagnosis of at least 12 months. This is the first clinical and genetic study in a large cohort of Australian families with LQTS. Findings from this study suggest that the clinical and genetic features in this population are not dissimilar to those described in North American, European, and Asian cohorts. Global-scale information about families with LQTS is an important initiative to ensure diagnostic and management approaches are applicable to different populations and ethnicities.

Monomorphic pathogens: The case of Candidatus Xenohaliotis californiensis from abalone in California, USA and Baja California, Mexico.

PubMed

Cicala, Francesco; Moore, James D; Cáceres-Martínez, Jorge; Del Río-Portilla, Miguel A; Hernández-Rodríguez, Mónica; Vásquez-Yeomans, Rebeca; Rocha-Olivares, Axayácatl

2018-05-01

Withering syndrome (WS) is a chronic wasting disease affecting abalone species attributed to the pathogen Candidatus Xenohaliotis californiensis (CXc). Wild populations of blue (Haliotis fulgens) and yellow (H. corrugata) abalone have experienced unusual mortality rates since 2009 off the peninsula of Baja California and WS has been hypothesized as a possible cause. Currently, little information is available about the genetic diversity of CXc and particularly the possible existence of strains differing in pathogenicity. In a recent phylogenetic analysis, we characterized five coding genes from this rickettsial pathogen. Here, we analyze those genes and two additional intergenic non-coding regions following multi-locus sequence typing (MLST) and multi-spacer typing (MST) approaches to assess the genetic variability of CXc and its relationship with blue, yellow and red (H. rufescens) abalone. Moreover, we used 16S rRNA pyrosequencing reads from gut microbiomes of blue and yellow abalone to complete the genetic characterization of this prokaryote. The presence of CXc was investigated in more than 150 abalone of the three species; furthermore, a total of 385 DNA sequences and 7117 16S rRNA reads from Candidatus Xenohaliotis californiensis were used to evaluate its population genetic structure. Our findings suggest the absence of polymorphism in the DNA sequences of analyzed loci and the presence of a single lineage of CXc infecting abalone from California (USA) and Baja California (Mexico). We posit that the absence of genetic variably in this marine rickettsia may be the result of evolutionary and ecological processes. Copyright © 2018 Elsevier Inc. All rights reserved.

Buried treasure: evolutionary perspectives on microbial iron piracy

PubMed Central

Barber, Matthew F.; Elde, Nels C.

2015-01-01

Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease. PMID:26431675

High Variation in Pathogenicity of Genetically Closely Related Strains of Xanthomonas albilineans, the Sugarcane Leaf Scald Pathogen, in Guadeloupe.

PubMed

Champoiseau, P; Daugrois, J-H; Pieretti, I; Cociancich, S; Royer, M; Rott, P

2006-10-01

ABSTRACT Pathogenicity of 75 strains of Xanthomonas albilineans from Guadeloupe was assessed by inoculation of sugarcane cv. B69566, which is susceptible to leaf scald, and 19 of the strains were selected as representative of the variation in pathogenicity observed based on stalk colonization. In vitro production of albicidin varied among these 19 strains, but the restriction fragment length polymorphism pattern of their albicidin biosynthesis genes was identical. Similarly, no genomic variation was found among strains by pulsed-field gel electrophoresis. Some variation among strains was found by amplified fragment length polymorphism, but no relationship between this genetic variation and variation in pathogenicity was found. Only 3 (pilB, rpfA, and xpsE) of 40 genes involved in pathogenicity of bacterial species closely related to X. albilineans could be amplified by polymerase chain reaction from total genomic DNA of all nine strains tested of X. albilineans differing in pathogenicity in Guadeloupe. Nucleotide sequences of these genes were 100% identical among strains, and a phylogenetic study with these genes and housekeeping genes efp and ihfA suggested that X. albilineans is on an evolutionary road between the X. campestris group and Xylella fastidiosa, another vascular plant pathogen. Sequencing of the complete genome of Xanthomonas albilineans could be the next step in deciphering molecular mechanisms involved in pathogenicity of X. albilineans.

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

PubMed

Wilfert, L; Jiggins, F M

2010-07-01

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

Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs.

PubMed

von Stülpnagel, C; Ensslen, M; Møller, R S; Pal, D K; Masnada, S; Veggiotti, P; Piazza, E; Dreesmann, M; Hartlieb, T; Herberhold, T; Hughes, E; Koch, M; Kutzer, C; Hoertnagel, K; Nitanda, J; Pohl, M; Rostásy, K; Haack, T B; Stöhr, K; Kluger, G; Borggraefe, I

2017-05-01

To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. 7 out of 19 patients fulfilled the ACMG-criteria of carrying "pathogenic" or "likely pathogenic variants", in twelve patients the alterations were classified as variants of unknown significance. The spectrum of pathogenic/likely pathogenic mutations was as follows: nonsense n = 3, missense n = 2, duplications/deletions n = 1 and splice site n = 1. First seizures occurred at a mean age of 2.4 years with heterogeneous seizure types. Patients were treated with a mean of 5.6 AED. 4/5 patients with VPA had an improved seizure frequency (n = 3 with a truncation: n = 1 missense). 3/5 patients with STM reported an improvement of seizures (n = 2 truncation, n = 1 splicing). 3/5 CLB patients showed an improvement (n = 2: truncation; n = 1 splicing). Steroids were reported to have a positive effect on seizure frequency in 3/5 patients (n = 1 each truncation, splicing or deletion). Our data indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic syndrome. Copyright © 2017 European Paediatric Neurology Society. All rights reserved.

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

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.

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.

A CRISPR Cas9-based gene drive platform for genetic interaction analysis in Candida albicans

PubMed Central

Shapiro, Rebecca S.; Chavez, Alejandro; Porter, Caroline B. M.; Hamblin, Meagan; Kaas, Christian S.; DiCarlo, James E.; Zeng, Guisheng; Xu, Xiaoli; Revtovich, Alexey V.; Kirienko, Natalia V.; Wang, Yue; Church, George M.; Collins, James J.

2018-01-01

Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR-Cas9-based ‘gene drive array’ (GDA) platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site, and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants. We generate double-gene deletion libraries to demonstrate this technology, targeting antifungal efflux and biofilm adhesion factors. We screen these libraries to identify virulence regulators and determine how genetic networks shift under diverse conditions. This platform transforms our ability to perform genetic interaction analysis in C. albicans and is readily extended to other fungal pathogens. PMID:29062088

Immunological Change in a Parasite-Impoverished Environment: Divergent Signals from Four Island Taxa

PubMed Central

Beadell, Jon S.; Atkins, Colm; Cashion, Erin; Jonker, Michelle; Fleischer, Robert C.

2007-01-01

Dramatic declines of native Hawaiian avifauna due to the human-mediated emergence of avian malaria and pox prompted an examination of whether island taxa share a common altered immunological signature, potentially driven by reduced genetic diversity and reduced exposure to parasites. We tested this hypothesis by characterizing parasite prevalence, genetic diversity and three measures of immune response in two recently-introduced species (Neochmia temporalis and Zosterops lateralis) and two island endemics (Acrocephalus aequinoctialis and A. rimitarae) and then comparing the results to those observed in closely-related mainland counterparts. The prevalence of blood parasites was significantly lower in 3 of 4 island taxa, due in part to the absence of certain parasite lineages represented in mainland populations. Indices of genetic diversity were unchanged in the island population of N. temporalis; however, allelic richness was significantly lower in the island population of Z. lateralis while both allelic richness and heterozygosity were significantly reduced in the two island-endemic species examined. Although parasite prevalence and genetic diversity generally conformed to expectations for an island system, we did not find evidence for a pattern of uniformly altered immune responses in island taxa, even amongst endemic taxa with the longest residence times. The island population of Z. lateralis exhibited a significantly reduced inflammatory cell-mediated response while levels of natural antibodies remained unchanged for this and the other recently introduced island taxon. In contrast, the island endemic A. rimitarae exhibited a significantly increased inflammatory response as well as higher levels of natural antibodies and complement. These measures were unchanged or lower in A. aequinoctialis. We suggest that small differences in the pathogenic landscape and the stochastic history of mutation and genetic drift are likely to be important in shaping the unique immunological profiles of small isolated populations. Consequently, predicting the impact of introduced disease on the many other endemic faunas of the remote Pacific will remain a challenge. PMID:17878931

Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter baumannii

PubMed Central

Ramage, Elizabeth; Weiss, Eli J.; Radey, Matthew; Hayden, Hillary S.; Held, Kiara G.; Huse, Holly K.; Zurawski, Daniel V.; Brittnacher, Mitchell J.; Manoil, Colin

2015-01-01

ABSTRACT Acinetobacter baumannii is a Gram-negative bacterial pathogen notorious for causing serious nosocomial infections that resist antibiotic therapy. Research to identify factors responsible for the pathogen's success has been limited by the resources available for genome-scale experimental studies. This report describes the development of several such resources for A. baumannii strain AB5075, a recently characterized wound isolate that is multidrug resistant and displays robust virulence in animal models. We report the completion and annotation of the genome sequence, the construction of a comprehensive ordered transposon mutant library, the extension of high-coverage transposon mutant pool sequencing (Tn-seq) to the strain, and the identification of the genes essential for growth on nutrient-rich agar. These resources should facilitate large-scale genetic analysis of virulence, resistance, and other clinically relevant traits that make A. baumannii a formidable public health threat. IMPORTANCE Acinetobacter baumannii is one of six bacterial pathogens primarily responsible for antibiotic-resistant infections that have become the scourge of health care facilities worldwide. Eliminating such infections requires a deeper understanding of the factors that enable the pathogen to persist in hospital environments, establish infections, and resist antibiotics. We present a set of resources that should accelerate genome-scale genetic characterization of these traits for a reference isolate of A. baumannii that is highly virulent and representative of current outbreak strains. PMID:25845845

Multifactorial Likelihood Assessment of BRCA1 and BRCA2 Missense Variants Confirms That BRCA1:c.122A>G(p.His41Arg) Is a Pathogenic Mutation

PubMed Central

Whiley, Phillip J.; Parsons, Michael T.; Leary, Jennifer; Tucker, Kathy; Warwick, Linda; Dopita, Belinda; Thorne, Heather; Lakhani, Sunil R.; Goldgar, David E.; Brown, Melissa A.; Spurdle, Amanda B.

2014-01-01

Rare exonic, non-truncating variants in known cancer susceptibility genes such as BRCA1 and BRCA2 are problematic for genetic counseling and clinical management of relevant families. This study used multifactorial likelihood analysis and/or bioinformatically-directed mRNA assays to assess pathogenicity of 19 BRCA1 or BRCA2 variants identified following patient referral to clinical genetic services. Two variants were considered to be pathogenic (Class 5). BRCA1:c.4484G> C(p.Arg1495Thr) was shown to result in aberrant mRNA transcripts predicted to encode truncated proteins. The BRCA1:c.122A>G(p.His41Arg) RING-domain variant was found from multifactorial likelihood analysis to have a posterior probability of pathogenicity of 0.995, a result consistent with existing protein functional assay data indicating lost BARD1 binding and ubiquitin ligase activity. Of the remaining variants, seven were determined to be not clinically significant (Class 1), nine were likely not pathogenic (Class 2), and one was uncertain (Class 3).These results have implications for genetic counseling and medical management of families carrying these specific variants. They also provide additional multifactorial likelihood variant classifications as reference to evaluate the sensitivity and specificity of bioinformatic prediction tools and/or functional assay data in future studies. PMID:24489791

Molecular Diversity of Anthracnose Pathogen Populations Associated with UK Strawberry Production Suggests Multiple Introductions of Three Different Colletotrichum Species

PubMed Central

Baroncelli, Riccardo; Zapparata, Antonio; Sarrocco, Sabrina; Sukno, Serenella A.; Lane, Charles R.; Thon, Michael R.; Vannacci, Giovanni; Holub, Eric; Sreenivasaprasad, Surapareddy

2015-01-01

Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production. PMID:26086351

Targeted next-generation sequencing makes new molecular diagnoses and expands genotype-phenotype relationship in Ehlers-Danlos syndrome.

PubMed

Weerakkody, Ruwan A; Vandrovcova, Jana; Kanonidou, Christina; Mueller, Michael; Gampawar, Piyush; Ibrahim, Yousef; Norsworthy, Penny; Biggs, Jennifer; Abdullah, Abdulshakur; Ross, David; Black, Holly A; Ferguson, David; Cheshire, Nicholas J; Kazkaz, Hanadi; Grahame, Rodney; Ghali, Neeti; Vandersteen, Anthony; Pope, F Michael; Aitman, Timothy J

2016-11-01

Ehlers-Danlos syndrome (EDS) comprises a group of overlapping hereditary disorders of connective tissue with significant morbidity and mortality, including major vascular complications. We sought to identify the diagnostic utility of a next-generation sequencing (NGS) panel in a mixed EDS cohort. We developed and applied PCR-based NGS assays for targeted, unbiased sequencing of 12 collagen and aortopathy genes to a cohort of 177 unrelated EDS patients. Variants were scored blind to previous genetic testing and then compared with results of previous Sanger sequencing. Twenty-eight pathogenic variants in COL5A1/2, COL3A1, FBN1, and COL1A1 and four likely pathogenic variants in COL1A1, TGFBR1/2, and SMAD3 were identified by the NGS assays. These included all previously detected single-nucleotide and other short pathogenic variants in these genes, and seven newly detected pathogenic or likely pathogenic variants leading to clinically significant diagnostic revisions. Twenty-two variants of uncertain significance were identified, seven of which were in aortopathy genes and required clinical follow-up. Unbiased NGS-based sequencing made new molecular diagnoses outside the expected EDS genotype-phenotype relationship and identified previously undetected clinically actionable variants in aortopathy susceptibility genes. These data may be of value in guiding future clinical pathways for genetic diagnosis in EDS.Genet Med 18 11, 1119-1127.

The Insect Pathogens.

PubMed

Lovett, Brian; St Leger, Raymond J

2017-03-01

Fungi are the most common disease-causing agents of insects; aside from playing a crucial role in natural ecosystems, insect-killing fungi are being used as alternatives to chemical insecticides and as resources for biotechnology and pharmaceuticals. Some common experimentally tractable genera, such as Metarhizium spp., exemplify genetic diversity and dispersal because they contain numerous intraspecific variants with distinct environmental and insect host ranges. The availability of tools for molecular genetics and multiple sequenced genomes has made these fungi ideal experimental models for answering basic questions on the genetic and genomic processes behind adaptive phenotypes. For example, comparative genomics of entomopathogenic fungi has shown they exhibit diverse reproductive modes that often determine rates and patterns of genome evolution and are linked as cause or effect with pathogenic strategies. Fungal-insect pathogens represent lifestyle adaptations that evolved numerous times, and there are significant differences in host range and pathogenic strategies between the major groups. However, typically, spores landing on the cuticle produce appressoria and infection pegs that breach the cuticle using mechanical pressure and cuticle-degrading enzymes. Once inside the insect body cavity, fungal pathogens face a potent and comprehensively studied immune defense by which the host attempts to eliminate or reduce an infection. The Fungal Kingdom stands alone in the range, extent, and complexity of their manipulation of arthropod behavior. In part, this is because most only sporulate on cadavers, so they must ensure the dying host positions itself to allow efficient transmission.

The first step toward genetic selection for host tolerance to infectious pathogens: obtaining the tolerance phenotype through group estimates

PubMed Central

Doeschl-Wilson, Andrea B.; Villanueva, Beatriz; Kyriazakis, Ilias

2012-01-01

Reliable phenotypes are paramount for meaningful quantification of genetic variation and for estimating individual breeding values on which genetic selection is based. In this paper, we assert that genetic improvement of host tolerance to disease, although desirable, may be first of all handicapped by the ability to obtain unbiased tolerance estimates at a phenotypic level. In contrast to resistance, which can be inferred by appropriate measures of within host pathogen burden, tolerance is more difficult to quantify as it refers to change in performance with respect to changes in pathogen burden. For this reason, tolerance phenotypes have only been specified at the level of a group of individuals, where such phenotypes can be estimated using regression analysis. However, few stsudies have raised the potential bias in these estimates resulting from confounding effects between resistance and tolerance. Using a simulation approach, we demonstrate (i) how these group tolerance estimates depend on within group variation and co-variation in resistance, tolerance, and vigor (performance in a pathogen free environment); and (ii) how tolerance estimates are affected by changes in pathogen virulence over the time course of infection and by the timing of measurements. We found that in order to obtain reliable group tolerance estimates, it is important to account for individual variation in vigor, if present, and that all individuals are at the same stage of infection when measurements are taken. The latter requirement makes estimation of tolerance based on cross-sectional field data challenging, as individuals become infected at different time points and the individual onset of infection is unknown. Repeated individual measurements of within host pathogen burden and performance would not only be valuable for inferring the infection status of individuals in field conditions, but would also provide tolerance estimates that capture the entire time course of infection. PMID:23412990

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

Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.

PubMed

Olson, Victoria A; Karem, Kevin L; Smith, Scott K; Hughes, Christine M; Damon, Inger K

2009-04-01

Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.

Genetic diversity, inbreeding and cancer.

PubMed

Ujvari, Beata; Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frédéric; Madsen, Thomas

2018-03-28

Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer. © 2018 The Author(s).

Genetic diversity, inbreeding and cancer

PubMed Central

Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frédéric

2018-01-01

Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer. PMID:29563261

Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis.

PubMed

Cissé, Ousmane H; Ma, Liang; Wei Huang, Da; Khil, Pavel P; Dekker, John P; Kutty, Geetha; Bishop, Lisa; Liu, Yueqin; Deng, Xilong; Hauser, Philippe M; Pagni, Marco; Hirsch, Vanessa; Lempicki, Richard A; Stajich, Jason E; Cuomo, Christina A; Kovacs, Joseph A

2018-05-08

Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro Human Pneumocystis infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of Pneumocystis infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that Pneumocystis species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of Pneumocystis populations during their spread across mammals. IMPORTANCE Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. Pneumocystis , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, Pneumocystis can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different Pneumocystis species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that Pneumocystis may have undergone recent host shifts. The results demonstrate that Pneumocystis strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.

Remote transient Lactobacillus animalis bacteremia causing prosthetic hip joint infection: a case report.

PubMed

Somayaji, R; Lynch, T; Powell, J N; Gregson, D

2016-11-04

Lactobacillus spp. are uncommon pathogens in immunocompetent hosts, and even rarer causes of prosthetic device infections. A case of chronic hip prosthetic joint infection (PJI) caused by L. animalis is described. This occurred 5 years after a transient bacteremia with the same organism. Whole genome sequencing of both isolates proved this PJI infection resulted from this remote bacteremia. We document that prosthetic joint infections may be a consequence of bacteremia as much as 3 years before the onset of symptoms.

Linking genetic and environmental factors in amphibian disease risk

PubMed Central

Savage, Anna E; Becker, Carlos G; Zamudio, Kelly R

2015-01-01

A central question in evolutionary biology is how interactions between organisms and the environment shape genetic differentiation. The pathogen Batrachochytrium dendrobatidis (Bd) has caused variable population declines in the lowland leopard frog (Lithobates yavapaiensis); thus, disease has potentially shaped, or been shaped by, host genetic diversity. Environmental factors can also influence both amphibian immunity and Bd virulence, confounding our ability to assess the genetic effects on disease dynamics. Here, we used genetics, pathogen dynamics, and environmental data to characterize L. yavapaiensis populations, estimate migration, and determine relative contributions of genetic and environmental factors in predicting Bd dynamics. We found that the two uninfected populations belonged to a single genetic deme, whereas each infected population was genetically unique. We detected an outlier locus that deviated from neutral expectations and was significantly correlated with mortality within populations. Across populations, only environmental variables predicted infection intensity, whereas environment and genetics predicted infection prevalence, and genetic diversity alone predicted mortality. At one locality with geothermally elevated water temperatures, migration estimates revealed source–sink dynamics that have likely prevented local adaptation. We conclude that integrating genetic and environmental variation among populations provides a better understanding of Bd spatial epidemiology, generating more effective conservation management strategies for mitigating amphibian declines. PMID:26136822

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

PubMed

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

2017-07-10

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

Species interactions in occurrence data for a community of tick-transmitted pathogens

PubMed Central

Estrada-Peña, Agustín; de la Fuente, José

2016-01-01

Interactions between tick species, their realized range of hosts, the pathogens they carry and transmit, and the geographic distribution of species in the Western Palearctic were determined based on evidence published between 1970–2014. These relationships were linked to remotely sensed features of temperature and vegetation and used to extract the network of interactions among the organisms. The resulting datasets focused on niche overlap among ticks and hosts, species interactions, and the fraction of the environmental niche in which tick-borne pathogens may circulate as a result of interactions and overlapping environmental traits. The resulting datasets provide a valuable resource for researchers interested in tick-borne pathogens, as they conciliate the abiotic and biotic sides of their niche, allowing exploration of the importance of each host species acting as a vertebrate reservoir in the circulation of tick-transmitted pathogens in the environmental niche. PMID:27479213

Aerial Mapping of Forests Affected by Pathogens Using UAVs, Hyperspectral Sensors, and Artificial Intelligence.

PubMed

Sandino, Juan; Pegg, Geoff; Gonzalez, Felipe; Smith, Grant

2018-03-22

The environmental and economic impacts of exotic fungal species on natural and plantation forests have been historically catastrophic. Recorded surveillance and control actions are challenging because they are costly, time-consuming, and hazardous in remote areas. Prolonged periods of testing and observation of site-based tests have limitations in verifying the rapid proliferation of exotic pathogens and deterioration rates in hosts. Recent remote sensing approaches have offered fast, broad-scale, and affordable surveys as well as additional indicators that can complement on-ground tests. This paper proposes a framework that consolidates site-based insights and remote sensing capabilities to detect and segment deteriorations by fungal pathogens in natural and plantation forests. This approach is illustrated with an experimentation case of myrtle rust ( Austropuccinia psidii ) on paperbark tea trees ( Melaleuca quinquenervia ) in New South Wales (NSW), Australia. The method integrates unmanned aerial vehicles (UAVs), hyperspectral image sensors, and data processing algorithms using machine learning. Imagery is acquired using a Headwall Nano-Hyperspec ® camera, orthorectified in Headwall SpectralView ® , and processed in Python programming language using eXtreme Gradient Boosting (XGBoost), Geospatial Data Abstraction Library (GDAL), and Scikit-learn third-party libraries. In total, 11,385 samples were extracted and labelled into five classes: two classes for deterioration status and three classes for background objects. Insights reveal individual detection rates of 95% for healthy trees, 97% for deteriorated trees, and a global multiclass detection rate of 97%. The methodology is versatile to be applied to additional datasets taken with different image sensors, and the processing of large datasets with freeware tools.

Aerial Mapping of Forests Affected by Pathogens Using UAVs, Hyperspectral Sensors, and Artificial Intelligence

PubMed Central

2018-01-01

The environmental and economic impacts of exotic fungal species on natural and plantation forests have been historically catastrophic. Recorded surveillance and control actions are challenging because they are costly, time-consuming, and hazardous in remote areas. Prolonged periods of testing and observation of site-based tests have limitations in verifying the rapid proliferation of exotic pathogens and deterioration rates in hosts. Recent remote sensing approaches have offered fast, broad-scale, and affordable surveys as well as additional indicators that can complement on-ground tests. This paper proposes a framework that consolidates site-based insights and remote sensing capabilities to detect and segment deteriorations by fungal pathogens in natural and plantation forests. This approach is illustrated with an experimentation case of myrtle rust (Austropuccinia psidii) on paperbark tea trees (Melaleuca quinquenervia) in New South Wales (NSW), Australia. The method integrates unmanned aerial vehicles (UAVs), hyperspectral image sensors, and data processing algorithms using machine learning. Imagery is acquired using a Headwall Nano-Hyperspec® camera, orthorectified in Headwall SpectralView®, and processed in Python programming language using eXtreme Gradient Boosting (XGBoost), Geospatial Data Abstraction Library (GDAL), and Scikit-learn third-party libraries. In total, 11,385 samples were extracted and labelled into five classes: two classes for deterioration status and three classes for background objects. Insights reveal individual detection rates of 95% for healthy trees, 97% for deteriorated trees, and a global multiclass detection rate of 97%. The methodology is versatile to be applied to additional datasets taken with different image sensors, and the processing of large datasets with freeware tools. PMID:29565822

New Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) Scheme for Fine-Scale Monitoring and Microevolution-Related Study of Ralstonia pseudosolanacearum Phylotype I Populations

PubMed Central

Guinard, Jérémy; Latreille, Anne; Guérin, Fabien; Poussier, Stéphane

2016-01-01

ABSTRACT Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) is considered one of the most harmful plant diseases in the world. Special attention should be paid to R. pseudosolanacearum phylotype I due to its large host range, its worldwide distribution, and its high evolutionary potential. So far, the molecular epidemiology and population genetics of this bacterium are poorly understood. Until now, the genetic structure of the RSSC has been analyzed on the worldwide and regional scales. Emerging questions regarding evolutionary forces in RSSC adaptation to hosts now require genetic markers that are able to monitor RSSC field populations. In this study, we aimed to evaluate the multilocus variable-number tandem-repeat analysis (MLVA) approach for its ability to discriminate genetically close phylotype I strains and for population genetics studies. We developed a new MLVA scheme (MLVA-7) allowing us to genotype 580 R. pseudosolanacearum phylotype I strains extracted from susceptible and resistant hosts and from different habitats (stem, soil, and rhizosphere). Based on specificity, polymorphism, and the amplification success rate, we selected seven fast-evolving variable-number tandem-repeat (VNTR) markers. The newly developed MLVA-7 scheme showed higher discriminatory power than the previously published MLVA-13 scheme when applied to collections sampled from the same location on different dates and to collections from different locations on very small scales. Our study provides a valuable tool for fine-scale monitoring and microevolution-related study of R. pseudosolanacearum phylotype I populations. IMPORTANCE Understanding the evolutionary dynamics of adaptation of plant pathogens to new hosts or ecological niches has become a key point for the development of innovative disease management strategies, including durable resistance. Whereas the molecular mechanisms underlying virulence or pathogenicity changes have been studied thoroughly, the population genetics of plant pathogen adaptation remains an open, unexplored field, especially for plant-pathogenic bacteria. MLVA has become increasingly popular for epidemiosurveillance and molecular epidemiology studies of plant pathogens. However, this method has been used mostly for genotyping and identification on a regional or global scale. In this study, we developed a new MLVA scheme, targeting phylotype I of the soilborne Ralstonia solanacearum species complex (RSSC), specifically to address the bacterial population genetics on the field scale. Such a MLVA scheme, based on fast-evolving loci, may be a tool of choice for field experimental evolution and spatial genetics studies. PMID:28003195

Point detection of bacterial and viral pathogens using oral samples

NASA Astrophysics Data System (ADS)

Malamud, Daniel

2008-04-01

Oral samples, including saliva, offer an attractive alternative to serum or urine for diagnostic testing. This is particularly true for point-of-use detection systems. The various types of oral samples that have been reported in the literature are presented here along with the wide variety of analytes that have been measured in saliva and other oral samples. The paper focuses on utilizing point-detection of infectious disease agents, and presents work from our group on a rapid test for multiple bacterial and viral pathogens by monitoring a series of targets. It is thus possible in a single oral sample to identify multiple pathogens based on specific antigens, nucleic acids, and host antibodies to those pathogens. The value of such a technology for detecting agents of bioterrorism at remote sites is discussed.

Mechanisms of Antibiotic Resistance

PubMed Central

Munita, Jose M.; Arias, Cesar A.

2015-01-01

Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

Retracing the Evolutionary Path that Led to Flea-borne Transmission of Yersinia pestis

PubMed Central

Sun, Yi-Cheng; Jarrett, Clayton O.; Bosio, Christopher F.; Hinnebusch, B. Joseph

2014-01-01

Summary Yersinia pestis is an arthropod-borne bacterial pathogen that evolved recently from Yersinia pseudotuberculosis, an enteric pathogen transmitted via the fecal-oral route. This radical ecological transition can be attributed to a few discrete genetic changes from a still-extant recent ancestor, thus providing a tractable case study in pathogen evolution and emergence. Here, we determined the precise genetic and mechanistic basis of the evolutionary adaptation of Y. pestis to flea-borne transmission. Remarkably, only four minor changes in the bacterial progenitor, representing one gene gain and three gene losses, enabled transmission by flea vectors. All three loss-of-function mutations enhanced c-di-GMP-mediated bacterial biofilm formation in the flea foregut that greatly increased transmissibility. Our results suggest a step-wise evolutionary model in which Y. pestis emerged as a flea-borne clone, with each genetic change incrementally reinforcing the transmission cycle. The model conforms well to the ecological theory of adaptive radiation. PMID:24832452

Retracing the evolutionary path that led to flea-borne transmission of Yersinia pestis.

PubMed

Sun, Yi-Cheng; Jarrett, Clayton O; Bosio, Christopher F; Hinnebusch, B Joseph

2014-05-14

Yersinia pestis is an arthropod-borne bacterial pathogen that evolved recently from Yersinia pseudotuberculosis, an enteric pathogen transmitted via the fecal-oral route. This radical ecological transition can be attributed to a few discrete genetic changes from a still-extant recent ancestor, thus providing a tractable case study in pathogen evolution and emergence. Here, we determined the genetic and mechanistic basis of the evolutionary adaptation of Y. pestis to flea-borne transmission. Remarkably, only four minor changes in the bacterial progenitor, representing one gene gain and three gene losses, enabled transmission by flea vectors. All three loss-of-function mutations enhanced cyclic-di-GMP-mediated bacterial biofilm formation in the flea foregut, which greatly increased transmissibility. Our results suggest a step-wise evolutionary model in which Y. pestis emerged as a flea-borne clone, with each genetic change incrementally reinforcing the transmission cycle. The model conforms well to the ecological theory of adaptive radiation. Copyright © 2014 Elsevier Inc. All rights reserved.

Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

PubMed

Lee, Soo Chan; Li, Alicia; Calo, Silvia; Inoue, Makoto; Tonthat, Nam K; Bain, Judith M; Louw, Johanna; Shinohara, Mari L; Erwig, Lars P; Schumacher, Maria A; Ko, Dennis C; Heitman, Joseph

2015-09-01

Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-locked phenotype indicating that calcineurin governs the dimorphic transition. Genetic analysis in this study reveals that two calcineurin A catalytic subunits (out of three) are functionally diverged. Homology modeling illustrates modes of resistance resulting from amino substitutions in the interface between each calcineurin subunit and the inhibitory drugs. In addition, we show how the dimorphic transition orchestrated by calcineurin programs different outcomes during host-pathogen interactions. For example, when macrophages phagocytose Mucor yeast, subsequent phagosomal maturation occurs, indicating host cells respond appropriately to control the pathogen. On the other hand, upon phagocytosis of spores, macrophages fail to form mature phagosomes. Cytokine production from immune cells differs following exposure to yeast versus spores (which germinate into hyphae). Thus, the morphogenic transition can be targeted as an efficient treatment option against Mucor infection. In addition, genetic analysis (including gene disruption and mutational studies) further strengthens the understanding of calcineurin and provides a foundation to develop antifungal agents targeting calcineurin to deploy against Mucor and other pathogenic fungi. © 2015 John Wiley & Sons Ltd.

Strategies for new and improved vaccines against ticks and tick-borne diseases.

PubMed

de la Fuente, J; Kopáček, P; Lew-Tabor, A; Maritz-Olivier, C

2016-12-01

Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. © 2016 John Wiley & Sons Ltd.

Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species.

PubMed

Zhong, Zhenhui; Norvienyeku, Justice; Chen, Meilian; Bao, Jiandong; Lin, Lianyu; Chen, Liqiong; Lin, Yahong; Wu, Xiaoxian; Cai, Zena; Zhang, Qi; Lin, Xiaoye; Hong, Yonghe; Huang, Jun; Xu, Linghong; Zhang, Honghong; Chen, Long; Tang, Wei; Zheng, Huakun; Chen, Xiaofeng; Wang, Yanli; Lian, Bi; Zhang, Liangsheng; Tang, Haibao; Lu, Guodong; Ebbole, Daniel J; Wang, Baohua; Wang, Zonghua

2016-05-06

One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants.

Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species

PubMed Central

Zhong, Zhenhui; Norvienyeku, Justice; Chen, Meilian; Bao, Jiandong; Lin, Lianyu; Chen, Liqiong; Lin, Yahong; Wu, Xiaoxian; Cai, Zena; Zhang, Qi; Lin, Xiaoye; Hong, Yonghe; Huang, Jun; Xu, Linghong; Zhang, Honghong; Chen, Long; Tang, Wei; Zheng, Huakun; Chen, Xiaofeng; Wang, Yanli; Lian, Bi; Zhang, Liangsheng; Tang, Haibao; Lu, Guodong; Ebbole, Daniel J.; Wang, Baohua; Wang, Zonghua

2016-01-01

One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants. PMID:27151494

Mixtures of genetically modified wheat lines outperform monocultures.

PubMed

Zeller, Simon L; Kalinina, Olena; Flynn, Dan F B; Schmid, Bernhard

2012-09-01

Biodiversity research shows that diverse plant communities are more stable and productive than monocultures. Similarly, populations in which genotypes with different pathogen resistance are mixed may have lower pathogen levels and thus higher productivity than genetically uniform populations. We used genetically modified (GM) wheat as a model system to test this prediction, because it allowed us to use genotypes that differed only in the trait pathogen resistance but were otherwise identical. We grew three such genotypes or lines in monocultures or two-line mixtures. Phenotypic measurements were taken at the level of individual plants and of entire plots (population level). We found that resistance to mildew increased with both GM richness (0, 1, or 2 Pm3 transgenes with different resistance specificities per plot) and GM concentration (0%, 50%, or 100% of all plants in a plot with a Pm3 transgene). Plots with two transgenes had 34.6% less mildew infection and as a consequence 7.3% higher seed yield than plots with one transgene. We conclude that combining genetic modification with mixed cropping techniques could be a promising approach to increase sustainability and productivity in agricultural systems, as the fitness cost of stacking transgenes within individuals may thus be avoided.

Host shifts result in parallel genetic changes when viruses evolve in closely related species

PubMed Central

Day, Jonathan P.; Smith, Sophia C. L.; Houslay, Thomas M.; Tagliaferri, Lucia

2018-01-01

Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases. They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species. To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes. We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species. When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related. This suggests that when a virus adapts to one host it might also become better adapted to closely related host species. This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease. PMID:29649296

Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

PubMed Central

Hamede, Rodrigo K.; Pearse, Anne-Maree; Swift, Kate; Barmuta, Leon A.; Murchison, Elizabeth P.; Jones, Menna E.

2015-01-01

Tasmanian devil facial tumour disease (DFTD) is a clonally transmissible cancer threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Over the 18 years since DFTD was first observed, distinct genetic and karyotypic sublineages have evolved. In this longitudinal study, we investigate the associations between tumour karyotype, epidemic patterns and host demographic response to the disease. Reduced host population effects and low DFTD infection rates were associated with high prevalence of tetraploid tumours. Subsequent replacement by a diploid variant of DFTD coincided with a rapid increase in disease prevalence, population decline and reduced mean age of the population. Our results suggest a role for tumour genetics in DFTD transmission dynamics and epidemic outcome. Future research, for this and other highly pathogenic emerging infectious diseases, should focus on understanding the evolution of host and pathogen genotypes, their effects on susceptibility and tolerance to infection, and their implications for designing novel genetic management strategies. This study provides evidence for a rapid localized lineage replacement occurring within a transmissible cancer epidemic and highlights the possibility that distinct DFTD genetic lineages may harbour traits that influence pathogen fitness. PMID:26336167

Genetic Analysis of Vibrio parahaemolyticus O3:K6 Strains That Have Been Isolated in Mexico Since 1998

PubMed Central

Licea-Navarro, Alexei Fedorovish; Revilla-Castellanos, Valeria Jeanette; Wong-Chang, Irma; González-Sánchez, Ricardo

2017-01-01

Vibrio parahaemolyticus is an important human pathogen that has been isolated worldwide from clinical cases, most of which have been associated with seafood consumption. Environmental and clinical toxigenic strains of V. parahaemolyticus that were isolated in Mexico from 1998 to 2012, including those from the only outbreak that has been reported in this country, were characterized genetically to assess the presence of the O3:K6 pandemic clone, and their genetic relationship to strains that are related to the pandemic clonal complex (CC3). Pathogenic tdh+ and tdh+/trh+ strains were analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Also, the entire genome of a Mexican O3:K6 strain was sequenced. Most of the strains were tdh/ORF8-positive and corresponded to the O3:K6 serotype. By PFGE and MLST, there was very close genetic relationship between ORF8/O3:K6 strains, and very high genetic diversities from non-pandemic strains. The genetic relationship is very close among O3:K6 strains that were isolated in Mexico and sequences that were available for strains in the CC3, based on the PubMLST database. The whole-genome sequence of CICESE-170 strain had high similarity with that of the reference RIMD 2210633 strain, and harbored 7 pathogenicity islands, including the 4 that denote O3:K6 pandemic strains. These results indicate that pandemic strains that have been isolated in Mexico show very close genetic relationship among them and with those isolated worldwide. PMID:28099500

Rise of the microbes

PubMed Central

Mahan, Michael J.; Kubicek-Sutherland, Jessica Z.; Heithoff, Douglas M.

2013-01-01

Infectious diseases continue to plague the modern world. In the evolutionary arms race of pathogen emergence, the rules of engagement appear to have suddenly changed. Human activities have collided with nature to hasten the emergence of more potent pathogens from natural microbial populations. This is evident in recent infectious disease outbreaks, the events that led to their origin, and lessons learned: influenza (2009), meningitis (Africa, 2009), cholera (Haiti, 2010), E. coli (Germany, 2011) and Salmonella (USA, 2012). Developing a comprehensive control plan requires an understanding of the genetics, epidemiology and evolution of emergent pathogens for which humans have little or no pre-existing immunity. As we plot our next move, nature’s genetic lottery continues, providing the fuel to transform the most unlikely infectious disease scenarios into reality. PMID:23334178

Kinetoplastids: related protozoan pathogens, different diseases

PubMed Central

Stuart, Ken; Brun, Reto; Croft, Simon; Fairlamb, Alan; Gürtler, Ricardo E.; McKerrow, Jim; Reed, Steve; Tarleton, Rick

2008-01-01

Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these “neglected diseases” are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better. PMID:18382742

Inter-individual variability and genetic influences on cytokine responses against bacterial and fungal pathogens

PubMed Central

Li, Yang; Oosting, Marije; Deelen, Patrick; Ricaño-Ponce, Isis; Smeekens, Sanne; Jaeger, Martin; Matzaraki, Vasiliki; Swertz, Morris A.; Xavier, Ramnik J.; Franke, Lude; Wijmenga, Cisca; Joosten, Leo A.B.; Kumar, Vinod; Netea, Mihai G.

2016-01-01

Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens, and to determine the impact of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort within the Human Functional Genomics Study (www.humanfunctionalgenomics.org), obtained over three different years. By comparing bacteria- and fungi-induced cytokine profiles, we show that most cytokine responses are organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide SNP genotypes with cytokine abundance and identified six cytokine QTLs. Among them, a cytokine QTL at NAA35-GOLM1 locus markedly modulates IL-6 production in response to multiple pathogens, and associated with susceptibility to candidemia. Furthermore, the cytokine QTLs we identified are enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens. PMID:27376574

Impact of Vector Dispersal and Host-Plant Fidelity on the Dissemination of an Emerging Plant Pathogen

PubMed Central

Johannesen, Jes; Foissac, Xavier; Kehrli, Patrik; Maixner, Michael

2012-01-01

Dissemination of vector-transmitted pathogens depend on the survival and dispersal of the vector and the vector's ability to transmit the pathogen, while the host range of vector and pathogen determine the breath of transmission possibilities. In this study, we address how the interaction between dispersal and plant fidelities of a pathogen (stolbur phytoplasma tuf-a) and its vector (Hyalesthes obsoletus: Cixiidae) affect the emergence of the pathogen. Using genetic markers, we analysed the geographic origin and range expansion of both organisms in Western Europe and, specifically, whether the pathogen's dissemination in the northern range is caused by resident vectors widening their host-plant use from field bindweed to stinging nettle, and subsequent host specialisation. We found evidence for common origins of pathogen and vector south of the European Alps. Genetic patterns in vector populations show signals of secondary range expansion in Western Europe leading to dissemination of tuf-a pathogens, which might be newly acquired and of hybrid origin. Hence, the emergence of stolbur tuf-a in the northern range was explained by secondary immigration of vectors carrying stinging nettle-specialised tuf-a, not by widening the host-plant spectrum of resident vectors with pathogen transmission from field bindweed to stinging nettle nor by primary co-migration from the resident vector's historical area of origin. The introduction of tuf-a to stinging nettle in the northern range was therefore independent of vector's host-plant specialisation but the rapid pathogen dissemination depended on the vector's host shift, whereas the general dissemination elsewhere was linked to plant specialisation of the pathogen but not of the vector. PMID:23284774

Impact of vector dispersal and host-plant fidelity on the dissemination of an emerging plant pathogen.

PubMed

Johannesen, Jes; Foissac, Xavier; Kehrli, Patrik; Maixner, Michael

2012-01-01

Dissemination of vector-transmitted pathogens depend on the survival and dispersal of the vector and the vector's ability to transmit the pathogen, while the host range of vector and pathogen determine the breath of transmission possibilities. In this study, we address how the interaction between dispersal and plant fidelities of a pathogen (stolbur phytoplasma tuf-a) and its vector (Hyalesthes obsoletus: Cixiidae) affect the emergence of the pathogen. Using genetic markers, we analysed the geographic origin and range expansion of both organisms in Western Europe and, specifically, whether the pathogen's dissemination in the northern range is caused by resident vectors widening their host-plant use from field bindweed to stinging nettle, and subsequent host specialisation. We found evidence for common origins of pathogen and vector south of the European Alps. Genetic patterns in vector populations show signals of secondary range expansion in Western Europe leading to dissemination of tuf-a pathogens, which might be newly acquired and of hybrid origin. Hence, the emergence of stolbur tuf-a in the northern range was explained by secondary immigration of vectors carrying stinging nettle-specialised tuf-a, not by widening the host-plant spectrum of resident vectors with pathogen transmission from field bindweed to stinging nettle nor by primary co-migration from the resident vector's historical area of origin. The introduction of tuf-a to stinging nettle in the northern range was therefore independent of vector's host-plant specialisation but the rapid pathogen dissemination depended on the vector's host shift, whereas the general dissemination elsewhere was linked to plant specialisation of the pathogen but not of the vector.

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

PubMed

Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M; Papatheodorou, Efstathios; Ware, James S; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R; Crawford, Jackie; Love, Donald R; Pua, Chee J; Soh, Bee Y; Bhalshankar, Jaydutt D; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G; van der Werf, Christian; Wijeyeratne, Yanushi D; Mellor, Greg; Till, Jan; Cohen, Marta C; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A M; Cook, Stuart A; Bezzina, Connie R; Sheppard, Mary N; Behr, Elijah R

2017-05-02

Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10 -5 ). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Population Structure in Naegleria fowleri as Revealed by Microsatellite Markers

PubMed Central

Coupat-Goutaland, Bénédicte; Régoudis, Estelle; Besseyrias, Matthieu; Mularoni, Angélique; Binet, Marie; Herbelin, Pascaline; Pélandakis, Michel

2016-01-01

Naegleria sp. is a free living amoeba belonging to the Heterolobosea class. Over 40 species of Naegleria were identified and recovered worldwide in different habitats such as swimming pools, freshwater lakes, soil or dust. Among them, N. fowleri, is a human pathogen responsible for primary amoeboic meningoencephalitis (PAM). Around 300 cases were reported in 40 years worldwide but PAM is a fatal disease of the central nervous system with only 5% survival of infected patients. Since both pathogenic and non pathogenic species were encountered in the environment, detection and dispersal mode are crucial points in the fight against this pathogenic agent. Previous studies on identification and genotyping of N. fowleri strains were focused on RAPD analysis and on ITS sequencing and identified 5 variants: euro-american, south pacific, widespread, cattenom and chooz. Microsatellites are powerful markers in population genetics with broad spectrum of applications (such as paternity test, fingerprinting, genetic mapping or genetic structure analysis). They are characterized by a high degree of length polymorphism. The aim of this study was to genotype N. fowleri strains using microsatellites markers in order to track this population and to better understand its evolution. Six microsatellite loci and 47 strains from different geographical origins were used for this analysis. The microsatellite markers revealed a level of discrimination higher than any other marker used until now, enabling the identification of seven genetic groups, included in the five main genetic groups based on the previous RAPD and ITS analyses. This analysis also allowed us to go further in identifying private alleles highlighting intra-group variability. A better identification of the N. fowleri isolates could be done with this type of analysis and could allow a better tracking of the clinical and environmental N. fowleri strains. PMID:27035434

Population Structure in Naegleria fowleri as Revealed by Microsatellite Markers.

PubMed

Coupat-Goutaland, Bénédicte; Régoudis, Estelle; Besseyrias, Matthieu; Mularoni, Angélique; Binet, Marie; Herbelin, Pascaline; Pélandakis, Michel

2016-01-01

Naegleria sp. is a free living amoeba belonging to the Heterolobosea class. Over 40 species of Naegleria were identified and recovered worldwide in different habitats such as swimming pools, freshwater lakes, soil or dust. Among them, N. fowleri, is a human pathogen responsible for primary amoeboic meningoencephalitis (PAM). Around 300 cases were reported in 40 years worldwide but PAM is a fatal disease of the central nervous system with only 5% survival of infected patients. Since both pathogenic and non pathogenic species were encountered in the environment, detection and dispersal mode are crucial points in the fight against this pathogenic agent. Previous studies on identification and genotyping of N. fowleri strains were focused on RAPD analysis and on ITS sequencing and identified 5 variants: euro-american, south pacific, widespread, cattenom and chooz. Microsatellites are powerful markers in population genetics with broad spectrum of applications (such as paternity test, fingerprinting, genetic mapping or genetic structure analysis). They are characterized by a high degree of length polymorphism. The aim of this study was to genotype N. fowleri strains using microsatellites markers in order to track this population and to better understand its evolution. Six microsatellite loci and 47 strains from different geographical origins were used for this analysis. The microsatellite markers revealed a level of discrimination higher than any other marker used until now, enabling the identification of seven genetic groups, included in the five main genetic groups based on the previous RAPD and ITS analyses. This analysis also allowed us to go further in identifying private alleles highlighting intra-group variability. A better identification of the N. fowleri isolates could be done with this type of analysis and could allow a better tracking of the clinical and environmental N. fowleri strains.

Genetics Home Reference: ankylosing spondylitis

MedlinePlus

... SUSCEPTIBILITY TO, 1 Sources for This Page Brown MA. Breakthroughs in genetic studies of ankylosing spondylitis. Rheumatology ( ... 10.1002/art.23177. Citation on PubMed Khan MA. HLA-B27 and its pathogenic role. J Clin ...

The genetics of pre-eclampsia and other hypertensive disorders of pregnancy

PubMed Central

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

Hypertension is the most frequent medical complication occurring during pregnancy. In this chapter, we aim to address the genetic contribution to these disorders, with specific focus on pre-eclampsia. The pathogenic mechanisms underlying pre-eclampsia remain to be elucidated; however, immune maladaptation, inadequate placental development and trophoblast invasion, placental ischaemia, oxidative stress and thrombosis are all thought to represent key factors in the development of disease. Furthermore, all of these components have genetic factors that may be involved in the pathogenic changes occurring. The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis. Interactions between fetal and maternal genotypes, the effect of environmental factors, and epistasis will also be considered. PMID:21429808

Genetic variability of Brazilian isolates of Alternaria alternata detected by AFLP and RAPD techniques

PubMed Central

Dini-Andreote, Francisco; Pietrobon, Vivian Cristina; Andreote, Fernando Dini; Romão, Aline Silva; Spósito, Marcel Bellato; Araújo, Welington Luiz

2009-01-01

The Alternaria brown spot (ABS) is a disease caused in tangerine plants and its hybrids by the fungus Alternaria alternata f. sp. citri which has been found in Brazil since 2001. Due to the recent occurrence in Brazilian orchards, the epidemiology and genetic variability of this pathogen is still an issue to be addressed. Here it is presented a survey about the genetic variability of this fungus by the characterization of twenty four pathogenic isolates of A. alternata f. sp. citri from citrus plants and four endophytic isolates from mango (one Alternaria tenuissima and three Alternaria arborescens). The application of two molecular markers Random Amplified Polymorphic DNA (RAPD) and Amplified Fragment Length Polymorphism (AFLP) had revealed the isolates clustering in distinct groups when fingerprintings were analyzed by Principal Components Analysis (PCA). Despite the better assessment of the genetic variability through the AFLP, significant modifications in clusters components were not observed, and only slight shifts in the positioning of isolates LRS 39/3 and 25M were observed in PCA plots. Furthermore, in both analyses, only the isolates from lemon plants revealed to be clustered, differently from the absence of clustering for other hosts or plant tissues. Summarizing, both RAPD and AFLP analyses were both efficient to detect the genetic variability within the population of the pathogenic fungus Alternaria spp., supplying information on the genetic variability of this species as a basis for further studies aiming the disease control. PMID:24031413

Chapter VIII. Contributions of propagation techniques and genetic modification to breeding - genetic engineering for disease resistance

USDA-ARS?s Scientific Manuscript database

Genetic engineering offers an opportunity to develop flower bulb crops with resistance to fungal, viral, and bacterial pathogens. Several of the flower bulb crops, Lilium spp., Gladiolus, Zantedeschia, Muscari, Hyacinthus, Narcissus, Ornithogalum, Iris, and Alstroemeria, have been transformed with t...

Benefits of Genomic Insights and CRISPR-Cas Signatures to Monitor Potential Pathogens across Drinking Water Production and Distribution Systems

PubMed Central

Zhang, Ya; Kitajima, Masaaki; Whittle, Andrew J.; Liu, Wen-Tso

2017-01-01

The occurrence of pathogenic bacteria in drinking water distribution systems (DWDSs) is a major health concern, and our current understanding is mostly related to pathogenic species such as Legionella pneumophila and Mycobacterium avium but not to bacterial species closely related to them. In this study, genomic-based approaches were used to characterize pathogen-related species in relation to their abundance, diversity, potential pathogenicity, genetic exchange, and distribution across an urban drinking water system. Nine draft genomes recovered from 10 metagenomes were identified as Legionella (4 draft genomes), Mycobacterium (3 draft genomes), Parachlamydia (1 draft genome), and Leptospira (1 draft genome). The pathogenicity potential of these genomes was examined by the presence/absence of virulence machinery, including genes belonging to Type III, IV, and VII secretion systems and their effectors. Several virulence factors known to pathogenic species were detected with these retrieved draft genomes except the Leptospira-related genome. Identical clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) genetic signatures were observed in two draft genomes recovered at different stages of the studied system, suggesting that the spacers in CRISPR-Cas could potentially be used as a biomarker in the monitoring of Legionella related strains at an evolutionary scale of several years across different drinking water production and distribution systems. Overall, metagenomics approach was an effective and complementary tool of culturing techniques to gain insights into the pathogenic characteristics and the CRISPR-Cas signatures of pathogen-related species in DWDSs. PMID:29097994

Genetic variation affecting host-parasite interactions: different genes affect different aspects of sigma virus replication and transmission in Drosophila melanogaster.

PubMed

Bangham, Jenny; Kim, Kang-Wook; Webster, Claire L; Jiggins, Francis M

2008-04-01

In natural populations, genetic variation affects resistance to disease. Knowing how much variation exists, and understanding the genetic architecture of this variation, is important for medicine, for agriculture, and for understanding evolutionary processes. To investigate the extent and nature of genetic variation affecting resistance to pathogens, we are studying a tractable model system: Drosophila melanogaster and its natural pathogen the vertically transmitted sigma virus. We show that considerable genetic variation affects transmission of the virus from parent to offspring. However, maternal and paternal transmission of the virus is affected by different genes. Maternal transmission is a simple Mendelian trait: most of the genetic variation is explained by a polymorphism in ref(2)P, a gene already well known to affect resistance to sigma. In contrast, there is considerable genetic variation in paternal transmission that cannot be explained by ref(2)P and is caused by other loci on chromosome 2. Furthermore, we found no genetic correlation between paternal transmission of the virus and resistance to infection by the sigma virus following injection. This suggests that different loci affect viral replication and paternal transmission.

Advances in control of wheat rusts

USDA-ARS?s Scientific Manuscript database

This chapter provides a summary of recent advances in wheat rust research. Although the emphasis is on recent developments, some historical context is provided. Critical concepts in studying the wheat rusts are pathogen and host genetics, host-pathogen interactions, epidemiology and management strat...

Population Genomics of Fungal and Oomycete Pathogens.

PubMed

Grünwald, Niklaus J; McDonald, Bruce A; Milgroom, Michael G

2016-08-04

We are entering a new era in plant pathology in which whole-genome sequences of many individuals of a pathogen species are becoming readily available. Population genomics aims to discover genetic mechanisms underlying phenotypes associated with adaptive traits such as pathogenicity, virulence, fungicide resistance, and host specialization, as genome sequences or large numbers of single nucleotide polymorphisms become readily available from multiple individuals of the same species. This emerging field encompasses detailed genetic analyses of natural populations, comparative genomic analyses of closely related species, identification of genes under selection, and linkage analyses involving association studies in natural populations or segregating populations resulting from crosses. The era of pathogen population genomics will provide new opportunities and challenges, requiring new computational and analytical tools. This review focuses on conceptual and methodological issues as well as the approaches to answering questions in population genomics. The major steps start with defining relevant biological and evolutionary questions, followed by sampling, genotyping, and phenotyping, and ending in analytical methods and interpretations. We provide examples of recent applications of population genomics to fungal and oomycete plant pathogens.

Novel Disease Susceptibility Factors for Fungal Necrotrophic Pathogens in Arabidopsis

PubMed Central

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

2015-01-01

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

RNAi in Arthropods: Insight into the Machinery and Applications for Understanding the Pathogen-Vector Interface

PubMed Central

Barnard, Annette-Christi; Nijhof, Ard M.; Fick, Wilma; Stutzer, Christian; Maritz-Olivier, Christine

2012-01-01

The availability of genome sequencing data in combination with knowledge of expressed genes via transcriptome and proteome data has greatly advanced our understanding of arthropod vectors of disease. Not only have we gained insight into vector biology, but also into their respective vector-pathogen interactions. By combining the strengths of postgenomic databases and reverse genetic approaches such as RNAi, the numbers of available drug and vaccine targets, as well as number of transgenes for subsequent transgenic or paratransgenic approaches, have expanded. These are now paving the way for in-field control strategies of vectors and their pathogens. Basic scientific questions, such as understanding the basic components of the vector RNAi machinery, is vital, as this allows for the transfer of basic RNAi machinery components into RNAi-deficient vectors, thereby expanding the genetic toolbox of these RNAi-deficient vectors and pathogens. In this review, we focus on the current knowledge of arthropod vector RNAi machinery and the impact of RNAi on understanding vector biology and vector-pathogen interactions for which vector genomic data is available on VectorBase. PMID:24705082

How Often Do They Have Sex? A Comparative Analysis of the Population Structure of Seven Eukaryotic Microbial Pathogens

PubMed Central

Tomasini, Nicolás; Lauthier, Juan José; Ayala, Francisco José; Tibayrenc, Michel; Diosque, Patricio

2014-01-01

The model of predominant clonal evolution (PCE) proposed for micropathogens does not state that genetic exchange is totally absent, but rather, that it is too rare to break the prevalent PCE pattern. However, the actual impact of this “residual” genetic exchange should be evaluated. Multilocus Sequence Typing (MLST) is an excellent tool to explore the problem. Here, we compared online available MLST datasets for seven eukaryotic microbial pathogens: Trypanosoma cruzi, the Fusarium solani complex, Aspergillus fumigatus, Blastocystis subtype 3, the Leishmania donovani complex, Candida albicans and Candida glabrata. We first analyzed phylogenetic relationships among genotypes within each dataset. Then, we examined different measures of branch support and incongruence among loci as signs of genetic structure and levels of past recombination. The analyses allow us to identify three types of genetic structure. The first was characterized by trees with well-supported branches and low levels of incongruence suggesting well-structured populations and PCE. This was the case for the T. cruzi and F. solani datasets. The second genetic structure, represented by Blastocystis spp., A. fumigatus and the L. donovani complex datasets, showed trees with weakly-supported branches but low levels of incongruence among loci, whereby genetic structuration was not clearly defined by MLST. Finally, trees showing weakly-supported branches and high levels of incongruence among loci were observed for Candida species, suggesting that genetic exchange has a higher evolutionary impact in these mainly clonal yeast species. Furthermore, simulations showed that MLST may fail to show right clustering in population datasets even in the absence of genetic exchange. In conclusion, these results make it possible to infer variable impacts of genetic exchange in populations of predominantly clonal micro-pathogens. Moreover, our results reveal different problems of MLST to determine the genetic structure in these organisms that should be considered. PMID:25054834

Comparative Genomics of Oral Isolates of Streptococcus mutans by in silico Genome Subtraction Does Not Reveal Accessory DNA Associated with Severe Early Childhood Caries

PubMed Central

Argimón, Silvia; Konganti, Kranti; Chen, Hao; Alekseyenko, Alexander V.; Brown, Stuart; Caufield, Page W.

2014-01-01

Comparative genomics is a popular method for the identification of microbial virulence determinants, especially since the sequencing of a large number of whole bacterial genomes from pathogenic and non-pathogenic strains has become relatively inexpensive. The bioinformatics pipelines for comparative genomics usually include gene prediction and annotation and can require significant computer power. To circumvent this, we developed a rapid method for genome-scale in silico subtractive hybridization, based on blastn and independent of feature identification and annotation. Whole genome comparisons by in silico genome subtraction were performed to identify genetic loci specific to Streptococcus mutans strains associated with severe early childhood caries (S-ECC), compared to strains isolated from caries-free (CF) children. The genome similarity of the 20 S. mutans strains included in this study, calculated by Simrank k-mer sharing, ranged from 79.5 to 90.9%, confirming this is a genetically heterogeneous group of strains. We identified strain-specific genetic elements in 19 strains, with sizes ranging from 200 bp to 39 kb. These elements contained protein-coding regions with functions mostly associated with mobile DNA. We did not, however, identify any genetic loci consistently associated with dental caries, i.e., shared by all the S-ECC strains and absent in the CF strains. Conversely, we did not identify any genetic loci specific with the healthy group. Comparison of previously published genomes from pathogenic and carriage strains of Neisseria meningitidis with our in silico genome subtraction yielded the same set of genes specific to the pathogenic strains, thus validating our method. Our results suggest that S. mutans strains derived from caries active or caries free dentitions cannot be differentiated based on the presence or absence of specific genetic elements. Our in silico genome subtraction method is available as the Microbial Genome Comparison (MGC) tool, with a user-friendly JAVA graphical interface. PMID:24291226

Actionable exomic incidental findings in 6503 participants: challenges of variant classification

PubMed Central

Amendola, Laura M.; Dorschner, Michael O.; Robertson, Peggy D.; Salama, Joseph S.; Hart, Ragan; Shirts, Brian H.; Murray, Mitzi L.; Tokita, Mari J.; Gallego, Carlos J.; Kim, Daniel Seung; Bennett, James T.; Crosslin, David R.; Ranchalis, Jane; Jones, Kelly L.; Rosenthal, Elisabeth A.; Jarvik, Ella R.; Itsara, Andy; Turner, Emily H.; Herman, Daniel S.; Schleit, Jennifer; Burt, Amber; Jamal, Seema M.; Abrudan, Jenica L.; Johnson, Andrew D.; Conlin, Laura K.; Dulik, Matthew C.; Santani, Avni; Metterville, Danielle R.; Kelly, Melissa; Foreman, Ann Katherine M.; Lee, Kristy; Taylor, Kent D.; Guo, Xiuqing; Crooks, Kristy; Kiedrowski, Lesli A.; Raffel, Leslie J.; Gordon, Ora; Machini, Kalotina; Desnick, Robert J.; Biesecker, Leslie G.; Lubitz, Steven A.; Mulchandani, Surabhi; Cooper, Greg M.; Joffe, Steven; Richards, C. Sue; Yang, Yaoping; Rotter, Jerome I.; Rich, Stephen S.; O’Donnell, Christopher J.; Berg, Jonathan S.; Spinner, Nancy B.; Evans, James P.; Fullerton, Stephanie M.; Leppig, Kathleen A.; Bennett, Robin L.; Bird, Thomas; Sybert, Virginia P.; Grady, William M.; Tabor, Holly K.; Kim, Jerry H.; Bamshad, Michael J.; Wilfond, Benjamin; Motulsky, Arno G.; Scott, C. Ronald; Pritchard, Colin C.; Walsh, Tom D.; Burke, Wylie; Raskind, Wendy H.; Byers, Peter; Hisama, Fuki M.; Rehm, Heidi; Nickerson, Debbie A.; Jarvik, Gail P.

2015-01-01

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. PMID:25637381

A whole genome Bayesian scan for adaptive genetic divergence in West African cattle

PubMed Central

2009-01-01

Background The recent settlement of cattle in West Africa after several waves of migration from remote centres of domestication has imposed dramatic changes in their environmental conditions, in particular through exposure to new pathogens. West African cattle populations thus represent an appealing model to unravel the genome response to adaptation to tropical conditions. The purpose of this study was to identify footprints of adaptive selection at the whole genome level in a newly collected data set comprising 36,320 SNPs genotyped in 9 West African cattle populations. Results After a detailed analysis of population structure, we performed a scan for SNP differentiation via a previously proposed Bayesian procedure including extensions to improve the detection of loci under selection. Based on these results we identified 53 genomic regions and 42 strong candidate genes. Their physiological functions were mainly related to immune response (MHC region which was found under strong balancing selection, CD79A, CXCR4, DLK1, RFX3, SEMA4A, TICAM1 and TRIM21), nervous system (NEUROD6, OLFM2, MAGI1, SEMA4A and HTR4) and skin and hair properties (EDNRB, TRSP1 and KRTAP8-1). Conclusion The main possible underlying selective pressures may be related to climatic conditions but also to the host response to pathogens such as Trypanosoma(sp). Overall, these results might open the way towards the identification of important variants involved in adaptation to tropical conditions and in particular to resistance to tropical infectious diseases. PMID:19930592

Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar.

PubMed

Jain, Abhinav; Gandhi, Shrey; Koshy, Remya; Scaria, Vinod

2018-03-20

Incidental findings in genomic data have been studied in great detail in the recent years, especially from population-scale data sets. However, little is known about the frequency of such findings in ethnic groups, specifically the Middle East, which were not previously covered in global sequencing studies. The availability of whole exome and genome data sets for a highly consanguineous Arab population from Qatar motivated us to explore the incidental findings in this population-scale data. The sequence data of 1005 Qatari individuals were systematically analyzed for incidental genetic variants in the 59 genes suggested by the American College of Medical Genetics and Genomics. We identified four genetic variants which were pathogenic or likely pathogenic. These variants occurred in six individuals, suggesting a frequency of 0.59% in the population, much lesser than that previously reported from European and African populations. Our analysis identified a variant in RYR1 gene associated with Malignant Hyperthermia that has significantly higher frequency in the population compared to global frequencies. Evaluation of the allele frequencies of these variants suggested enrichment in sub-populations, especially in individuals of Sub-Saharan African ancestry. The present study thereby provides the information on pathogenicity and frequency, which could aid in genomic medicine. To the best of our knowledge, this is the first comprehensive analysis of incidental genetic findings in any Arab population and suggests ethnic differences in incidental findings.

A Framework for Engineering Stress Resilient Plants Using Genetic Feedback Control and Regulatory Network Rewiring.

PubMed

Foo, Mathias; Gherman, Iulia; Zhang, Peijun; Bates, Declan G; Denby, Katherine J

2018-05-23

Crop disease leads to significant waste worldwide, both pre- and postharvest, with subsequent economic and sustainability consequences. Disease outcome is determined both by the plants' response to the pathogen and by the ability of the pathogen to suppress defense responses and manipulate the plant to enhance colonization. The defense response of a plant is characterized by significant transcriptional reprogramming mediated by underlying gene regulatory networks, and components of these networks are often targeted by attacking pathogens. Here, using gene expression data from Botrytis cinerea-infected Arabidopsis plants, we develop a systematic approach for mitigating the effects of pathogen-induced network perturbations, using the tools of synthetic biology. We employ network inference and system identification techniques to build an accurate model of an Arabidopsis defense subnetwork that contains key genes determining susceptibility of the plant to the pathogen attack. Once validated against time-series data, we use this model to design and test perturbation mitigation strategies based on the use of genetic feedback control. We show how a synthetic feedback controller can be designed to attenuate the effect of external perturbations on the transcription factor CHE in our subnetwork. We investigate and compare two approaches for implementing such a controller biologically-direct implementation of the genetic feedback controller, and rewiring the regulatory regions of multiple genes-to achieve the network motif required to implement the controller. Our results highlight the potential of combining feedback control theory with synthetic biology for engineering plants with enhanced resilience to environmental stress.

Fungal life-styles and ecosystem dynamics: biological aspects of plant pathogens, plant endophytes and saprophytes

USGS Publications Warehouse

Rodriguez, R.J.; Redman, R.S.

1997-01-01

This chapter discusses various biochemical, genetic, ecological, and evolutionary aspects of fungi that express either symbiotic or saprophytic life-styles. An enormous pool of potential pathogens exists in both agricultural and natural ecosystems, and virtually all plant species are susceptible to one or more fungal pathogens. Fungal pathogens have the potential to impact on the genetic structure of populations of individual plant species, the composition of plant communities and the process of plant succession. Endophytic fungi exist for at least part of their life cycles within the tissues of a plant host. This group of fungi is distinguished from plant pathogens because they do not elicit significant disease symptoms. However, endophytes do maintain the genetic and biochemical mechanisms required for infection and colonization of plant hosts. Fungi that obtain chemical nutrients from dead organic matter are known as saprophytes and are critical to the dynamics and resilience of ecosystems. There are two modes of saprophytic growth: one in which biomolecules that are amenable to transport across cell walls and membranes are directly absorbed, and another in which fungi must actively convert complex biopolymers into subunit forms amenable to transportation into cells. Regardless of life-style, fungi employ similar biochemical mechanisms for the acquisition and conversion of nutrients into complex biomolecules that are necessary for vegetative growth, production and dissemination of progeny, organismal competition, and survival during periods of nutrient deprivation or environmental inclemency.

Differences in pathogenicity of A/Duck/Vietnam/201/05 H5N1 highly pathogenic avian influenza virus reassortants in ducks

USDA-ARS?s Scientific Manuscript database

In order to understand which viral genes contribute to the high virulence of A/Dk/Vietnam/201/05 H5N1 highly pathogenic avian influenza (HPAI) virus in ducks, we used reverse genetics to generate single-gene reassortant viruses with genes from A/Ck/Indonesia/7/03, a virus that produces mild disease ...

The pathogenesis of H7N8 low and highly pathogenic avian influenza viruses from the United States 2016 outbreak in chickens, turkeys and mallards

USDA-ARS?s Scientific Manuscript database

In January 2016, a combined outbreak of highly pathogenic (HP) avian influenza virus (AIV) and low pathogenicity (LP) AIV occurred in commercial turkeys in the state of Indiana, United States. Genetically, the viruses were highly similar, belonged to the North American wild bird lineage, and had not...

Within-host competitive exclusion among species of the anther smut pathogen

PubMed Central

Gold, Alexander; Giraud, Tatiana; Hood, Michael E

2009-01-01

Background Host individuals represent an arena in which pathogens compete for resources and transmission opportunities, with major implications for the evolution of virulence and the structure of populations. Studies to date have focused on competitive interactions within pathogen species, and the level of antagonism tends to increase with the genetic distance between competitors. Anther-smut fungi, in the genus Microbotryum, have emerged as a tractable model for within-host competition. Here, using two pathogen species that are frequently found in sympatry, we investigated whether the antagonism seen among genotypes of the same species cascades up to influence competition among pathogen species. Results Sequential inoculation of hosts showed that a resident infection most often excludes a challenging pathogen genotype, which is consistent with prior studies. However, the challenging pathogen was significantly more likely to invade the already-infected host if the resident infection was a conspecific genotype compared to challenges involving a closely related species. Moreover, when inter-specific co-infection occurred, the pathogens were highly segregated within the host, in contrast to intra-specific co-infection. Conclusion We show evidence that competitive exclusion during infection can be greater among closely related pathogen species than among genotypes within species. This pattern follows from prior studies demonstrating that genetic distance and antagonistic interactions are positively correlated in Microbotryum. Fungal vegetative incompatibility is a likely mechanism of direct competitive interference, and has been shown in some fungi to be effective both within and across species boundaries. For systems where related pathogen species frequently co-occur in the same host populations, these competitive dynamics may substantially impact the spatial segregation of pathogen species. PMID:19422703

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 ...

Diagnosis and Management of Hereditary Phaeochromocytoma and Paraganglioma.

PubMed

Lalloo, Fiona

2016-01-01

About 30% of phaeochromocytomas or paragangliomas are genetic. Whilst some individuals will have clinical features or a family history of inherited cancer syndrome such as neurofibromatosis type 1 (NF1) or multiple endocrine neoplasia 2 (MEN2), the majority will present as an isolated case. To date, 14 genes have been described in which pathogenic mutations have been demonstrated to cause paraganglioma or phaeochromocytoma . Many cases with a pathogenic mutation may be at risk of developing further tumours. Therefore, identification of genetic cases is important in the long-term management of these individuals, ensuring that they are entered into a surveillance programme. Mutation testing also facilitates cascade testing within the family, allowing identification of other at-risk individuals. Many algorithms have been described to facilitate cost-effective genetic testing sequentially of these genes, with phenotypically driven pathways. New genetic technologies including next-generation sequencing and whole-exome sequencing will allow much quicker, cheaper and extensive testing of individuals in whom a genetic aetiology is suspected.

Aggregation of population‐based genetic variation over protein domain homologues and its potential use in genetic diagnostics

PubMed Central

Wiel, Laurens; Venselaar, Hanka; Veltman, Joris A.; Vriend, Gert

2017-01-01

Abstract Whole exomes of patients with a genetic disorder are nowadays routinely sequenced but interpretation of the identified genetic variants remains a major challenge. The increased availability of population‐based human genetic variation has given rise to measures of genetic tolerance that have been used, for example, to predict disease‐causing genes in neurodevelopmental disorders. Here, we investigated whether combining variant information from homologous protein domains can improve variant interpretation. For this purpose, we developed a framework that maps population variation and known pathogenic mutations onto 2,750 “meta‐domains.” These meta‐domains consist of 30,853 homologous Pfam protein domain instances that cover 36% of all human protein coding sequences. We find that genetic tolerance is consistent across protein domain homologues, and that patterns of genetic tolerance faithfully mimic patterns of evolutionary conservation. Furthermore, for a significant fraction (68%) of the meta‐domains high‐frequency population variation re‐occurs at the same positions across domain homologues more often than expected. In addition, we observe that the presence of pathogenic missense variants at an aligned homologous domain position is often paired with the absence of population variation and vice versa. The use of these meta‐domains can improve the interpretation of genetic variation. PMID:28815929

Additive genetic variation in resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus iniae and S. agalactiae capsular type Ib: is genetic resistance correlated?

USDA-ARS?s Scientific Manuscript database

Streptococcus (S.) iniae and S. agalactiae are both economically important Gram positive bacterial pathogens affecting the globally farmed tilapia (Oreochromis spp.). Historically control of these bacteria in tilapia culture has included biosecurity, therapeutants and vaccination strategies. Genet...

Maize chiA as a Potential Genetic Marker for Stenocarpella maydis Ear Rot Resistance

USDA-ARS?s Scientific Manuscript database

Stenocarpella maydis (Diplodia maydis) is the most prevalent ear rot pathogen in nearly all countries where maize is produced. The genetic basis of plant resistance to S. maydis appears to rely on multiple genetic factors, none of which are known. We previously reported that S. maydis secretes a p...

Rapid diagnosis of avian influenza virus in wild birds: Use of a portable rRT-PCR and freeze-dried reagents in the field

USGS Publications Warehouse

Takekawa, John Y.; Hill, N.J.; Schultz, A.K.; Iverson, S.A.; Cardona, C.J.; Boyce, W.M.; Dudley, J.P.

2011-01-01

Wild birds have been implicated in the spread of highly pathogenic avian influenza (HPAI) of the H5N1 subtype, prompting surveillance along migratory flyways. Sampling of wild birds for avian influenza virus (AIV) is often conducted in remote regions, but results are often delayed because of the need to transport samples to a laboratory equipped for molecular testing. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) is a molecular technique that offers one of the most accurate and sensitive methods for diagnosis of AIV. The previously strict lab protocols needed for rRT-PCR are now being adapted for the field. Development of freeze-dried (lyophilized) reagents that do not require cold chain, with sensitivity at the level of wet reagents has brought on-site remote testing to a practical goal. Here we present a method for the rapid diagnosis of AIV in wild birds using an rRT-PCR unit (Ruggedized Advanced Pathogen Identification Device or RAPID, Idaho Technologies, Salt Lake City, UT) that employs lyophilized reagents (Influenza A Target 1 Taqman; ASAY-ASY-0109, Idaho Technologies). The reagents contain all of the necessary components for testing at appropriate concentrations in a single tube: primers, probes, enzymes, buffers and internal positive controls, eliminating errors associated with improper storage or handling of wet reagents. The portable unit performs a screen for Influenza A by targeting the matrix gene and yields results in 2-3 hours. Genetic subtyping is also possible with H5 and H7 primer sets that target the hemagglutinin gene. The system is suitable for use on cloacal and oropharyngeal samples collected from wild birds, as demonstrated here on the migratory shorebird species, the western sandpiper (Calidrus mauri) captured in Northern California. Animal handling followed protocols approved by the Animal Care and Use Committee of the U.S. Geological Survey Western Ecological Research Center and permits of the U.S. Geological Survey Bird Banding Laboratory. The primary advantage of this technique is to expedite diagnosis of wild birds, increasing the chances of containing an outbreak in a remote location. On-site diagnosis would also prove useful for identifying and studying infected individuals in wild populations. The opportunity to collect information on host biology (immunological and physiological response to infection) and spatial ecology (migratory performance of infected birds) will provide insights into the extent to which wild birds can act as vectors for AIV over long distances.

Rapid Diagnosis of Avian Influenza Virus in Wild Birds: Use of a Portable rRT-PCR and Freeze-dried Reagents in the Field

PubMed Central

Takekawa, John Y.; Hill, Nichola J.; Schultz, Annie K.; Iverson, Samuel A.; Cardona, Carol J.; Boyce, Walter M.; Dudley, Joseph P.

2011-01-01

Wild birds have been implicated in the spread of highly pathogenic avian influenza (HPAI) of the H5N1 subtype, prompting surveillance along migratory flyways. Sampling of wild birds for avian influenza virus (AIV) is often conducted in remote regions, but results are often delayed because of the need to transport samples to a laboratory equipped for molecular testing. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) is a molecular technique that offers one of the most accurate and sensitive methods for diagnosis of AIV. The previously strict lab protocols needed for rRT-PCR are now being adapted for the field. Development of freeze-dried (lyophilized) reagents that do not require cold chain, with sensitivity at the level of wet reagents has brought on-site remote testing to a practical goal. Here we present a method for the rapid diagnosis of AIV in wild birds using an rRT-PCR unit (Ruggedized Advanced Pathogen Identification Device or RAPID, Idaho Technologies, Salt Lake City, UT) that employs lyophilized reagents (Influenza A Target 1 Taqman; ASAY-ASY-0109, Idaho Technologies). The reagents contain all of the necessary components for testing at appropriate concentrations in a single tube: primers, probes, enzymes, buffers and internal positive controls, eliminating errors associated with improper storage or handling of wet reagents. The portable unit performs a screen for Influenza A by targeting the matrix gene and yields results in 2-3 hours. Genetic subtyping is also possible with H5 and H7 primer sets that target the hemagglutinin gene. The system is suitable for use on cloacal and oropharyngeal samples collected from wild birds, as demonstrated here on the migratory shorebird species, the western sandpiper (Calidrus mauri) captured in Northern California. Animal handling followed protocols approved by the Animal Care and Use Committee of the U.S. Geological Survey Western Ecological Research Center and permits of the U.S. Geological Survey Bird Banding Laboratory. The primary advantage of this technique is to expedite diagnosis of wild birds, increasing the chances of containing an outbreak in a remote location. On-site diagnosis would also prove useful for identifying and studying infected individuals in wild populations. The opportunity to collect information on host biology (immunological and physiological response to infection) and spatial ecology (migratory performance of infected birds) will provide insights into the extent to which wild birds can act as vectors for AIV over long distances. PMID:21847073

Inheritance and variability of tolerance to Verticillium dahliae Kleb amoung geographically remote F1-F2 hybrids of Gossypium hirsutum L.

USDA-ARS?s Scientific Manuscript database

One of the most important problems for cotton breeding in Uzbekistan is development of Verticillium dahliae tolerant varieties. One approach is to utilize ecologically remote intraspecific and interspecific hybridization with local commercial cultivars. To this end, we have conducted genetically b...

Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?

PubMed Central

Macias, Vanessa M.; Ohm, Johanna R.; Rasgon, Jason L.

2017-01-01

Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease. PMID:28869513

A replicative plasmid vector allows efficient complementation of pathogenic Leptospira strains.

PubMed

Pappas, Christopher J; Benaroudj, Nadia; Picardeau, Mathieu

2015-05-01

Leptospirosis, an emerging zoonotic disease, remains poorly understood because of a lack of genetic manipulation tools available for pathogenic leptospires. Current genetic manipulation techniques include insertion of DNA by random transposon mutagenesis and homologous recombination via suicide vectors. This study describes the construction of a shuttle vector, pMaORI, that replicates within saprophytic, intermediate, and pathogenic leptospires. The shuttle vector was constructed by the insertion of a 2.9-kb DNA segment including the parA, parB, and rep genes into pMAT, a plasmid that cannot replicate in Leptospira spp. and contains a backbone consisting of an aadA cassette, ori R6K, and oriT RK2/RP4. The inserted DNA segment was isolated from a 52-kb region within Leptospira mayottensis strain 200901116 that is not found in the closely related strain L. mayottensis 200901122. Because of the size of this region and the presence of bacteriophage-like proteins, it is possible that this region is a result of a phage-related genomic island. The stability of the pMaORI plasmid within pathogenic strains was tested by passaging cultures 10 times without selection and confirming the presence of pMaORI. Concordantly, we report the use of trans complementation in the pathogen Leptospira interrogans. Transformation of a pMaORI vector carrying a functional copy of the perR gene in a null mutant background restores the expression of PerR and susceptibility to hydrogen peroxide comparable to that of wild-type cells. In conclusion, we demonstrate the replication of a stable plasmid vector in a large panel of Leptospira strains, including pathogens. The shuttle vector described will expand our ability to perform genetic manipulation of Leptospira spp. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Dynamic genetic conservation in the presence of invasive insect and pathogen threats to forest tree species of the United States

Treesearch

J.L. Koch; R.A. Sniezko

2017-01-01

Ex-situ genetic conservation focused on collection and storage of seed can play an important role in conserving the genetic diversity of species under grave threat by biotic organisms or a changing climate. However, ex-situ genetic conservation is primarily a static activity and does not allow for evolution of the species under a continuing,...

Disposable and removable nucleic acid extraction and purification cartridges for automated flow-through systems

DOEpatents

Regan, John Frederick

2014-09-09

Removable cartridges are used on automated flow-through systems for the purpose of extracting and purifying genetic material from complex matrices. Different types of cartridges are paired with specific automated protocols to concentrate, extract, and purifying pathogenic or human genetic material. Their flow-through nature allows large quantities sample to be processed. Matrices may be filtered using size exclusion and/or affinity filters to concentrate the pathogen of interest. Lysed material is ultimately passed through a filter to remove the insoluble material before the soluble genetic material is delivered past a silica-like membrane that binds the genetic material, where it is washed, dried, and eluted. Cartridges are inserted into the housing areas of flow-through automated instruments, which are equipped with sensors to ensure proper placement and usage of the cartridges. Properly inserted cartridges create fluid- and air-tight seals with the flow lines of an automated instrument.

Community acquired pneumonia: genetic variants influencing systemic inflammation.

PubMed

Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

2014-01-01

The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

The importance of molecular analyses for understanding the genetic diversity of Histoplasma capsulatum: an overview.

PubMed

Vite-Garín, Tania; Estrada-Bárcenas, Daniel Alfonso; Cifuentes, Joaquín; Taylor, Maria Lucia

2014-01-01

Advances in the classification of the human pathogen Histoplasma capsulatum (H. capsulatum) (ascomycete) are sustained by the results of several genetic analyses that support the high diversity of this dimorphic fungus. The present mini-review highlights the great genetic plasticity of H. capsulatum. Important records with different molecular tools, mainly single- or multi-locus sequence analyses developed with this fungus, are discussed. Recent phylogenetic data with a multi-locus sequence analysis using 5 polymorphic loci support a new clade and/or phylogenetic species of H. capsulatum for the Americas, which was associated with fungal isolates obtained from the migratory bat Tadarida brasiliensis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol.

PubMed

Meric-Bernstam, F; Brusco, L; Daniels, M; Wathoo, C; Bailey, A M; Strong, L; Shaw, K; Lu, K; Qi, Y; Zhao, H; Lara-Guerra, H; Litton, J; Arun, B; Eterovic, A K; Aytac, U; Routbort, M; Subbiah, V; Janku, F; Davies, M A; Kopetz, S; Mendelsohn, J; Mills, G B; Chen, K

2016-05-01

Next-generation sequencing in cancer research may reveal germline variants of clinical significance. We report patient preferences for return of results and the prevalence of incidental pathogenic germline variants (PGVs). Targeted exome sequencing of 202 genes was carried out in 1000 advanced cancers using tumor and normal DNA in a research laboratory. Pathogenic variants in 18 genes, recommended for return by The American College of Medical Genetics and Genomics, as well as PALB2, were considered actionable. Patient preferences of return of incidental germline results were collected. Return of results was initiated with genetic counseling and repeat CLIA testing. Of the 1000 patients who underwent sequencing, 43 had likely PGVs: APC (1), BRCA1 (11), BRCA2 (10), TP53 (10), MSH2 (1), MSH6 (4), PALB2 (2), PTEN (2), TSC2 (1), and RB1 (1). Twenty (47%) of 43 variants were previously known based on clinical genetic testing. Of the 1167 patients who consented for a germline testing protocol, 1157 (99%) desired to be informed of incidental results. Twenty-three previously unrecognized mutations identified in the research environment were confirmed with an orthogonal CLIA platform. All patients approached decided to proceed with formal genetic counseling; in all cases where formal genetic testing was carried out, the germline variant of concern validated with clinical genetic testing. In this series, 2.3% patients had previously unrecognized pathogenic germline mutations in 19 cancer-related genes. Thus, genomic sequencing must be accompanied by a plan for return of germline results, in partnership with genetic counseling. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Evolution of Drosophila resistance against different pathogens and infection routes entails no detectable maintenance costs.

PubMed

Faria, Vítor G; Martins, Nelson E; Paulo, Tânia; Teixeira, Luís; Sucena, Élio; Magalhães, Sara

2015-11-01

Pathogens exert a strong selective pressure on hosts, entailing host adaptation to infection. This adaptation often affects negatively other fitness-related traits. Such trade-offs may underlie the maintenance of genetic diversity for pathogen resistance. Trade-offs can be tested with experimental evolution of host populations adapting to parasites, using two approaches: (1) measuring changes in immunocompetence in relaxed-selection lines and (2) comparing life-history traits of evolved and control lines in pathogen-free environments. Here, we used both approaches to examine trade-offs in Drosophila melanogaster populations evolving for over 30 generations under infection with Drosophila C Virus or the bacterium Pseudomonas entomophila, the latter through different routes. We find that resistance is maintained after up to 30 generations of relaxed selection. Moreover, no differences in several classical life-history traits between control and evolved populations were found in pathogen-free environments, even under stresses such as desiccation, nutrient limitation, and high densities. Hence, we did not detect any maintenance costs associated with resistance to pathogens. We hypothesize that extremely high selection pressures commonly used lead to the disproportionate expression of costs relative to their actual occurrence in natural systems. Still, the maintenance of genetic variation for pathogen resistance calls for an explanation. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

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

PubMed Central

2014-01-01

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

Analyses between Reproductive Behavior, Genetic Diversity and Pythium Responsiveness in Zingiber spp. Reveal an Adaptive Significance for Hemiclonality

PubMed Central

Thomas, Geethu E.; Geetha, Kiran A.; Augustine, Lesly; Mamiyil, Sabu; Thomas, George

2016-01-01

Mode of reproduction is generally considered to have long-range evolutionary implications on population survival. Because sexual reproduction produces genetically diverse genotypes, this mode of reproduction is predicted to positively influence the success potential of offspring in evolutionary arms race with parasites (Red queen) whereas, without segregation and recombination, the obligate asexual multiplication may push a species into extinction due to the steady accumulation of deleterious mutations (Muller’s ratchet). However, the extent of linearity between reproductive strategies, genetic diversity and population fitness, and the contributions of different breeding strategies to population fitness are yet to be understood clearly. Genus Zingiber belonging to the pan-tropic family Zingiberaceae represents a good system to study contributions of different breeding behavior on genetic diversity and population fitness, as this genus comprises species with contrasting breeding systems. In this study, we analyzed breeding behavior, amplified fragment length polymorphism diversity and response to the soft-rot pathogen Pythium aphanidermatum in 18 natural populations of three wild Zingiber spp.: Z. neesanum, Z. nimmonii, and Z. zerumbet, together with the obligately asexual cultivated congener, ginger (Z. officinale). Ginger showed an exceptionally narrow genetic base, and adding to this, all the tested cultivars were uniformly susceptible to soft-rot. Concordant with the postulates of Muller’s ratchet, the background selection may be continuously pushing ginger into the ancestral state, rendering it inefficient in host-pathogen coevolution. Z. neesanum and Z. nimmonii populations were sexual and genetically diverse; however, contrary to Red Queen expectations, the populations were highly susceptible to soft-rot. Z. zerumbet showed a hemiclonal breeding behavior. The populations inhabiting forest understory were large and continuous, sexual and genetically diverse, but were susceptible, whereas populations inhabiting the revenue land were fragmented and monoclonal, but were resistant. It may be possible that, when genetic recombination becomes at a premium due to the genetic constraints imparted by habitat fragmentation or pathogen pressure, Z. zerumbet PMID:28066470

New Suppressive System with a Novel Antibiotic Conprimycin

USDA-ARS?s Scientific Manuscript database

Crops lack genetic resistance to most necrotrophic pathogens. To compensate for this disadvantage, plants recruit antagonistic members of the soil microbiome to defend their roots against pathogens and other pests. The best examples of this microbe-based defense of roots are observed in disease-supp...

P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster

USDA-ARS?s Scientific Manuscript database

Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect transmitted infectious diseases. The fact that many viruses carry...

First report of an Armillaria root disease pathogen, Armillaria gallica, associated with several new hosts in Hawaii

Treesearch

M.-S. Kim; J. W. Hanna; N. B. Klopfenstein

2010-01-01

The loss and decline of native tree species caused by invasive plant pathogens is a major threat to the endangered endemic forests of the Hawaiian Islands (3). Thus, it is critical to characterize existing pathogens to evaluate potential invasiveness. In August 2005, rhizomorphs and mycelial bark fans of genet HI-4 were collected from dead/declining, mature trees of...

Analysis of Genome Plasticity in Pathogenic and Commensal Escherichia coli Isolates by Use of DNA Arrays

PubMed Central

Dobrindt, Ulrich; Agerer, Franziska; Michaelis, Kai; Janka, Andreas; Buchrieser, Carmen; Samuelson, Martin; Svanborg, Catharina; Gottschalk, Gerhard; Karch, Helge; Hacker, Jörg

2003-01-01

Genomes of prokaryotes differ significantly in size and DNA composition. Escherichia coli is considered a model organism to analyze the processes involved in bacterial genome evolution, as the species comprises numerous pathogenic and commensal variants. Pathogenic and nonpathogenic E. coli strains differ in the presence and absence of additional DNA elements contributing to specific virulence traits and also in the presence and absence of additional genetic information. To analyze the genetic diversity of pathogenic and commensal E. coli isolates, a whole-genome approach was applied. Using DNA arrays, the presence of all translatable open reading frames (ORFs) of nonpathogenic E. coli K-12 strain MG1655 was investigated in 26 E. coli isolates, including various extraintestinal and intestinal pathogenic E. coli isolates, 3 pathogenicity island deletion mutants, and commensal and laboratory strains. Additionally, the presence of virulence-associated genes of E. coli was determined using a DNA “pathoarray” developed in our laboratory. The frequency and distributional pattern of genomic variations vary widely in different E. coli strains. Up to 10% of the E. coli K-12-specific ORFs were not detectable in the genomes of the different strains. DNA sequences described for extraintestinal or intestinal pathogenic E. coli are more frequently detectable in isolates of the same origin than in other pathotypes. Several genes coding for virulence or fitness factors are also present in commensal E. coli isolates. Based on these results, the conserved E. coli core genome is estimated to consist of at least 3,100 translatable ORFs. The absence of K-12-specific ORFs was detectable in all chromosomal regions. These data demonstrate the great genome heterogeneity and genetic diversity among E. coli strains and underline the fact that both the acquisition and deletion of DNA elements are important processes involved in the evolution of prokaryotes. PMID:12618447

New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID).

PubMed

Van Gijn, Marielle E; Ceccherini, Isabella; Shinar, Yael; Carbo, Ellen C; Slofstra, Mariska; Arostegui, Juan I; Sarrabay, Guillaume; Rowczenio, Dorota; Omoyımnı, Ebun; Balci-Peynircioglu, Banu; Hoffman, Hal M; Milhavet, Florian; Swertz, Morris A; Touitou, Isabelle

2018-03-29

Hereditary recurrent fevers (HRFs) are rare inflammatory diseases sharing similar clinical symptoms and effectively treated with anti-inflammatory biological drugs. Accurate diagnosis of HRF relies heavily on genetic testing. This study aimed to obtain an experts' consensus on the clinical significance of gene variants in four well-known HRF genes: MEFV , TNFRSF1A , NLRP3 and MVK . We configured a MOLGENIS web platform to share and analyse pathogenicity classifications of the variants and to manage a consensus-based classification process. Four experts in HRF genetics submitted independent classifications of 858 variants. Classifications were driven to consensus by recruiting four more expert opinions and by targeting discordant classifications in five iterative rounds. Consensus classification was reached for 804/858 variants (94%). None of the unsolved variants (6%) remained with opposite classifications (eg, pathogenic vs benign). New mutational hotspots were found in all genes. We noted a lower pathogenic variant load and a higher fraction of variants with unknown or unsolved clinical significance in the MEFV gene. Applying a consensus-driven process on the pathogenicity assessment of experts yielded rapid classification of almost all variants of four HRF genes. The high-throughput database will profoundly assist clinicians and geneticists in the diagnosis of HRFs. The configured MOLGENIS platform and consensus evolution protocol are usable for assembly of other variant pathogenicity databases. The MOLGENIS software is available for reuse at http://github.com/molgenis/molgenis; the specific HRF configuration is available at http://molgenis.org/said/. The HRF pathogenicity classifications will be published on the INFEVERS database at https://fmf.igh.cnrs.fr/ISSAID/infevers/. © 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.

ClinGen Pathogenicity Calculator: a configurable system for assessing pathogenicity of genetic variants.

PubMed

Patel, Ronak Y; Shah, Neethu; Jackson, Andrew R; Ghosh, Rajarshi; Pawliczek, Piotr; Paithankar, Sameer; Baker, Aaron; Riehle, Kevin; Chen, Hailin; Milosavljevic, Sofia; Bizon, Chris; Rynearson, Shawn; Nelson, Tristan; Jarvik, Gail P; Rehm, Heidi L; Harrison, Steven M; Azzariti, Danielle; Powell, Bradford; Babb, Larry; Plon, Sharon E; Milosavljevic, Aleksandar

2017-01-12

The success of the clinical use of sequencing based tests (from single gene to genomes) depends on the accuracy and consistency of variant interpretation. Aiming to improve the interpretation process through practice guidelines, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) have published standards and guidelines for the interpretation of sequence variants. However, manual application of the guidelines is tedious and prone to human error. Web-based tools and software systems may not only address this problem but also document reasoning and supporting evidence, thus enabling transparency of evidence-based reasoning and resolution of discordant interpretations. In this report, we describe the design, implementation, and initial testing of the Clinical Genome Resource (ClinGen) Pathogenicity Calculator, a configurable system and web service for the assessment of pathogenicity of Mendelian germline sequence variants. The system allows users to enter the applicable ACMG/AMP-style evidence tags for a specific allele with links to supporting data for each tag and generate guideline-based pathogenicity assessment for the allele. Through automation and comprehensive documentation of evidence codes, the system facilitates more accurate application of the ACMG/AMP guidelines, improves standardization in variant classification, and facilitates collaborative resolution of discordances. The rules of reasoning are configurable with gene-specific or disease-specific guideline variations (e.g. cardiomyopathy-specific frequency thresholds and functional assays). The software is modular, equipped with robust application program interfaces (APIs), and available under a free open source license and as a cloud-hosted web service, thus facilitating both stand-alone use and integration with existing variant curation and interpretation systems. The Pathogenicity Calculator is accessible at http://calculator.clinicalgenome.org . By enabling evidence-based reasoning about the pathogenicity of genetic variants and by documenting supporting evidence, the Calculator contributes toward the creation of a knowledge commons and more accurate interpretation of sequence variants in research and clinical care.

Disease resistance in Atlantic salmon (Salmo salar): coinfection of the intracellular bacterial pathogen Piscirickettsia salmonis and the sea louse Caligus rogercresseyi.

PubMed

Lhorente, Jean Paul; Gallardo, José A; Villanueva, Beatriz; Carabaño, María J; Neira, Roberto

2014-01-01

Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h2SI = 0.23 ± 0.07; h2LC = 0.17 ± 0.08; h2HC = 0.24 ± 0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99 ± 0.01) but not between the single and coinfection treatments (rg SI-LC = -0.14 ± 0.33; rg SI-HC = 0.32 ± 0.34). C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation.

Molecular basis of recognition between phytophthora pathogens and their hosts.

PubMed

Tyler, Brett M

2002-01-01

Recognition is the earliest step in any direct plant-microbe interaction. Recognition between Phytophthora pathogens, which are oomycetes, phylogenetically distinct from fungi, has been studied at two levels. Recognition of the host by the pathogen has focused on recognition of chemical, electrical, and physical features of plant roots by zoospores. Both host-specific factors such as isoflavones, and host-nonspecific factors such as amino acids, calcium, and electrical fields, influence zoospore taxis, encystment, cyst germination, and hyphal chemotropism in guiding the pathogen to potential infection sites. Recognition of the pathogen by the host defense machinery has been analyzed using biochemical and genetic approaches. Biochemical approaches have identified chemical elicitors of host defense responses, and in some cases, their cognate receptors from the host. Some elicitors, such as glucans and fatty acids, have broad host ranges, whereas others such as elicitins have narrow host ranges. Most elicitors identified appear to contribute primarily to basic or nonhost resistance. Genetic analysis has identified host resistance (R) genes and pathogen avirulence (Avr) genes that interact in a gene-for-gene manner. One Phytophthora Avr gene, Avr1b from P. sojae, has been cloned and characterized. It encodes a secreted elicitor that triggers a system-wide defense response in soybean plants carrying the cognate R gene, Rps1b.

Genomic diversity of bacteriophages infecting the fish pathogen Flavobacterium psychrophilum.

PubMed

Castillo, Daniel; Middelboe, Mathias

2016-12-01

Bacteriophages infecting the fish pathogen Flavobacterium psychrophilum can potentially be used to prevent and control outbreaks of this bacterium in salmonid aquaculture. However, the application of bacteriophages in disease control requires detailed knowledge on their genetic composition. To explore the diversity of F. pyschrophilum bacteriophages, we have analyzed the complete genome sequences of 17 phages isolated from two distant geographic areas (Denmark and Chile), including the previously characterized temperate bacteriophage 6H. Phage genome size ranged from 39 302 to 89 010 bp with a G+C content of 27%-32%. None of the bacteriophages isolated in Denmark contained genes associated with lysogeny, whereas the Chilean isolates were all putative temperate phages and similar to bacteriophage 6H. Comparative genome analysis showed that phages grouped in three different genetic clusters based on genetic composition and gene content, indicating a limited genetic diversity of F. psychrophilum-specific bacteriophages. However, amino acid sequence dissimilarity (25%) was found in putative structural proteins, which could be related to the host specificity determinants. This study represents the first analysis of genomic diversity and composition among bacteriophages infecting the fish pathogen F. psychrophilum and discusses the implications for the application of phages in disease control. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Host-pathogen evolutionary signatures reveal dynamics and future invasions of vampire bat rabies.

PubMed

Streicker, Daniel G; Winternitz, Jamie C; Satterfield, Dara A; Condori-Condori, Rene Edgar; Broos, Alice; Tello, Carlos; Recuenco, Sergio; Velasco-Villa, Andrés; Altizer, Sonia; Valderrama, William

2016-09-27

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.

Inbreeding and disease resistance in a social insect: effects of heterozygosity on immunocompetence in the termite Zootermopsis angusticollis

PubMed Central

Calleri, Daniel V; McGrail Reid, Ellen; Rosengaus, Rebeca B; Vargo, Edward L; Traniello, James F.A

2006-01-01

Recent research has shown that low genetic variation in individuals can increase susceptibility to infection and group living may exacerbate pathogen transmission. In the eusocial diploid termites, cycles of outbreeding and inbreeding characterizing basal species can reduce genetic variation within nestmates during the life of a colony, but the relationship of genetic heterogeneity to disease resistance is poorly understood. Here we show that, one generation of inbreeding differentially affects the survivorship of isolated and grouped termites (Zootermopsis angusticollis) depending on the nature of immune challenge and treatment. Inbred and outbred isolated and grouped termites inoculated with a bacterial pathogen, exposed to a low dose of fungal pathogen or challenged with an implanted nylon monofilament had similar levels of immune defence. However, inbred grouped termites exposed to a relatively high concentration of fungal conidia had significantly greater mortality than outbred grouped termites. Inbred termites also had significantly higher cuticular microbial loads, presumably due to less effective grooming by nestmates. Genetic analyses showed that inbreeding significantly reduced heterozygosity and allelic diversity. Decreased heterozygosity thus appeared to increase disease susceptibility by affecting social behaviour or some other group-level process influencing infection control rather than affecting individual immune physiology. PMID:17002949

Genetic diversity of Histoplasma and Sporothrix complexes based on sequences of their ITS1-5.8S-ITS2 regions from the BOLD System.

PubMed

Estrada-Bárcenas, Daniel Alfonso; Vite-Garín, Tania; Navarro-Barranco, Hortensia; de la Torre-Arciniega, Raúl; Pérez-Mejía, Amelia; Rodríguez-Arellanes, Gabriela; Ramirez, Jose Antonio; Humberto Sahaza, Jorge; Taylor, Maria Lucia; Toriello, Conchita

2014-01-01

High sensitivity and specificity of molecular biology techniques have proven usefulness for the detection, identification and typing of different pathogens. The ITS (Internal Transcribed Spacer) regions of the ribosomal DNA are highly conserved non-coding regions, and have been widely used in different studies including the determination of the genetic diversity of human fungal pathogens. This article wants to contribute to the understanding of the intra- and interspecific genetic diversity of isolates of the Histoplasma capsulatum and Sporothrix schenckii species complexes by an analysis of the available sequences of the ITS regions from different sequence databases. ITS1-5.8S-ITS2 sequences of each fungus, either deposited in GenBank, or from our research groups (registered in the Fungi Barcode of Life Database), were analyzed using the maximum likelihood (ML) method. ML analysis of the ITS sequences discriminated isolates from distant geographic origins and particular wild hosts, depending on the fungal species analyzed. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health.

PubMed

Cabello, Felipe C; Godfrey, Henry P; Tomova, Alexandra; Ivanova, Larisa; Dölz, Humberto; Millanao, Ana; Buschmann, Alejandro H

2013-07-01

The worldwide growth of aquaculture has been accompanied by a rapid increase in therapeutic and prophylactic usage of antimicrobials including those important in human therapeutics. Approximately 80% of antimicrobials used in aquaculture enter the environment with their activity intact where they select for bacteria whose resistance arises from mutations or more importantly, from mobile genetic elements containing multiple resistance determinants transmissible to other bacteria. Such selection alters biodiversity in aquatic environments and the normal flora of fish and shellfish. The commonality of the mobilome (the total of all mobile genetic elements in a genome) between aquatic and terrestrial bacteria together with the presence of residual antimicrobials, biofilms, and high concentrations of bacteriophages where the aquatic environment may also be contaminated with pathogens of human and animal origin can stimulate exchange of genetic information between aquatic and terrestrial bacteria. Several recently found genetic elements and resistance determinants for quinolones, tetracyclines, and β-lactamases are shared between aquatic bacteria, fish pathogens, and human pathogens, and appear to have originated in aquatic bacteria. Excessive use of antimicrobials in aquaculture can thus potentially negatively impact animal and human health as well as the aquatic environment and should be better assessed and regulated. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Host–pathogen evolutionary signatures reveal dynamics and future invasions of vampire bat rabies

PubMed Central

Streicker, Daniel G.; Winternitz, Jamie C.; Satterfield, Dara A.; Condori-Condori, Rene Edgar; Broos, Alice; Tello, Carlos; Recuenco, Sergio; Velasco-Villa, Andrés; Altizer, Sonia; Valderrama, William

2016-01-01

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions. PMID:27621441

Common themes in microbial pathogenicity revisited.

PubMed Central

Finlay, B B; Falkow, S

1997-01-01

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics. PMID:9184008

Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

PubMed

Amendola, Laura M; Dorschner, Michael O; Robertson, Peggy D; Salama, Joseph S; Hart, Ragan; Shirts, Brian H; Murray, Mitzi L; Tokita, Mari J; Gallego, Carlos J; Kim, Daniel Seung; Bennett, James T; Crosslin, David R; Ranchalis, Jane; Jones, Kelly L; Rosenthal, Elisabeth A; Jarvik, Ella R; Itsara, Andy; Turner, Emily H; Herman, Daniel S; Schleit, Jennifer; Burt, Amber; Jamal, Seema M; Abrudan, Jenica L; Johnson, Andrew D; Conlin, Laura K; Dulik, Matthew C; Santani, Avni; Metterville, Danielle R; Kelly, Melissa; Foreman, Ann Katherine M; Lee, Kristy; Taylor, Kent D; Guo, Xiuqing; Crooks, Kristy; Kiedrowski, Lesli A; Raffel, Leslie J; Gordon, Ora; Machini, Kalotina; Desnick, Robert J; Biesecker, Leslie G; Lubitz, Steven A; Mulchandani, Surabhi; Cooper, Greg M; Joffe, Steven; Richards, C Sue; Yang, Yaoping; Rotter, Jerome I; Rich, Stephen S; O'Donnell, Christopher J; Berg, Jonathan S; Spinner, Nancy B; Evans, James P; Fullerton, Stephanie M; Leppig, Kathleen A; Bennett, Robin L; Bird, Thomas; Sybert, Virginia P; Grady, William M; Tabor, Holly K; Kim, Jerry H; Bamshad, Michael J; Wilfond, Benjamin; Motulsky, Arno G; Scott, C Ronald; Pritchard, Colin C; Walsh, Tom D; Burke, Wylie; Raskind, Wendy H; Byers, Peter; Hisama, Fuki M; Rehm, Heidi; Nickerson, Debbie A; Jarvik, Gail P

2015-03-01

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. © 2015 Amendola et al.; Published by Cold Spring Harbor Laboratory Press.

Tackling the achilles' heel of genetic testing.

PubMed

Watkins, Hugh

2015-01-14

Assigning pathogenicity to rare genetic variants is at its hardest with the enormous titin gene, but comprehensive genomic analysis makes the task more tractable (Roberts et al., this issue). Copyright © 2015, American Association for the Advancement of Science.

Comparative genomic analysis shows that avian pathogenic Escherichia coli isolate IMT5155 (O2:K1:H5; ST complex 95, ST140) shares close relationship with ST95 APEC O1:K1 and human ExPEC O18:K1 strains.

PubMed

Zhu Ge, Xiangkai; Jiang, Jingwei; Pan, Zihao; Hu, Lin; Wang, Shaohui; Wang, Haojin; Leung, Frederick C; Dai, Jianjun; Fan, Hongjie

2014-01-01

Avian pathogenic E. coli and human extraintestinal pathogenic E. coli serotypes O1, O2 and O18 strains isolated from different hosts are generally located in phylogroup B2 and ST complex 95, and they share similar genetic characteristics and pathogenicity, with no or minimal host specificity. They are popular objects for the study of ExPEC genetic characteristics and pathogenesis in recent years. Here, we investigated the evolution and genetic blueprint of APEC pathotype by performing phylogenetic and comparative genome analysis of avian pathogenic E. coli strain IMT5155 (O2:K1:H5; ST complex 95, ST140) with other E. coli pathotypes. Phylogeny analyses indicated that IMT5155 has closest evolutionary relationship with APEC O1, IHE3034, and UTI89. Comparative genomic analysis showed that IMT5155 and APEC O1 shared significant genetic overlap/similarities with human ExPEC dominant O18:K1 strains (IHE3034 and UTI89). Furthermore, the unique PAI I5155 (GI-12) was identified and found to be conserved in APEC O2 serotype isolates. GI-7 and GI-16 encoding two typical T6SSs in IMT5155 might be useful markers for the identification of ExPEC dominant serotypes (O1, O2, and O18) strains. IMT5155 contained a ColV plasmid p1ColV5155, which defined the APEC pathotype. The distribution analysis of 10 sequenced ExPEC pan-genome virulence factors among 47 sequenced E. coli strains provided meaningful information for B2 APEC/ExPEC-specific virulence factors, including several adhesins, invasins, toxins, iron acquisition systems, and so on. The pathogenicity tests of IMT5155 and other APEC O1:K1 and O2:K1 serotypes strains (isolated in China) through four animal models showed that they were highly virulent for avian colisepticemia and able to cause septicemia and meningitis in neonatal rats, suggesting zoonotic potential of these APEC O1:K1 and O2:K1 isolates.

Genome Sequencing and Mapping Reveal Loss of Heterozygosity as a Mechanism for Rapid Adaptation in the Vegetable Pathogen Phytophthora capsici

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

Lamour, Kurt H.; Mudge, Joann; Gobena, Daniel

2012-02-07

The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diversemore » isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30percent of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici.« less

Ensuring privacy in the study of pathogen genetics

PubMed Central

Mehta, Sanjay R.; Vinterbo, Staal A.; Little, Susan J.

2014-01-01

Rapid growth in the genetic sequencing of pathogens in recent years has led to the creation of large sequence databases. This aggregated sequence data can be very useful for tracking and predicting epidemics of infectious diseases. However, the balance between the potential public health benefit and the risk to personal privacy for individuals whose genetic data (personal or pathogen) are included in such work has been difficult to delineate, because neither the true benefit nor the actual risk to participants has been adequately defined. Existing approaches to minimise the risk of privacy loss to participants are based on de-identification of data by removal of a predefined set of identifiers. These approaches neither guarantee privacy nor protect the usefulness of the data. We propose a new approach to privacy protection that will quantify the risk to participants, while still maximising the usefulness of the data to researchers. This emerging standard in privacy protection and disclosure control, which is known as differential privacy, uses a process-driven rather than data-centred approach to protecting privacy. PMID:24721230

Ensuring privacy in the study of pathogen genetics.

PubMed

Mehta, Sanjay R; Vinterbo, Staal A; Little, Susan J

2014-08-01

Rapid growth in the genetic sequencing of pathogens in recent years has led to the creation of large sequence databases. This aggregated sequence data can be very useful for tracking and predicting epidemics of infectious diseases. However, the balance between the potential public health benefit and the risk to personal privacy for individuals whose genetic data (personal or pathogen) are included in such work has been difficult to delineate, because neither the true benefit nor the actual risk to participants has been adequately defined. Existing approaches to minimise the risk of privacy loss to participants are based on de-identification of data by removal of a predefined set of identifiers. These approaches neither guarantee privacy nor protect the usefulness of the data. We propose a new approach to privacy protection that will quantify the risk to participants, while still maximising the usefulness of the data to researchers. This emerging standard in privacy protection and disclosure control, which is known as differential privacy, uses a process-driven rather than data-centred approach to protecting privacy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Back-trajectories show export of airborne fungal spores (Ganoderma sp.) from forests to agricultural and urban areas in England

NASA Astrophysics Data System (ADS)

Sadyś, M.; Skjøth, C. A.; Kennedy, R.

2014-02-01

We propose here the hypothesis that all of United Kingdom (UK) is likely to be affected by Ganoderma sp. spores, an important plant pathogen. We suggest that the main sources of this pathogen, which acts as a bioaerosol, are the widely scattered woodlands in the country, although remote sources must not be neglected. The hypothesis is based on related studies on bioaerosols and supported by new observations from a non-forest site and model calculations to support our hypothesis.

Pathogenicity variation in two west coast forest Phytophthoras, Phytophthora nemorosa and P. pseudosyringae, to bay laurel

Treesearch

R.E. Linzer; M. Garbelotto

2008-01-01

Two recently described pathogenic oomycetes, Phytophthora nemorosa and P. pseudosyringae, have overlapping host and geographic ranges in California and Oregon forests with P. ramorum, causal agent of ?sudden oak death? disease. Preliminary genetic evidence indicates P. nemorosa and P....

Proceedings of the sudden oak death fifth science symposium

Treesearch

Susan J. Frankel; John T. Kliejunas; Katharine M. Palmieri; Janice M. Alexander

2013-01-01

The Proceedings of the Sudden Oak Death Fifth Science Symposium provides an update on research to address sudden oak death, caused by the exotic, quarantine pathogen, Phytophthora ramorum. Over 60 submissions present national and international investigations covering pathogen biology, biosecurity, genetics, monitoring, fire ecology, and diagnostics...

Evolution of polyketide synthesis in a Dothideomycete forest pathogen

USDA-ARS?s Scientific Manuscript database

Fungal secondary metabolites have many important biological roles and some, like the toxic polyketide aflatoxin, have been intensively studied at the genetic level. Complete sets of polyketide synthase (PKS) genes can now be identified in fungal pathogens by whole genome sequencing and studied in or...

Evolution and diversity of NLR proteins in sugar beets

USDA-ARS?s Scientific Manuscript database

Plants have developed several layers of immunity in order to defend against unrelenting pathogenic attacks. One of these layers is resistance genes. NLR genes are a type of resistance gene, and are involved in pathogen recognition and activation of a hypersensitive response. Genetic data and inferen...

Emergence of the sudden oak death pathogen Phytophthora ramorum

Treesearch

Niklaus J. Grunwald; Matteo Garbelotto; Erica M. Goss; Kurt Huengens; Simone Prospero

2012-01-01

The recently emerged plant pathogen Phytophthora ramorum is responsible for causing the sudden oak death epidemic. This review documents the emergence of P. ramorum based on evolutionary and population genetic analyses. Currently infection by P. ramorum occurs only in Europe and North America and three...

Characterization of microsatellites in Fusicladium effusum, cause of pecan scab

USDA-ARS?s Scientific Manuscript database

Pecan scab, caused by the plant pathogenic fungus Fusicladium effusum, is the most destructive disease of pecan. Little is known of the population genetic diversity of this pathogen. In this study, microsatellites were mined from the F. effusum genome, and flanking primers were subsequently designed...

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...

Application of molecular genetic tools to studies of forest pathosystems [Chapter 2

Treesearch

Mee-Sook Kim; Ned B. Klopfenstein; Richard C. Hamelin

2005-01-01

The use of molecular genetics in forest pathology has greatly increased over the past 10 years. For the most part, molecular genetic tools were initially developed to focus on individual components (e.g., pathogen, host) of forest pathosystems. As part of broader forest ecosystem complexes, forest pathosystems involve dynamic interactions among living components (e.g...

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

USDA-ARS?s Scientific Manuscript database

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

Banking on the future: progress, challenges and opportunities for the genetic conservation of forest trees

Treesearch

Kevin M. Potter; Robert M. Jetton; Andrew Bower; Douglass F. Jacobs; Gary Man; Valerie D. Hipkins; Murphy Westwood

2017-01-01

Genetic diversity provides the essential basis for the adaptation and resilience of tree species to environmental stress and change. The genetic conservation of tree species is an urgent global necessity as forest conversion and fragmentation continue apace, damaging insects and pathogens are transported between continents, and climate change alters local habitat...

Combining Quantitative Genetic Footprinting and Trait Enrichment Analysis to Identify Fitness Determinants of a Bacterial Pathogen

PubMed Central

Wiles, Travis J.; Norton, J. Paul; Russell, Colin W.; Dalley, Brian K.; Fischer, Kael F.; Mulvey, Matthew A.

2013-01-01

Strains of Extraintestinal Pathogenic Escherichia c oli (ExPEC) exhibit an array of virulence strategies and are a major cause of urinary tract infections, sepsis and meningitis. Efforts to understand ExPEC pathogenesis are challenged by the high degree of genetic and phenotypic variation that exists among isolates. Determining which virulence traits are widespread and which are strain-specific will greatly benefit the design of more effective therapies. Towards this goal, we utilized a quantitative genetic footprinting technique known as transposon insertion sequencing (Tn-seq) in conjunction with comparative pathogenomics to functionally dissect the genetic repertoire of a reference ExPEC isolate. Using Tn-seq and high-throughput zebrafish infection models, we tracked changes in the abundance of ExPEC variants within saturated transposon mutant libraries following selection within distinct host niches. Nine hundred and seventy bacterial genes (18% of the genome) were found to promote pathogen fitness in either a niche-dependent or independent manner. To identify genes with the highest therapeutic and diagnostic potential, a novel Trait Enrichment Analysis (TEA) algorithm was developed to ascertain the phylogenetic distribution of candidate genes. TEA revealed that a significant portion of the 970 genes identified by Tn-seq have homologues more often contained within the genomes of ExPEC and other known pathogens, which, as suggested by the first axiom of molecular Koch's postulates, is considered to be a key feature of true virulence determinants. Three of these Tn-seq-derived pathogen-associated genes—a transcriptional repressor, a putative metalloendopeptidase toxin and a hypothetical DNA binding protein—were deleted and shown to independently affect ExPEC fitness in zebrafish and mouse models of infection. Together, the approaches and observations reported herein provide a resource for future pathogenomics-based research and highlight the diversity of factors required by a single ExPEC isolate to survive within varying host environments. PMID:23990803

Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder.

PubMed

Wang, Yiqin; Picard, Martin; Gu, Zhenglong

2016-10-01

Increasing clinical and biochemical evidence implicate mitochondrial dysfunction in the pathophysiology of Autism Spectrum Disorder (ASD), but little is known about the biological basis for this connection. A possible cause of ASD is the genetic variation in the mitochondrial DNA (mtDNA) sequence, which has yet to be thoroughly investigated in large genomic studies of ASD. Here we evaluated mtDNA variation, including the mixture of different mtDNA molecules in the same individual (i.e., heteroplasmy), using whole-exome sequencing data from mother-proband-sibling trios from simplex families (n = 903) where only one child is affected by ASD. We found that heteroplasmic mutations in autistic probands were enriched at non-polymorphic mtDNA sites (P = 0.0015), which were more likely to confer deleterious effects than heteroplasmies at polymorphic mtDNA sites. Accordingly, we observed a ~1.5-fold enrichment of nonsynonymous mutations (P = 0.0028) as well as a ~2.2-fold enrichment of predicted pathogenic mutations (P = 0.0016) in autistic probands compared to their non-autistic siblings. Both nonsynonymous and predicted pathogenic mutations private to probands conferred increased risk of ASD (Odds Ratio, OR[95% CI] = 1.87[1.14-3.11] and 2.55[1.26-5.51], respectively), and their influence on ASD was most pronounced in families with probands showing diminished IQ and/or impaired social behavior compared to their non-autistic siblings. We also showed that the genetic transmission pattern of mtDNA heteroplasmies with high pathogenic potential differed between mother-autistic proband pairs and mother-sibling pairs, implicating developmental and possibly in utero contributions. Taken together, our genetic findings substantiate pathogenic mtDNA mutations as a potential cause for ASD and synergize with recent work calling attention to their unique metabolic phenotypes for diagnosis and treatment of children with ASD.

Combination of RNAseq and SNP nanofluidic array reveals the center of genetic diversity of cacao pathogen Moniliophthora roreri in the upper Magdalena Valley of Colombia and its clonality.

PubMed

Ali, Shahin S; Shao, Jonathan; Strem, Mary D; Phillips-Mora, Wilberth; Zhang, Dapeng; Meinhardt, Lyndel W; Bailey, Bryan A

2015-01-01

Moniliophthora roreri is the fungal pathogen that causes frosty pod rot (FPR) disease of Theobroma cacao L., the source of chocolate. FPR occurs in most of the cacao producing countries in the Western Hemisphere, causing yield losses up to 80%. Genetic diversity within the FPR pathogen population may allow the population to adapt to changing environmental conditions and adapt to enhanced resistance in the host plant. The present study developed single nucleotide polymorphism (SNP) markers from RNASeq results for 13 M. roreri isolates and validated the markers for their ability to reveal genetic diversity in an international M. roreri collection. The SNP resources reported herein represent the first study of RNA sequencing (RNASeq)-derived SNP validation in M. roreri and demonstrates the utility of RNASeq as an approach for de novo SNP identification in M. roreri. A total of 88 polymorphic SNPs were used to evaluate the genetic diversity of 172 M. roreri cacao isolates resulting in 37 distinct genotypes (including 14 synonymous groups). Absence of heterozygosity for the 88 SNP markers indicates reproduction in M. roreri is clonal and likely due to a homothallic life style. The upper Magdalena Valley of Colombia showed the highest levels of genetic diversity with 20 distinct genotypes of which 13 were limited to this region, and indicates this region as the possible center of origin for M. roreri.

Combination of RNAseq and SNP nanofluidic array reveals the center of genetic diversity of cacao pathogen Moniliophthora roreri in the upper Magdalena Valley of Colombia and its clonality

PubMed Central

Ali, Shahin S.; Shao, Jonathan; Strem, Mary D.; Phillips-Mora, Wilberth; Zhang, Dapeng; Meinhardt, Lyndel W.; Bailey, Bryan A.

2015-01-01

Moniliophthora roreri is the fungal pathogen that causes frosty pod rot (FPR) disease of Theobroma cacao L., the source of chocolate. FPR occurs in most of the cacao producing countries in the Western Hemisphere, causing yield losses up to 80%. Genetic diversity within the FPR pathogen population may allow the population to adapt to changing environmental conditions and adapt to enhanced resistance in the host plant. The present study developed single nucleotide polymorphism (SNP) markers from RNASeq results for 13 M. roreri isolates and validated the markers for their ability to reveal genetic diversity in an international M. roreri collection. The SNP resources reported herein represent the first study of RNA sequencing (RNASeq)-derived SNP validation in M. roreri and demonstrates the utility of RNASeq as an approach for de novo SNP identification in M. roreri. A total of 88 polymorphic SNPs were used to evaluate the genetic diversity of 172 M. roreri cacao isolates resulting in 37 distinct genotypes (including 14 synonymous groups). Absence of heterozygosity for the 88 SNP markers indicates reproduction in M. roreri is clonal and likely due to a homothallic life style. The upper Magdalena Valley of Colombia showed the highest levels of genetic diversity with 20 distinct genotypes of which 13 were limited to this region, and indicates this region as the possible center of origin for M. roreri. PMID:26379633

Genome dynamics and its impact on evolution of Escherichia coli.

PubMed

Dobrindt, Ulrich; Chowdary, M Geddam; Krumbholz, G; Hacker, J

2010-08-01

The Escherichia coli genome consists of a conserved part, the so-called core genome, which encodes essential cellular functions and of a flexible, strain-specific part. Genes that belong to the flexible genome code for factors involved in bacterial fitness and adaptation to different environments. Adaptation includes increase in fitness and colonization capacity. Pathogenic as well as non-pathogenic bacteria carry mobile and accessory genetic elements such as plasmids, bacteriophages, genomic islands and others, which code for functions required for proper adaptation. Escherichia coli is a very good example to study the interdependency of genome architecture and lifestyle of bacteria. Thus, these species include pathogenic variants as well as commensal bacteria adapted to different host organisms. In Escherichia coli, various genetic elements encode for pathogenicity factors as well as factors, which increase the fitness of non-pathogenic bacteria. The processes of genome dynamics, such as gene transfer, genome reduction, rearrangements as well as point mutations contribute to the adaptation of the bacteria into particular environments. Using Escherichia coli model organisms, such as uropathogenic strain 536 or commensal strain Nissle 1917, we studied mechanisms of genome dynamics and discuss these processes in the light of the evolution of microbes.

Highly sensitive and quantitative detection of rare pathogens through agarose droplet microfluidic emulsion PCR at the single-cell level.

PubMed

Zhu, Zhi; Zhang, Wenhua; Leng, Xuefei; Zhang, Mingxia; Guan, Zhichao; Lu, Jiangquan; Yang, Chaoyong James

2012-10-21

Genetic alternations can serve as highly specific biomarkers to distinguish fatal bacteria or cancer cells from their normal counterparts. However, these mutations normally exist in very rare amount in the presence of a large excess of non-mutated analogs. Taking the notorious pathogen E. coli O157:H7 as the target analyte, we have developed an agarose droplet-based microfluidic ePCR method for highly sensitive, specific and quantitative detection of rare pathogens in the high background of normal bacteria. Massively parallel singleplex and multiplex PCR at the single-cell level in agarose droplets have been successfully established. Moreover, we challenged the system with rare pathogen detection and realized the sensitive and quantitative analysis of a single E. coli O157:H7 cell in the high background of 100,000 excess normal K12 cells. For the first time, we demonstrated rare pathogen detection through agarose droplet microfluidic ePCR. Such a multiplex single-cell agarose droplet amplification method enables ultra-high throughput and multi-parameter genetic analysis of large population of cells at the single-cell level to uncover the stochastic variations in biological systems.

[The detection of strains of Esherichia coll producing Shiga toxin in populations of normal intestinal microbiota in children with functional disorders of gastrointestinal tract].

PubMed

Ivanova, E I; Popkova, S M; Dzhioev, Iu P; Rakova, E B; Nemchenko, U M; Rychkova, L V

2014-11-01

In intestinal ecosystem, interchange of genetic material between different types of bacteria and other representatives of family Enterobacteriaceae results in development of types of normal colibacillus with genetic characteristics of pathogenicity. This occurrence can be considered as a theoretical substantiation for labeling such strains as pathobionts. The polymerase chain reaction was implemented to analyze 96 strains of different types of Escherichia coli (with normal and weak zymogenic activity and hemolytic activity) isolated from children with functional disorders of gastrointestinal tract. The purpose was to detect presence of gens coding capacity of toxin production (six1, stx2). In intestinal biotope of children, circulation of strains of Escherichia coli producing shiga toxin having no relation to pathogenic group being representatives of normal indigenous microbiota. The presence of gens stx1 and stx2 in various biochemical types of Escherichia coli permits establishing fact of forming of reservoir of potential pathogenicity in non-pathogenic forms of Escherichia coli. The presence of gen (verotoxin 1) in genome of various types of Escherichia coli isolated from one single biotope testifies possible horizontal transmission of factors of pathogenicity in intestinal biotope.

The wild tomato species Solanum chilense shows variation in pathogen resistance between geographically distinct populations

PubMed Central

Scheikl, Daniela; Tellier, Aurélien

2017-01-01

Wild tomatoes are a valuable source of disease resistance germplasm for tomato (Solanum lycopersicum) breeders. Many species are known to possess a certain degree of resistance against certain pathogens; however, evolution of resistance traits is yet poorly understood. For some species, like Solanum chilense, both differences in habitat and within species genetic diversity are very large. Here we aim to investigate the occurrence of spatially heterogeneous coevolutionary pressures between populations of S. chilense. We investigate the phenotypic differences in disease resistance within S. chilense against three common tomato pathogens (Alternaria solani, Phytophthora infestans and a Fusarium sp.) and confirm high degrees of variability in resistance properties between selected populations. Using generalised linear mixed models, we show that disease resistance does not follow the known demographic patterns of the species. Models with up to five available climatic and geographic variables are required to best describe resistance differences, confirming the complexity of factors involved in local resistance variation. We confirm that within S. chilense, resistance properties against various pathogens show a mosaic pattern and do not follow environmental patterns, indicating the strength of local pathogen pressures. Our study can form the basis for further investigations of the genetic traits involved. PMID:28133579

The wild tomato species Solanum chilense shows variation in pathogen resistance between geographically distinct populations.

PubMed

Stam, Remco; Scheikl, Daniela; Tellier, Aurélien

2017-01-01

Wild tomatoes are a valuable source of disease resistance germplasm for tomato ( Solanum lycopersicum ) breeders. Many species are known to possess a certain degree of resistance against certain pathogens; however, evolution of resistance traits is yet poorly understood. For some species, like Solanum chilense , both differences in habitat and within species genetic diversity are very large. Here we aim to investigate the occurrence of spatially heterogeneous coevolutionary pressures between populations of S. chilense . We investigate the phenotypic differences in disease resistance within S. chilense against three common tomato pathogens ( Alternaria solani , Phytophthora infestans and a Fusarium sp .) and confirm high degrees of variability in resistance properties between selected populations. Using generalised linear mixed models, we show that disease resistance does not follow the known demographic patterns of the species. Models with up to five available climatic and geographic variables are required to best describe resistance differences, confirming the complexity of factors involved in local resistance variation. We confirm that within S. chilense , resistance properties against various pathogens show a mosaic pattern and do not follow environmental patterns, indicating the strength of local pathogen pressures. Our study can form the basis for further investigations of the genetic traits involved.

Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl

USGS Publications Warehouse

Gaidet, N.; Cattoli, G.; Hammoumi, S.; Newman, S.H.; Hagemeijer, W.; Takekawa, John Y.; Cappelle, J.; Dodman, T.; Joannis, T.; Gil, P.; Monne, I.; Fusaro, A.; Capua, I.; Manu, S.; Micheloni, P.; Ottosson, U.; Mshelbwala, J.H.; Lubroth, J.; Domenech, J.; Monicat, F.

2008-01-01

The potential existence of a wild bird reservoir for highly pathogenic avian influenza (HPAI) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses, responsible for concurrent outbreaks in migratory and domestic birds over Asia, Europe, and Africa. During a large-scale surveillance programme over Eastern Europe, the Middle East, and Africa, we detected avian influenza viruses of H5N2 subtype with a highly pathogenic (HP) viral genotype in healthy birds of two wild waterfowl species sampled in Nigeria. We monitored the survival and regional movements of one of the infected birds through satellite telemetry, providing a rare evidence of a non-lethal natural infection by an HP viral genotype in wild birds. Phylogenetic analysis of the H5N2 viruses revealed close genetic relationships with H5 viruses of low pathogenicity circulating in Eurasian wild and domestic ducks. In addition, genetic analysis did not reveal known gallinaceous poultry adaptive mutations, suggesting that the emergence of HP strains could have taken place in either wild or domestic ducks or in non-gallinaceous species. The presence of coexisting but genetically distinguishable avian influenza viruses with an HP viral genotype in two cohabiting species of wild waterfowl, with evidence of non-lethal infection at least in one species and without evidence of prior extensive circulation of the virus in domestic poultry, suggest that some strains with a potential high pathogenicity for poultry could be maintained in a community of wild waterfowl.

Genetic testing of the FBN1 gene in Chinese patients with Marfan/Marfan-like syndrome.

PubMed

Yang, Hang; Luo, Mingyao; Chen, Qianlong; Fu, Yuanyuan; Zhang, Jing; Qian, Xiangyang; Sun, Xiaogang; Fan, Yuxin; Zhou, Zhou; Chang, Qian

2016-08-01

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder typically involving the ocular, skeletal and cardiovascular systems, and aortic aneurysms/dissection mainly contributes to its mortality. Here, we performed genetic testing of the FBN1 gene in 39 Chinese probands with Marfan/Marfan-like syndrome and their related family members by Sanger sequencing. In total, 29 pathogenic/likely pathogenic FBN1 mutations, including 17 novel ones, were identified. In addition, most MFS patients with aortic disease (62%) had a truncating or splicing mutation. These results expand the FBN1 mutation spectrum and enrich our knowledge of genotype-phenotype correlations. Genetic testing for MFS and its related aortic diseases is increasingly important for early intervention and treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetics-based methods for detection of Salmonella spp. in foods.

PubMed

Mozola, Mark A

2006-01-01

Genetic methods are now at the forefront of foodborne pathogen testing. The sensitivity, specificity, and inclusivity advantages offered by deoxyribonucleic acid (DNA) probe technology have driven an intense effort in methods development over the past 20 years. DNA probe-based methods for Salmonella spp. and other pathogens have progressed from time-consuming procedures involving the use of radioisotopes to simple, high throughput, automated assays. The analytical sensitivity of nucleic acid amplification technology has facilitated a reduction in analysis time by allowing enriched samples to be tested for previously undetectable quantities of analyte. This article will trace the evolution of the development of genetic methods for detection of Salmonella in foods, review the basic assay formats and their advantages and limitations, and discuss method performance characteristics and considerations for selection of methods.

Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

USDA-ARS?s Scientific Manuscript database

Novel subtypes of Eurasian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4 such as H5N2, H5N5, H5N6, and H5N8 have been identified in China since 2008 and subsequently evolved into four genetically distinct groups (A – D) of clade 2.3.4.4...

Horizontal gene acquisitions, mobile element proliferation, and genome decay in the host-restricted plant pathogen erwinia tracheiphila

USDA-ARS?s Scientific Manuscript database

Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains o...

Phylogenetics of a fungal invasion: origins and widespread dispersal of white-nose syndrome

Treesearch

Kevin P. Drees; Jeffrey M. Lorch; Sebastien J. Puechmaille; Katy L. Parise; Gudrun Wibbelt; Joseph R. Hoyt; Keping Sun; Ariunbold Jargalsaikhan; Munkhnast Dalannast; Jonathan M. Palmer; Daniel L. Lindner; A. Marm Kilpatrick; Talima Pearson; Paul S. Keim; David S. Blehert; Jeffrey T. Foster; Joseph Heitman

2017-01-01

Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates. Pseudogymnoascus destructans, a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has...

Draft genome sequences of 50 MRSA ST5 isolates obtained from a U.S. hospital

USDA-ARS?s Scientific Manuscript database

Methicillin resistant Staphylococcus aureus (MRSA) can be a commensal or pathogen in humans. Pathogenicity and disease are related to the acquisition of mobile genetic elements encoding virulence and antimicrobial resistance genes. Here, we report draft genome sequences for 50 clinical MRSA isolates...

Studying plant-pathogen interactions in the genomics era: beyond molecular Koch’s postulates to systems biology

USDA-ARS?s Scientific Manuscript database

Molecular factors enabling microbial pathogens to cause plant diseases have been sought with increasing efficacy over three research eras, which successively introduced the tools of disease physiology, single-gene molecular genetics, and genomics. From this work emerged a unified model of the intera...

Assessing forest-pathogen interactions at the population level [Chapter 3

Treesearch

Bryce Richardson; Ned B. Klopfenstein; Tobin L. Peever

2005-01-01

During most of the past century, forest pathologists were limited to the study of pathogen phenotypes, vegetative compatibility, and mating reactions. These studies provided important insights in fungal taxonomy and phylogenetics, reproductive biology, and population genetics. However, these aspects are insufficiently variable or technically unfeasible for making...

Geographic isolates of Lymantria dispar multiple nucleopolyhedrovirus: Genome sequence analysis and pathogenicity against European and Asian gypsy moth strains

USDA-ARS?s Scientific Manuscript database

Geographic isolates of Lymantria dispar multiple nucleopolyhedrovirus: Genome sequence analysis and pathogenicity against European and Asian gypsy moth strains. To evaluate the genetic diversity of Lymantria dispar nucleopolyhedrovirus (LdMNPV) at the genomic level, the genomes of three isolates of...

Analysis of genome sequences from plant pathogenic Rhodococcus reveals genetic novelties in virulence loci

USDA-ARS?s Scientific Manuscript database

Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model predicts that phytopathogenic isolates require a cluster of thre...

Important Hawaiian tree species in need of genetic conservation

Treesearch

Robert D. Hauff

2017-01-01

Resource managers in Hawaii face unique forest conservation challenges. Invasive species continue to inundate the remote island archipelago, directly threatening its forest resources. Hawaii has the largest number (> 400) of endangered plants in the United States, and managers use genetic approaches to preserve these small populations which are often island...

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses

PubMed Central

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nuntawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-01-01

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate (A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby Canine Kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 29 HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. PMID:22230579

Genetic analysis of Enterobius vermicularis isolated from a chimpanzee with lethal hemorrhagic colitis and pathology of the associated lesions.

PubMed

Yaguchi, Yuji; Okabayashi, Sachi; Abe, Niichiro; Masatou, Haruhisa; Iida, Shinya; Teramoto, Isao; Matsubayashi, Makoto; Shibahara, Tomoyuki

2014-11-01

Human pinworms, Enterobius vermicularis, are normally recognized as minor pathogens. However, a fatal case of human pinworm infection has been reported in a nonhuman primate, a zoo reared chimpanzee. Here, we histopathologically examined the lesions in tissues from the deceased chimpanzee and genetically characterized the isolated worms to investigate the pathogenicity and determine the phylogeny. We identified ulcers deep in the submucosa where many parasites were found to have invaded the lamina propria mucosa or submucous tissue. An inflammatory reaction consisting mainly of neutrophils and lymphocytes but not eosinophils was observed around the parasites, and intense hemorrhage in the lamina propria was confirmed. The parasites were morphologically similar to E. vermicularis based on the shape of the copulatory spicules. Mitochondrial cytochrome c oxidase subunit 1 gene products were amplified from worm DNA by PCR and were genetically identified as E. vermicularis based on >98.7% similarity of partial sequences. Phylogenetic analysis revealed that the sequences clustered together with other chimpanzee E. vermicularis isolates in a group which has been referred to as type C and which differs from human isolates (type A). The samples were negative for bacterial pathogens and Entamoeba histolytica indicating that E. vermicularis could be pathogenic in chimpanzees. Phylogenetic clustering of the isolates indicated that the parasite may be host specific.

Fecundity compensation and tolerance to a sterilizing pathogen in Daphnia.

PubMed

Vale, P F; Little, T J

2012-09-01

Hosts are armed with several lines of defence in the battle against parasites: they may prevent the establishment of infection, reduce parasite growth once infected or persevere through mechanisms that reduce the damage caused by infection, called tolerance. Studies on tolerance in animals have focused on mortality, and sterility tolerance has not been investigated experimentally. Here, we tested for genetic variation in the multiple steps of defence when the invertebrate Daphnia magna is infected with the sterilizing bacterial pathogen Pasteuria ramosa: anti-infection resistance, anti-growth resistance and the ability to tolerate sterilization once infected. When exposed to nine doses of a genetically diverse pathogen inoculum, six host genotypes varied in their average susceptibility to infection and in their parasite loads once infected. How host fecundity changed with increasing parasite loads did not vary between genotypes, indicating that there was no genetic variation for this measure of fecundity tolerance. However, genotypes differed in their level of fecundity compensation under infection, and we discuss how, by increasing host fitness without targeting parasite densities, fecundity compensation is consistent with the functional definition of tolerance. Such infection-induced life-history shifts are not traditionally considered to be part of the immune response, but may crucially reduce harm (in terms of fitness loss) caused by disease, and are a distinct source of selection on pathogens. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Malagasy bats shelter a considerable genetic diversity of pathogenic Leptospira suggesting notable host-specificity patterns.

PubMed

Gomard, Yann; Dietrich, Muriel; Wieseke, Nicolas; Ramasindrazana, Beza; Lagadec, Erwan; Goodman, Steven M; Dellagi, Koussay; Tortosa, Pablo

2016-04-01

Pathogenic Leptospira are the causative agents of leptospirosis, a disease of global concern with major impact in tropical regions. Despite the importance of this zoonosis for human health, the evolutionary and ecological drivers shaping bacterial communities in host reservoirs remain poorly investigated. Here, we describe Leptospira communities hosted by Malagasy bats, composed of mostly endemic species, in order to characterize host-pathogen associations and investigate their evolutionary histories. We screened 947 individual bats (representing 31 species, 18 genera and seven families) for Leptospira infection and subsequently genotyped positive samples using three different bacterial loci. Molecular identification showed that these Leptospira are notably diverse and include several distinct lineages mostly belonging to Leptospira borgpetersenii and L. kirschneri. The exploration of the most probable host-pathogen evolutionary scenarios suggests that bacterial genetic diversity results from a combination of events related to the ecology and the evolutionary history of their hosts. Importantly, based on the data set presented herein, the notable host-specificity we have uncovered, together with a lack of geographical structuration of bacterial genetic diversity, indicates that the Leptospira community at a given site depends on the co-occurring bat species assemblage. The implications of such tight host-specificity on the epidemiology of leptospirosis are discussed. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular ecology meets remote sensing: environmental drivers to population structure of humpback dolphins in the Western Indian Ocean.

PubMed

Mendez, M; Subramaniam, A; Collins, T; Minton, G; Baldwin, R; Berggren, P; Särnblad, A; Amir, O A; Peddemors, V M; Karczmarski, L; Guissamulo, A; Rosenbaum, H C

2011-10-01

Genetic analyses of population structure can be placed in explicit environmental contexts if appropriate environmental data are available. Here, we use high-coverage and high-resolution oceanographic and genetic sequence data to assess population structure patterns and their potential environmental influences for humpback dolphins in the Western Indian Ocean. We analyzed mitochondrial DNA data from 94 dolphins from the coasts of South Africa, Mozambique, Tanzania and Oman, employing frequency-based and maximum-likelihood algorithms to assess population structure and migration patterns. The genetic data were combined with 13 years of remote sensing oceanographic data of variables known to influence cetacean dispersal and population structure. Our analyses show strong and highly significant genetic structure between all putative populations, except for those in South Africa and Mozambique. Interestingly, the oceanographic data display marked environmental heterogeneity between all sampling areas and a degree of overlap between South Africa and Mozambique. Our combined analyses therefore suggest the occurrence of genetically isolated populations of humpback dolphins in areas that are environmentally distinct. This study highlights the utility of molecular tools in combination with high-resolution and high-coverage environmental data to address questions not only pertaining to genetic population structure, but also to relevant ecological processes in marine species.

Genetic Evidence for Modifying Oceanic Boundaries Relative to Fiji.

PubMed

Shipley, Gerhard P; Taylor, Diana A; N'Yeurt, Antoine D R; Tyagi, Anand; Tiwari, Geetanjali; Redd, Alan J

2016-07-01

We present the most comprehensive genetic characterization to date of five Fijian island populations: Viti Levu, Vanua Levu, Kadavu, the Lau Islands, and Rotuma, including nonrecombinant Y (NRY) chromosome and mitochondrial DNA (mtDNA) haplotypes and haplogroups. As a whole, Fijians are genetically intermediate between Melanesians and Polynesians, but the individual Fijian island populations exhibit significant genetic structure reflecting different settlement experiences in which the Rotumans and the Lau Islanders were more influenced by Polynesians, and the other Fijian island populations were more influenced by Melanesians. In particular, Rotuman and Lau Islander NRY chromosomal and mtDNA haplogroup frequencies and Rotuman mtDNA hypervariable segment 1 region haplotypes more closely resemble those of Polynesians, while genetic markers of the other populations more closely resemble those of the Near Oceanic Melanesians. Our findings provide genetic evidence supportive of modifying regional boundaries relative to Fiji, as has been suggested by others based on a variety of nongenetic evidence. Specifically, for the traditional Melanesia/Polynesia/Micronesia scheme, our findings support moving the Melanesia-Polynesia boundary to include Rotuma and the Lau Islands in Polynesia. For the newer Near/Remote Oceania scheme, our findings support keeping Rotuma and the Lau Islands in Remote Oceania and locating the other Fijian island populations in an intermediate or "Central Oceania" region to better reflect the great diversity of Oceania.

Molecular ecology meets remote sensing: environmental drivers to population structure of humpback dolphins in the Western Indian Ocean

PubMed Central

Mendez, M; Subramaniam, A; Collins, T; Minton, G; Baldwin, R; Berggren, P; Särnblad, A; Amir, O A; Peddemors, V M; Karczmarski, L; Guissamulo, A; Rosenbaum, H C

2011-01-01

Genetic analyses of population structure can be placed in explicit environmental contexts if appropriate environmental data are available. Here, we use high-coverage and high-resolution oceanographic and genetic sequence data to assess population structure patterns and their potential environmental influences for humpback dolphins in the Western Indian Ocean. We analyzed mitochondrial DNA data from 94 dolphins from the coasts of South Africa, Mozambique, Tanzania and Oman, employing frequency-based and maximum-likelihood algorithms to assess population structure and migration patterns. The genetic data were combined with 13 years of remote sensing oceanographic data of variables known to influence cetacean dispersal and population structure. Our analyses show strong and highly significant genetic structure between all putative populations, except for those in South Africa and Mozambique. Interestingly, the oceanographic data display marked environmental heterogeneity between all sampling areas and a degree of overlap between South Africa and Mozambique. Our combined analyses therefore suggest the occurrence of genetically isolated populations of humpback dolphins in areas that are environmentally distinct. This study highlights the utility of molecular tools in combination with high-resolution and high-coverage environmental data to address questions not only pertaining to genetic population structure, but also to relevant ecological processes in marine species. PMID:21427750

Genetic structure of the fungal grapevine pathogen Eutypa lata from four continents

USDA-ARS?s Scientific Manuscript database

The generalist ascomycete fungus Eutypa lata causes Eutypa dieback of grapevine (Vitis vinifera) worldwide. To decipher the cosmopolitan distribution of this fungus, the population genetic structure of 17 geographic samples was investigated from four continental regions (Australia, California, Europ...

Cat-rodent Toxoplasma gondii Type II-variant circulation and limited genetic diversity on the Island of Fernando de Noronha, Brazil

USDA-ARS?s Scientific Manuscript database

In Brazil, studies on animals and humans in mainland areas have shown that most strains of Toxoplasma gondii are pathogenic to mice and exhibit great genetic variability. In this study, using a set of 11 PCR-RFLP and 15 microsatellite markers, we isolated and genetically characterised T. gondii stra...

Identification of Pseudomonas syringae pathogens of Arabidopsis and a bacterial locus determining avirulence on both Arabidopsis and soybean.

PubMed

Whalen, M C; Innes, R W; Bent, A F; Staskawicz, B J

1991-01-01

To develop a model system for molecular genetic analysis of plant-pathogen interactions, we studied the interaction between Arabidopsis thaliana and the bacterial pathogen Pseudomonas syringae pv tomato (Pst). Pst strains were found to be virulent or avirulent on specific Arabidopsis ecotypes, and single ecotypes were resistant to some Pst strains and susceptible to others. In many plant-pathogen interactions, disease resistance is controlled by the simultaneous presence of single plant resistance genes and single pathogen avirulence genes. Therefore, we tested whether avirulence genes in Pst controlled induction of resistance in Arabidopsis. Cosmids that determine avirulence were isolated from Pst genomic libraries, and the Pst avirulence locus avrRpt2 was defined. This allowed us to construct pathogens that differed only by the presence or absence of a single putative avirulence gene. We found that Arabidopsis ecotype Col-0 was susceptible to Pst strain DC3000 but resistant to the same strain carrying avrRpt2, suggesting that a single locus in Col-0 determines resistance. As a first step toward genetically mapping the postulated resistance locus, an ecotype susceptible to infection by DC3000 carrying avrRpt2 was identified. The avrRpt2 locus from Pst was also moved into virulent strains of the soybean pathogen P. syringae pv glycinea to test whether this locus could determine avirulence on soybean. The resulting strains induced a resistant response in a cultivar-specific manner, suggesting that similar resistance mechanisms may function in Arabidopsis and soybean.

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

PubMed Central

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

2015-01-01

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

Host genetics affect microbial ecosystems via host immunity.

PubMed

El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

2016-10-01

Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

Genetic variation affecting host-parasite interactions: major-effect quantitative trait loci affect the transmission of sigma virus in Drosophila melanogaster.

PubMed

Bangham, Jenny; Knott, Sara A; Kim, Kang-Wook; Young, Robert S; Jiggins, Francis M

2008-09-01

In natural populations, genetic variation affects resistance to disease. Whether that genetic variation comprises lots of small-effect polymorphisms or a small number of large-effect polymorphisms has implications for adaptation, selection and how genetic variation is maintained in populations. Furthermore, how much genetic variation there is, and the genes that underlie this variation, affects models of co-evolution between parasites and their hosts. We are studying the genetic variation that affects the resistance of Drosophila melanogaster to its natural pathogen--the vertically transmitted sigma virus. We have carried out three separate quantitative trait locus mapping analyses to map gene variants on the second chromosome that cause variation in the rate at which males transmit the infection to their offspring. All three crosses identified a locus in a similar chromosomal location that causes a large drop in the rate at which the virus is transmitted. We also found evidence for an additional smaller-effect quantitative trait locus elsewhere on the chromosome. Our data, together with previous experiments on the sigma virus and parasitoid wasps, indicate that the resistance of D. melanogaster to co-evolved pathogens is controlled by a limited number of major-effect polymorphisms.

Estimating the microbiological risks associated with inland flood events: Bridging theory and models of pathogen transport

PubMed Central

Collender, Philip A.; Cooke, Olivia C.; Bryant, Lee D.; Kjeldsen, Thomas R.; Remais, Justin V.

2017-01-01

Flooding is known to facilitate infectious disease transmission, yet quantitative research on microbiological risks associated with floods has been limited. Pathogen fate and transport models provide a framework to examine interactions between landscape characteristics, hydrology, and waterborne disease risks, but have not been widely developed for flood conditions. We critically examine capabilities of current hydrological models to represent unusual flow paths, non-uniform flow depths, and unsteady flow velocities that accompany flooding. We investigate the theoretical linkages between hydrodynamic processes and spatio-temporally variable suspension and deposition of pathogens from soils and sediments; pathogen dispersion in flow; and concentrations of constituents influencing pathogen transport and persistence. Identifying gaps in knowledge and modeling practice, we propose a research agenda to strengthen microbial fate and transport modeling applied to inland floods: 1) development of models incorporating pathogen discharges from flooded sources (e.g., latrines), effects of transported constituents on pathogen persistence, and supply-limited pathogen transport; 2) studies assessing parameter identifiability and comparing model performance under varying degrees of process representation, in a range of settings; 3) development of remotely sensed datasets to support modeling of vulnerable, data-poor regions; and 4) collaboration between modelers and field-based researchers to expand the collection of useful data in situ. PMID:28757789

Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease.

PubMed

Underhill, R A

2015-12-01

The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors. Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen. ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases. Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients' genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks. The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients' immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen. Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins; various infectious diseases preceding the onset of ME/CFS; and occupational exposure of health care professionals. The hypothesis implies that ME/CFS patients should not donate blood or tissue and usual precautions should be taken when handling patients' blood and tissue. No known pathogen has been shown to cause ME/CFS. Confirmation of the hypothesis requires identification of a causal pathogen. Research should focus on a search for unknown and known pathogens. Finding a causal pathogen could assist with diagnosis; help find a biomarker; enable the development of anti-microbial treatments; suggest preventive measures; explain pathophysiological findings; and reassure patients about the validity of their symptoms.

Spontaneous bacterial and fungal infections in genetically engineered mice: Is Escherichia coli an emerging pathogen in laboratory mouse?

PubMed

Benga, Laurentiu; Benten, W Peter M; Engelhardt, Eva; Gougoula, Christina; Sager, Martin

2015-01-01

The impact of particular microbes on genetically engineered mice depends on the genotype and the environment. Infections resulting in clinical disease have an obvious impact on animal welfare and experimentation. In this study, we investigated the bacterial and fungal aetiology of spontaneous clinical disease of infectious origin among the genetically engineered mice from our institution in relation to their genotype. A total of 63 mice belonging to 33 different mice strains, from severe immunodeficient to wild-type, were found to display infections as the primary cause leading to their euthanasia. The necropsies revealed abscesses localized subcutaneously as well as in the kidney, preputial glands, seminal vesicles, in the uterus, umbilicus or in the lung. In addition, pneumonia, endometritis and septicaemia cases were recorded. Escherichia coli was involved in 21 of 44 (47.72%) of the lesions of bacterial origin, whereas [Pasteurella] pneumotropica was isolated from 19 of 44 (43.18%) cases. The infections with the two agents mentioned above included three cases of mixed infection with both pathogens. Staphylococcus aureus was considered responsible for five of 44 (11.36%) cases whereas Enterobacter cloacae was found to cause lesions in two of 44 (4.54%) mice. Overall, 16 of the 44 (36.36%) cases of bacterial aetiology affected genetically engineered mice without any explicit immunodeficiency or wild-type strains. The remaining 19 cases of interstitial pneumonia were caused by Pneumocystis murina. In conclusion, the susceptibility of genetically modified mice to opportunistic infections has to be regarded with precaution, regardless of the type of genetic modification performed. Beside the classical opportunists, such as [Pasteurella] pneumotropica and Staphylococcus aureus, Escherichia coli should as well be closely monitored to evaluate whether it represents an emerging pathogen in the laboratory mouse.

Fine-Scale Genetic Structure of Monilinia fructicola During Brown Rot Epidemics Within Individual Peach Tree Canopies.

PubMed

Everhart, S E; Scherm, H

2015-04-01

The purpose of this study was to determine the fine-scale genetic structure of populations of the brown rot pathogen Monilinia fructicola within individual peach tree canopies to better understand within-tree plant pathogen diversity and to complement previous work on spatiotemporal development of brown rot disease at the canopy level. Across 3 years in a total of six trees, we monitored disease development, collected isolates from every M. fructicola symptom during the course of the season, and created high-resolution three-dimensional maps of all symptom and isolate locations within individual canopies using an electromagnetic digitizer. Each canopy population (65 to 173 isolates per tree) was characterized using a set of 13 microsatellite markers and analyzed for evidence of spatial genetic autocorrelation among isolates during the epidemic phase of the disease. Results showed high genetic diversity (average uh=0.529) and high genotypic diversity (average D=0.928) within canopies. The percentage of unique multilocus genotypes within trees was greater for blossom blight isolates (78.2%) than for fruit rot isolates (51.3%), indicating a greater contribution of clonal reproduction during the preharvest epidemic. For fruit rot isolates, between 54.2 and 81.7% of isolates were contained in one to four dominant clonal genotypes per tree having at least 10 members. All six fruit rot populations showed positive and significant spatial genetic autocorrelation for distance classes between 0.37 and 1.48 m. Despite high levels of within-tree pathogen diversity, the contribution of locally available inoculum combined with short-distance dispersal is likely the main factor generating clonal population foci and associated spatial genetic clustering within trees.

A Handheld Point-of-Care Genomic Diagnostic System

PubMed Central

Myers, Frank B.; Henrikson, Richard H.; Bone, Jennifer; Lee, Luke P.

2013-01-01

The rapid detection and identification of infectious disease pathogens is a critical need for healthcare in both developed and developing countries. As we gain more insight into the genomic basis of pathogen infectivity and drug resistance, point-of-care nucleic acid testing will likely become an important tool for global health. In this paper, we present an inexpensive, handheld, battery-powered instrument designed to enable pathogen genotyping in the developing world. Our Microfluidic Biomolecular Amplification Reader (µBAR) represents the convergence of molecular biology, microfluidics, optics, and electronics technology. The µBAR is capable of carrying out isothermal nucleic acid amplification assays with real-time fluorescence readout at a fraction of the cost of conventional benchtop thermocyclers. Additionally, the µBAR features cell phone data connectivity and GPS sample geotagging which can enable epidemiological surveying and remote healthcare delivery. The µBAR controls assay temperature through an integrated resistive heater and monitors real-time fluorescence signals from 60 individual reaction chambers using LEDs and phototransistors. Assays are carried out on PDMS disposable microfluidic cartridges which require no external power for sample loading. We characterize the fluorescence detection limits, heater uniformity, and battery life of the instrument. As a proof-of-principle, we demonstrate the detection of the HIV-1 integrase gene with the µBAR using the Loop-Mediated Isothermal Amplification (LAMP) assay. Although we focus on the detection of purified DNA here, LAMP has previously been demonstrated with a range of clinical samples, and our eventual goal is to develop a microfluidic device which includes on-chip sample preparation from raw samples. The µBAR is based entirely around open source hardware and software, and in the accompanying online supplement we present a full set of schematics, bill of materials, PCB layouts, CAD drawings, and source code for the µBAR instrument with the goal of spurring further innovation toward low-cost genetic diagnostics. PMID:23936402

Magnetogenetics: Remote Control of Cellular Signaling with Magnetic Fields

NASA Astrophysics Data System (ADS)

Sauer, Jeremy P.

Means for temporally regulating gene expression and cellular activity are invaluable for elucidating the underlying physiological processes and have therapeutic implications. Here we report the development of a system for remote regulation of gene expression by low frequency radiowaves (RF) or by a static magnetic field. We accomplished this by first adding iron oxide nanoparticles - either exogenously or as genetically encoded ferritin/ferric oxyhydroxide particle. These particles have been designed with affinity to the plasma membrane ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) by a conjugated antibody. Application of a magnetic field stimulates the particle to gate the ion channel and this, in turn, initiates calcium-dependent transgene expression. We first demonstrated in vitro that TRPV1 can be actuated to cause calcium flux into the cell by directly applying a localized magnetic field. In mice expressing these genetically encoded components, application of external magnetic field caused remote stimulation of insulin transgene expression and significantly lowered blood glucose. In addition, we are investigating mechanisms by which iron oxide nanoparticles can absorb RF, and transduce this energy to cause channel opening. This robust, repeatable method for remote cellular regulation in vivo may ultimately have applications in basic science, as well as in technology and therapeutics.

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study.

PubMed

Olivares, Marta; Benítez-Páez, Alfonso; de Palma, Giada; Capilla, Amalia; Nova, Esther; Castillejo, Gemma; Varea, Vicente; Marcos, Ascensión; Garrote, José Antonio; Polanco, Isabel; Donat, Ester; Ribes-Koninckx, Carmen; Calvo, Carmen; Ortigosa, Luis; Palau, Francesc; Sanz, Yolanda

2018-04-19

Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

Identification of three extra-chromosomal replicons in Leptospira pathogenic strain and development of new shuttle vectors.

PubMed

Zhu, Weinan; Wang, Jin; Zhu, Yongzhang; Tang, Biao; Zhang, Yunyi; He, Ping; Zhang, Yan; Liu, Boyu; Guo, Xiaokui; Zhao, Guoping; Qin, Jinhong

2015-02-15

The genome of pathogenic Leptospira interrogans contains two chromosomes. Plasmids and prophages are known to play specific roles in gene transfer in bacteria and can potentially serve as efficient genetic tools in these organisms. Although plasmids and prophage remnants have recently been reported in Leptospira species, their characteristics and potential applications in leptospiral genetic transformation systems have not been fully evaluated. Three extrachromosomal replicons designated lcp1 (65,732 bp), lcp2 (56,757 bp), and lcp3 (54,986 bp) in the L. interrogans serovar Linhai strain 56609 were identified through whole genome sequencing. All three replicons were stable outside of the bacterial chromosomes. Phage particles were observed in the culture supernatant of 56609 after mitomycin C induction, and lcp3, which contained phage-related genes, was considered to be an inducible prophage. L. interrogans-Escherichia coli shuttle vectors, constructed with the predicted replication elements of single rep or rep combined with parAB loci from the three plasmids were shown to successfully transform into both saprophytic and pathogenic Leptospira species, suggesting an essential function for rep genes in supporting auto-replication of the plasmids. Additionally, a wide distribution of homologs of the three rep genes was identified in L. interrogans isolates, and correlation tests showed that the transformability of the shuttle vectors in L. interrogans isolates depended, to certain extent, on genetic compatibility between the rep sequences of both plasmid and host. Three extrachromosomal replicons co-exist in L. interrogans, one of which we consider to be an inducible prophage. The vectors constructed with the rep genes of the three replicons successfully transformed into saprophytic and pathogenic Leptospira species alike, but this was partly dependent on genetic compatibility between the rep sequences of both plasmid and host.

Footprints of Directional Selection in Wild Atlantic Salmon Populations: Evidence for Parasite-Driven Evolution?

PubMed Central

Zueva, Ksenia J.; Lumme, Jaakko; Veselov, Alexey E.; Kent, Matthew P.; Lien, Sigbjørn; Primmer, Craig R.

2014-01-01

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved. PMID:24670947

Footprints of directional selection in wild Atlantic salmon populations: evidence for parasite-driven evolution?

PubMed

Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Lien, Sigbjørn; Primmer, Craig R

2014-01-01

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved.

Development of genetic techniques for the psychrotrophic fish pathogen Flavobacterium psychrophilum.

PubMed

Alvarez, B; Secades, P; McBride, M J; Guijarro, J A

2004-01-01

Flavobacterium psychrophilum, a member of the Cytophaga-Flavobacterium-Bacteroides group, is an important pathogen of salmonid fish. Previous attempts to develop genetic techniques for this fastidious, psychrotrophic bacterium have met with failure. Here we describe the development of techniques for the genetic manipulation of F. psychrophilum and the identification of plasmids, selectable markers, a reporter system, and a transposon that function in several isolates of this fish pathogen. The antibiotic resistance genes ermF, cfxA, and tetQ function in F. psychrophilum. Cloning vectors based on the F. psychrophilum cryptic plasmid pCP1 which carried these selectable markers were introduced by conjugation from E. coli, resulting in antibiotic-resistant colonies of F. psychrophilum. Conjugative transfer of DNA into F. psychrophilum was strain dependent. Efficient transfer was observed for two of the seven strains tested (THC02-90 and THC04-90). E. coli lacZY functioned in F. psychrophilum when expressed from a pCP1 promoter, allowing its development as a reporter for studies of gene expression. Plasmids isolated from F. psychrophilum were efficiently introduced into F. psychrophilum by electroporation, but plasmids isolated from E. coli were not suitable for transfer by this route, suggesting the presence of a restriction barrier. DNA isolated from F. psychrophilum was resistant to digestion by Sau3AI and BamHI, indicating that a Sau3AI-like restriction modification system may constitute part of this barrier. Tn4351 was introduced into F. psychrophilum from E. coli and transposed with apparent randomness, resulting in erythromycin-resistant colonies. The techniques developed in this study allow for genetic manipulation and analysis of this important fish pathogen.

Genomic analysis identifies masqueraders of full-term cerebral palsy.

PubMed

Takezawa, Yusuke; Kikuchi, Atsuo; Haginoya, Kazuhiro; Niihori, Tetsuya; Numata-Uematsu, Yurika; Inui, Takehiko; Yamamura-Suzuki, Saeko; Miyabayashi, Takuya; Anzai, Mai; Suzuki-Muromoto, Sato; Okubo, Yukimune; Endo, Wakaba; Togashi, Noriko; Kobayashi, Yasuko; Onuma, Akira; Funayama, Ryo; Shirota, Matsuyuki; Nakayama, Keiko; Aoki, Yoko; Kure, Shigeo

2018-05-01

Cerebral palsy is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested genetic diseases can be misdiagnosed as cerebral palsy. We hypothesized that two simple criteria, that is, full-term births and nonspecific brain MRI findings, are keys to extracting masqueraders among cerebral palsy cases due to the following: (1) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of cerebral palsy and (2) brain MRI assessment is essential for excluding environmental causes and other particular disorders. A total of 107 patients-all full-term births-without specific findings on brain MRI were identified among 897 patients diagnosed with cerebral palsy who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole-exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines. Pathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1 , CYP2U1 , SPAST , GNAO1 , CACNA1A , AMPD2 , STXBP1 , and SCN2A . Five identified variants had previously been reported. No pathogenic copy number variations were identified. The AMPD2 missense variant and the splice-site variants in CTNNB1 and AMPD2 were validated by in vitro functional experiments. The high rate of detecting causative genetic variants (52.9%) suggests that patients diagnosed with cerebral palsy in full-term births without specific MRI findings may include genetic diseases masquerading as cerebral palsy.

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

A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

USDA-ARS?s Scientific Manuscript database

This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

Genomic diagnosis for children with intellectual disability and/or developmental delay.

PubMed

Bowling, Kevin M; Thompson, Michelle L; Amaral, Michelle D; Finnila, Candice R; Hiatt, Susan M; Engel, Krysta L; Cochran, J Nicholas; Brothers, Kyle B; East, Kelly M; Gray, David E; Kelley, Whitley V; Lamb, Neil E; Lose, Edward J; Rich, Carla A; Simmons, Shirley; Whittle, Jana S; Weaver, Benjamin T; Nesmith, Amy S; Myers, Richard M; Barsh, Gregory S; Bebin, E Martina; Cooper, Gregory M

2017-05-30

Developmental disabilities have diverse genetic causes that must be identified to facilitate precise diagnoses. We describe genomic data from 371 affected individuals, 309 of which were sequenced as proband-parent trios. Whole-exome sequences (WES) were generated for 365 individuals (127 affected) and whole-genome sequences (WGS) were generated for 612 individuals (244 affected). Pathogenic or likely pathogenic variants were found in 100 individuals (27%), with variants of uncertain significance in an additional 42 (11.3%). We found that a family history of neurological disease, especially the presence of an affected first-degree relative, reduces the pathogenic/likely pathogenic variant identification rate, reflecting both the disease relevance and ease of interpretation of de novo variants. We also found that improvements to genetic knowledge facilitated interpretation changes in many cases. Through systematic reanalyses, we have thus far reclassified 15 variants, with 11.3% of families who initially were found to harbor a VUS and 4.7% of families with a negative result eventually found to harbor a pathogenic or likely pathogenic variant. To further such progress, the data described here are being shared through ClinVar, GeneMatcher, and dbGaP. Our data strongly support the value of large-scale sequencing, especially WGS within proband-parent trios, as both an effective first-choice diagnostic tool and means to advance clinical and research progress related to pediatric neurological disease.

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

PubMed Central

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-01-01

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing. PMID:29348823

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

PubMed

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Genetics Home Reference: lattice corneal dystrophy type II

MedlinePlus

... lattice corneal dystrophy type II can have a facial expression that appears sad. Related Information What does it ... links) Children's Craniofacial Association: A Guide to Understanding Facial ... pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment. Hum Mol Genet. ...

Expression of chloroperoxidase from Pseudomonas pyrrocinia in tobacco plastids for fungal resistance

USDA-ARS?s Scientific Manuscript database

While genetic improvement of susceptible crop species may enhance resistance to microbial pathogens and facilitate reduced pesticide load, the possibility for transmission of novel genes to wild relatives has hampered acceptance of genetically modified (GM) crops in some markets. Chloroplast transf...

Virus evolution and transmission in an ever more connected world

PubMed Central

Pybus, Oliver G.; Tatem, Andrew J.; Lemey, Philippe

2015-01-01

The frequency and global impact of infectious disease outbreaks, particularly those caused by emerging viruses, demonstrate the need for a better understanding of how spatial ecology and pathogen evolution jointly shape epidemic dynamics. Advances in computational techniques and the increasing availability of genetic and geospatial data are helping to address this problem, particularly when both information sources are combined. Here, we review research at the intersection of evolutionary biology, human geography and epidemiology that is working towards an integrated view of spatial incidence, host mobility and viral genetic diversity. We first discuss how empirical studies have combined viral spatial and genetic data, focusing particularly on the contribution of evolutionary analyses to epidemiology and disease control. Second, we explore the interplay between virus evolution and global dispersal in more depth for two pathogens: human influenza A virus and chikungunya virus. We discuss the opportunities for future research arising from new analyses of human transportation and trade networks, as well as the associated challenges in accessing and sharing relevant spatial and genetic data. PMID:26702033

ATG16L1: A multifunctional susceptibility factor in Crohn disease

PubMed Central

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-01-01

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease. PMID:25906181

ATG16L1: A multifunctional susceptibility factor in Crohn disease.

PubMed

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-04-03

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.

Comparison of the physiological characteristics of transgenic insect-resistant cotton and conventional lines.

PubMed

Li, Xiaogang; Ding, Changfeng; Wang, Xingxiang; Liu, Biao

2015-03-04

The introduction of transgenic insect-resistant cotton into agricultural ecosystems has raised concerns regarding its ecological effects. Many studies have been conducted to compare the differences in characteristics between transgenic cotton and conventional counterparts. However, few studies have focused on the different responses of transgenic cotton to stress conditions, especially to the challenges of pathogens. The aim of this work is to determine the extent of variation in physiological characteristics between transgenic insect-resistant cotton and the conventional counterpart infected by cotton soil-borne pathogens. The results showed that the difference in genetic backgrounds is the main factor responsible for the effects on biochemical characteristics of transgenic cotton when incubating with cotton Fusarium oxysporum. However, genetic modification had a significantly greater influence on the stomatal structure of transgenic cotton than the effects of cotton genotypes. Our results highlight that the differences in genetic background and/or genetic modifications may introduce variations in physiological characteristics and should be considered to explore the potential unexpected ecological effects of transgenic cotton.

Characterization of Microsatellites in Pseudogymnoascus destructans for White-nose Syndrome Genetic Analysis.

PubMed

Drees, Kevin P; Parise, Katy L; Rivas, Stephanie M; Felton, Lindsey L; Puechmaille, Sébastien J; Keim, Paul; Foster, Jeffrey T

2017-10-01

Despite only emerging in the past decade, white-nose syndrome has become among the most devastating wildlife diseases known. The pathogenic fungus Pseudogymnoascus destructans infects hibernating bats and typically leads to high rates of mortality at hibernacula during winter in North America. We developed a set of genetic markers to better differentiate P. destructans isolates. We designed and successfully characterized these 23 microsatellite markers of P. destructans for use in disease ecology and epidemiology research. We validated these loci with DNA extracted from a collection of P. destructans isolates from the US and Canada, as well as from Europe (the likely introduction source based on currently available data). Genetic diversity calculated for each locus and for the multilocus panel as a whole indicates sufficient allelic diversity to differentiate among and between samples from both Europe and North America. Indices of genetic diversity indicate a loss of allelic diversity that is consistent with the recent introduction and rapid spread of an emerging pathogen.

Exceptions to the rule: case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes.

PubMed

Rosenthal, E T; Bowles, K R; Pruss, D; van Kan, A; Vail, P J; McElroy, H; Wenstrup, R J

2015-12-01

Based on current consensus guidelines and standard practice, many genetic variants detected in clinical testing are classified as disease causing based on their predicted impact on the normal expression or function of the gene in the absence of additional data. However, our laboratory has identified a subset of such variants in hereditary cancer genes for which compelling contradictory evidence emerged after the initial evaluation following the first observation of the variant. Three representative examples of variants in BRCA1, BRCA2 and MSH2 that are predicted to disrupt splicing, prematurely truncate the protein, or remove the start codon were evaluated for pathogenicity by analyzing clinical data with multiple classification algorithms. Available clinical data for all three variants contradicts the expected pathogenic classification. These variants illustrate potential pitfalls associated with standard approaches to variant classification as well as the challenges associated with monitoring data, updating classifications, and reporting potentially contradictory interpretations to the clinicians responsible for translating test outcomes to appropriate clinical action. It is important to address these challenges now as the model for clinical testing moves toward the use of large multi-gene panels and whole exome/genome analysis, which will dramatically increase the number of genetic variants identified. © 2015 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic effects of ELISA-based segregation for control of bacterial kidney disease in Chinook salmon (Oncorhynchus tshawytscha)

USGS Publications Warehouse

Hard, J.J.; Elliott, D.G.; Pascho, R.J.; Chase, D.M.; Park, L.K.; Winton, J.R.; Campton, D.E.

2006-01-01

We evaluated genetic variation in ability of Chinook salmon (Oncorhynchus tshawytscha) to resist two bacterial pathogens: Renibacterium salmoninarum, the agent of bacterial kidney disease (BKD), and Listonella anguillarum, an agent of vibriosis. After measuring R. salmoninarum antigen in 499 adults by enzyme-linked immunosorbent assay (ELISA), we mated each of 12 males with high or low antigen levels to two females with low to moderate levels and exposed subsets of their progeny to each pathogen separately. We found no correlation between R. salmoninarum antigen level in parents and survival of their progeny following pathogen exposure. We estimated high heritability for resistance to R. salmoninarum (survival h2 = 0.890 ?? 0.256 (mean ?? standard error)) independent of parental antigen level, but low heritability for resistance to L. anguillarum (h2 = 0.128 ?? 0.078). The genetic correlation between these survivals (rA = -0.204 ?? 0.309) was near zero. The genetic and phenotypic correlations between survival and antigen levels among surviving progeny exposed to R. salmoninarum were both negative (rA = -0.716 ?? 0.140; rP = -0.378 ?? 0.041), indicating that variation in antigen level is linked to survival. These results suggest that selective culling of female broodstock with high antigen titers, which is effective in controlling BKD in salmon hatcheries, will not affect resistance of their progeny. ?? 2006 NRC.

Molecular Genetics of Beauveria bassiana Infection of Insects.

PubMed

Ortiz-Urquiza, A; Keyhani, N O

2016-01-01

Research on the insect pathogenic filamentous fungus, Beauveria bassiana has witnessed significant growth in recent years from mainly physiological studies related to its insect biological control potential, to addressing fundamental questions regarding the underlying molecular mechanisms of fungal development and virulence. This has been in part due to a confluence of robust genetic tools and genomic resources for the fungus, and recognition of expanded ecological interactions with which the fungus engages. Beauveria bassiana is a broad host range insect pathogen that has the ability to form intimate symbiotic relationships with plants. Indeed, there is an increasing realization that the latter may be the predominant environmental interaction in which the fungus participates, and that insect parasitism may be an opportunist lifestyle evolved due to the carbon- and nitrogen-rich resources present in insect bodies. Here, we will review progress on the molecular genetics of B. bassiana, which has largely been directed toward identifying genetic pathways involved in stress response and virulence assumed to have practical applications in improving the insect control potential of the fungus. Important strides have also been made in understanding aspects of B. bassiana development. Finally, although increasingly apparent in a number of studies, there is a need for progressing beyond phenotypic mutant characterization to sufficiently investigate the molecular mechanisms underlying B. bassiana's unique and diverse lifestyles as saprophyte, insect pathogen, and plant mutualist. Copyright © 2016 Elsevier Inc. All rights reserved.

The challenges and promises of genetic approaches for ballast water management

NASA Astrophysics Data System (ADS)

Rey, Anaïs; Basurko, Oihane C.; Rodríguez-Ezpeleta, Naiara

2018-03-01

Ballast water is a main vector of introduction of Harmful Aquatic Organisms and Pathogens, which includes Non-Indigenous Species. Numerous and diversified organisms are transferred daily from a donor to a recipient port. Developed to prevent these introduction events, the International Convention for the Control and Management of Ships' Ballast Water and Sediments will enter into force in 2017. This international convention is asking for the monitoring of Harmful Aquatic Organisms and Pathogens. In this review, we highlight the urgent need to develop cost-effective methods to: (1) perform the biological analyses required by the convention; and (2) assess the effectiveness of two main ballast water management strategies, i.e. the ballast water exchange and the use of ballast water treatment systems. We have compiled the biological analyses required by the convention, and performed a comprehensive evaluation of the potential and challenges of the use of genetic tools in this context. Following an overview of the studies applying genetic tools to ballast water related research, we present metabarcoding as a relevant approach for early detection of Harmful Aquatic Organisms and Pathogens in general and for ballast water monitoring and port risk assessment in particular. Nonetheless, before implementation of genetic tools in the context of the ballast water management convention, benchmarked tests against traditional methods should be performed, and standard, reproducible and easy to apply protocols should be developed.

RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism

PubMed Central

Soueid, Jihane; Kourtian, Silva; Makhoul, Nadine J.; Makoukji, Joelle; Haddad, Sariah; Ghanem, Simona S.; Kobeissy, Firas; Boustany, Rose-Mary

2016-01-01

Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders characterized by ritualistic-repetitive behaviors and impaired verbal and non-verbal communication. Objectives were to determine the contribution of genetic variation to ASDs in the Lebanese. Affymetrix Cytogenetics Whole-Genome 2.7 M and CytoScan™ HD Arrays were used to detect CNVs in 41 Lebanese autistic children and 35 non-autistic, developmentally delayed and intellectually disabled patients. 33 normal participants were used as controls. 16 de novo CNVs and 57 inherited CNVs, including recognized pathogenic 16p11.2 duplications and 2p16.3 deletions were identified. A duplication at 1q43 classified as likely pathogenic encompasses RYR2 as a potential ASD candidate gene. This previously identified CNV has been classified as both pathogenic, and, of uncertain significance. A duplication of unknown significance at 10q11.22, proposed as a modulator for phenotypic disease expression in Rett syndrome, was also identified. The novel potential autism susceptibility genes PTDSS1 and AREG were uncovered and warrant further genetic and functional analyses. Previously described and novel genetic targets in ASD were identified in Lebanese families with autism. These findings may lead to improved diagnosis of ASDs and informed genetic counseling, and may also lead to untapped therapeutic targets applicable to Lebanese and non-Lebanese patients. PMID:26742492

Characterization of Ascochyta rabiei for population structure, mating type and pathogenic variability from Pakistan and United States

USDA-ARS?s Scientific Manuscript database

Chickpea production is greatly hampered by blight causing fungal pathogen Ascochyta rabiei (AR) in chickpea growing regions of the world. Genetic variability and mating type frequency of thirty-two AR isolates from six geographical regions of Pakistan were compared with a US-AR population. Pakistani...

Biotechnology: Genetically Engineered Pathogens (The Counterproliferation Papers, Future Warfare Series No. 53)

DTIC Science & Technology

2010-06-01

ENGINEERED PATHOGENS ....... 8 Binary biological weapons ...the crossroads of radicalism and technology. When the spread of chemical and biological and nuclear weapons , along with ballistic missile...and individuals, given the opportunity to employ biological weapons , will most likely use it to inflict harm and terror on the United States and its

Infection of Brachypodium distachyon by formae speciales of Puccinia graminis: early infection events and host-pathogen incompatibility

USDA-ARS?s Scientific Manuscript database

Brachypodium distachyon is an emerging model to study fungal disease resistance in cereals and grasses. We characterized the stem rust-Brachypodium pathosystem to evaluate its potential for investigating molecular and genetic aspects of resistance to P. graminis, the pathogen that causes stem rust. ...

Genetic diversity of the myrtle rust pathogen (Austropuccinia psidii) in the Americas and Hawaii: Global implications for invasive threat assessments

Treesearch

J. E. Stewart; A.L. Ross-Davis; R. N. Graҫa; A. C. Alfenas; T. L. Peever; J. W. Hanna; J. Y. Uchida; R. D. Hauff; C. Y. Kadooka; M.-S. Kim; P. G. Cannon; S. Namba; S. Simeto; C. A. Pérez; M. B. Rayamajhi; D.J. Lodge; M. Arguedas; R. Medel-Ortiz; M. A. López-Ramirez; P. Tennant; M. Glen; P. S. Machado; A. R. McTaggart; A. J. Carnegie; N. B. Klopfenstein; M. Cleary

2017-01-01

Since the myrtle rust pathogen (Austropuccinia psidii) was first reported (as Puccinia psidii) in Brazil on guava (Psidium guajava) in 1884, it has been found infecting diverse myrtaceous species. Because A. psidii has recently spread rapidly worldwide with an extensive host range,...

Factors influencing plant regeneration from seedling explants of Hairy nightshade (Solanum sarrachoides)

USDA-ARS?s Scientific Manuscript database

A good model plant to investigate plant – pathogen interactions would be easy to grow, have a short life cycle, be a natural host of many pathogens, and be easy to manipulate genetically. Hairy nightshade (Solanum sarrachoides) is a ubiquitous, fast growing weed that produces copious amounts of see...

Integrating concepts of landscape ecology with the molecular biology of forest pathogens

Treesearch

John E. Lundquist; Ned B. Klopfenstein

2001-01-01

Increasingly more research has focused on characterizing diversity within forest pathogen populations using molecular markers but few studies have characterized features of the landscape that help create or maintain this diversity. Forest diseases commonly occur in patchy distributions across natural landscapes which can be reflected in the genetic composition of the...

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

USDA-ARS?s Scientific Manuscript database

During the last decade, a combination of molecular surveillance and population genetic analyses have significantly altered our understanding of Fusarium graminearum, the major FHB pathogen in North America. In addition to the native NA1 population (largely 15ADON toxin type) and the invasive NA2 pop...

Quantitative trait loci for resistance to two fungal pathogens in Quercus robur

Treesearch

Cécile Robin; Amira Mougou-Hamdane; Jean-Marc Gion; Antoine Kremer; Marie-Laure Desprez-Loustau

2012-01-01

Powdery mildew, caused by Erysiphe alphitoides (Ascomycete), is the most frequent disease of oaks, which are also known to be host plants for Phytophthora cinnamomi (Oomycete), the causal agent of ink disease. Components of genetic resistance to these two pathogens, infecting either leaves or root and collar, were...

Secreted Gaussia princeps luciferase as a reporter of Escherichia coli replication in a mouse tissue cage model of infection.

PubMed

Liu, Mingyu; Blinn, Christina; McLeod, Sarah M; Wiseman, John W; Newman, Joseph V; Fisher, Stewart L; Walkup, Grant K

2014-01-01

Measurement of bacterial burden in animal infection models is a key component for both bacterial pathogenesis studies and therapeutic agent research. The traditional quantification means for in vivo bacterial burden requires frequent animal sacrifice and enumerating colony forming units (CFU) recovered from infection loci. To address these issues, researchers have developed a variety of luciferase-expressing bacterial reporter strains to enable bacterial detection in living animals. To date, all such luciferase-based bacterial reporters are in cell-associated form. Production of luciferase-secreting recombinant bacteria could provide the advantage of reporting CFU from both infection loci themselves and remote sampling (eg. body fluid and plasma). Toward this end, we have genetically manipulated a pathogenic Escherichia coli (E. coli) strain, ATCC25922, to secrete the marine copepod Gaussia princeps luciferase (Gluc), and assessed the use of Gluc as both an in situ and ex situ reporter for bacterial burden in mouse tissue cage infections. The E. coli expressing Gluc demonstrates in vivo imaging of bacteria in a tissue cage model of infection. Furthermore, secreted Gluc activity and bacterial CFUs recovered from tissue cage fluid (TCF) are correlated along 18 days of infection. Importantly, secreted Gluc can also be detected in plasma samples and serve as an ex situ indicator for the established tissue cage infection, once high bacterial burdens are achieved. We have demonstrated that Gluc from marine eukaryotes can be stably expressed and secreted by pathogenic E. coli in vivo to enable a facile tool for longitudinal evaluation of persistent bacterial infection.

Insights From Natural Host-Parasite Interactions: The Drosophila Model

PubMed Central

Keebaugh, Erin S.; Schlenke, Todd A.

2013-01-01

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

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

Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans

PubMed Central

Pradel, Elizabeth; Zhang, Yun; Pujol, Nathalie; Matsuyama, Tohey; Bargmann, Cornelia I.; Ewbank, Jonathan J.

2007-01-01

The nematode Caenorhabditis elegans is present in soils and composts, where it can encounter a variety of microorganisms. Some bacteria in these rich environments are innocuous food sources for C. elegans, whereas others are pathogens. Under laboratory conditions, C. elegans will avoid certain pathogens, such as Serratia marcescens, by exiting a bacterial lawn a few hours after entering it. By combining bacterial genetics and nematode genetics, we show that C. elegans specifically avoids certain strains of Serratia based on their production of the cyclic lipodepsipentapeptide serrawettin W2. Lawn-avoidance behavior is chiefly mediated by the two AWB chemosensory neurons, probably through G protein-coupled chemoreceptors, and also involves the nematode Toll-like receptor gene tol-1. Purified serrawettin W2, added to an Escherichia coli lawn, can directly elicit lawn avoidance in an AWB-dependent fashion, as can another chemical detected by AWB. These findings represent an insight into chemical recognition between these two soil organisms and reveal sensory mechanisms for pathogen recognition in C. elegans. PMID:17267603

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).

Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species

DOE PAGES

Kjerbolling, Inge; Vesth, Tammi C.; Frisvad, Jens C.; ...

2018-01-09

The fungal genus of Aspergillus is highly interesting, containing everything from industrial cell factories over model organisms to human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse Aspergillus species (A. campestris, A. novofumigatus, A. ochraceoroseus and A. steynii) has been whole genome PacBio sequenced to provide genetic references in three Aspergillus sections. Additionally, A. taichungensis and A. candidus were sequenced for SM elucidation. Thirteen Aspergillus genomes were analysed with comparative genomics to determine phylogeny and genetic diversity, showing that each new genome contains 15–27% genes not found in othermore » sequenced Aspergilli. In particular, the new species A. novofumigatus was compared to the pathogenic species A. fumigatus. This suggests that A. novofumigatus can produce most of the same allergens, virulence and pathogenicity factors as A. fumigatus suggesting that A. novofumigatus could be as pathogenic as A. fumigatus. Furthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences and predictive algorithms.« less

Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species

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

Kjerbolling, Inge; Vesth, Tammi C.; Frisvad, Jens C.

The fungal genus of Aspergillus is highly interesting, containing everything from industrial cell factories over model organisms to human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse Aspergillus species (A. campestris, A. novofumigatus, A. ochraceoroseus and A. steynii) has been whole genome PacBio sequenced to provide genetic references in three Aspergillus sections. Additionally, A. taichungensis and A. candidus were sequenced for SM elucidation. Thirteen Aspergillus genomes were analysed with comparative genomics to determine phylogeny and genetic diversity, showing that each new genome contains 15–27% genes not found in othermore » sequenced Aspergilli. In particular, the new species A. novofumigatus was compared to the pathogenic species A. fumigatus. This suggests that A. novofumigatus can produce most of the same allergens, virulence and pathogenicity factors as A. fumigatus suggesting that A. novofumigatus could be as pathogenic as A. fumigatus. Furthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences and predictive algorithms.« less

Pathogenic Mechanisms and In Vitro Diagnosis of AERD

PubMed Central

Schäfer, Dirk; Maune, Steffen

2012-01-01

Aspirin-exacerbated respiratory disease (AERD) refers to chronic rhinosinusitis, nasal polyposis, bronchoconstriction, and/or eosinophilic inflammation in asthmatics following the exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A key pathogenic mechanism associated with AERD is the imbalance of eicosanoid metabolism focusing on prostanoid and leukotriene pathways in airway mucosa as well as blood cells. Genetic and functional metabolic studies on vital and non-vital cells pointed to the variability and the crucial role of lipid mediators in disease susceptibility and their response to medication. Eicosanoids, exemplified by prostaglandin E2 (PGE2) and peptidoleukotrienes (pLT), are potential metabolic biomarkers contributing to the AERD phenotype. Also other mediators are implicated in the progress of AERD. Considering the various pathogenic mechanisms of AERD, a multitude of metabolic and genetic markers is suggested to be implicated and were introduced as potential biomarkers for in vitro diagnosis during the past decades. Deduced from an eicosanoid-related pathogenic mechanism, functional tests balancing PGE2 and pLT as well as other eicosanoids from preferentially vital leukocytes demonstrated their applicability for in vitro diagnosis of AERD. PMID:22654920

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

PubMed Central

Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J.; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Vecchio, Lucia Del; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J.; Novak, Jan; Julian, Bruce A.; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P.; Gharavi, Ali G.

2014-01-01

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

[The detection of occurrence rate of genes coding capability to form pili binding in auto-strains of Escherichia coli].

PubMed

Ivanova, E I; Popkova, S M; Dzhioev, Iu P; Rakova, E B; Dolgikh, V V; Savel'kaeva, M V; Nemchenko, U M; Bukharova, E V; Serdiuk, L V

2015-01-01

E. coli is a commensal of intestine of the vertebrata. The exchange of genetic material of different types of bacteria between themselves and with other representatives of family of Enterobacteriaceae in intestinal ecosystem results in development of types of normal colibacillus with genetic characteristics of pathogenicity that can serve as a theoretical substantiation to attribute such strains to pathobionts. The entero-pathogenic colibacillus continues be an important cause of diarrhea in children in developing countries. The gene responsible for formation of pili binding is a necessary condition for virulence of entero-pathogenic colibacillus. The polymerase chain reaction was applied to examine 316 strains of different types of E. coli (normal, with weak enzyme activity and hemolytic activity) isolated from healthy children and children with functional disorders of gastro-intestinal tract for presence of genes coding capability to form pill binding. The presence of this gene in different biochemical types of E. coli permits to establish the fact of formation of reservoir of pathogenicity in indigent microbiota of intestinal biocenosis.

Natural Competence and Recombination in the Plant Pathogen Xylella fastidiosa ▿

PubMed Central

Kung, Stephanie H.; Almeida, Rodrigo P. P.

2011-01-01

Homologous recombination is one of many forces contributing to the diversity, adaptation, and emergence of pathogens. For naturally competent bacteria, transformation is one possible route for the acquisition of novel genetic material. This study demonstrates that Xylella fastidiosa, a generalist bacterial plant pathogen responsible for many emerging plant diseases, is naturally competent and able to homologously recombine exogenous DNA into its genome. Several factors that affect transformation and recombination efficiencies, such as nutrient availability, growth stage, and methylation of transforming DNA, were identified. Recombination was observed in at least one out of every 106 cells when exogenous plasmid DNA was supplied and one out of every 107 cells when different strains were grown together in vitro. Based on previous genomic studies and experimental data presented here, there is mounting evidence that recombination can occur at relatively high rates and could play a large role in shaping the genetic diversity of X. fastidiosa. PMID:21666009

Geometry correction Algorithm for UAV Remote Sensing Image Based on Improved Neural Network

NASA Astrophysics Data System (ADS)

Liu, Ruian; Liu, Nan; Zeng, Beibei; Chen, Tingting; Yin, Ninghao

2018-03-01

Aiming at the disadvantage of current geometry correction algorithm for UAV remote sensing image, a new algorithm is proposed. Adaptive genetic algorithm (AGA) and RBF neural network are introduced into this algorithm. And combined with the geometry correction principle for UAV remote sensing image, the algorithm and solving steps of AGA-RBF are presented in order to realize geometry correction for UAV remote sensing. The correction accuracy and operational efficiency is improved through optimizing the structure and connection weight of RBF neural network separately with AGA and LMS algorithm. Finally, experiments show that AGA-RBF algorithm has the advantages of high correction accuracy, high running rate and strong generalization ability.

Effects of pathogen exposure on life history variation in the gypsy moth (Lymantria dispar)

PubMed Central

Páez, David J.; Fleming-Davies, Arietta E.; Dwyer, Greg

2015-01-01

Investment in host defenses against pathogens may lead to tradeoffs with host fecundity. When such tradeoffs arise from genetic correlations, rates of phenotypic change by natural selection may be affected. However, genetic correlations between host survival and fecundity are rarely quantified. To understand tradeoffs between immune responses to baculovirus exposure and fecundity in the gypsy moth (Lymantria dispar), we estimated genetic correlations between survival probability and traits related to fecundity, such as pupal weight. In addition, we tested whether different virus isolates have different effects on male and female pupal weight. To estimate genetic correlations, we exposed individuals of known relatedness to a single baculovirus isolate. To then evaluate the effect of virus isolate on pupal weight, we exposed a single gypsy moth strain to 16 baculovirus isolates. We found a negative genetic correlation between survival and pupal weight. In addition, virus exposure caused late-pupating females to be identical in weight to males, whereas unexposed females were 2–3 times as large as unexposed males. Finally, we found that female pupal weight is a quadratic function of host mortality across virus isolates, which is likely due to tradeoffs and compensatory growth processes acting at high and low mortality levels, respectively. Overall, our results suggest that fecundity costs may strongly affect the response to selection for disease resistance. In nature, baculoviruses contribute to the regulation of gypsy moth outbreaks, as pathogens often do in forest-defoliating insects. We therefore argue that tradeoffs between host life-history traits may help explain outbreak dynamics. PMID:26201381

Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport Syndrome.

PubMed

Funk, Steven D; Bayer, Raymond H; Malone, Andrew F; McKee, Karen K; Yurchenco, Peter D; Miner, Jeffrey H

2018-03-01

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β 2 ( LAMB2 ), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient's nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3 -/- mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5 +/- females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α 3 α 4 α 5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans. Copyright © 2018 by the American Society of Nephrology.

Pathogenicity for onion and genetic diversity of isolates of the pathogenic fungus Colletotrichum gloeosporioides (Phyllachoraceae) from the State of Pernambuco, Brazil.

PubMed

Nova, M X Vila; Borges, L R; de Sousa, A C B; Brasileiro, B T R V; Lima, E A L A; da Costa, A F; de Oliveira, N T

2011-02-22

Onion anthracnose, caused by Colletotrichum gloeosporioides, is one of the main diseases of onions in the State of Pernambuco. We examined the pathogenicity of 15 C. gloeosporioides strains and analyzed their genetic variability using RAPDs and internal transcribed spacers (ITS) of the rDNA region. Ten of the strains were obtained from substrates and hosts other than onion, including chayote (Sechium edule), guava (Psidium guajava), pomegranate (Punica granatum), water from the Capibaribe River, maracock (Passiflora sp), coconut (Cocus nucifera), surinam cherry (Eugenia uniflora), and marine soil; five isolates came from onions collected from four different regions of the State of Pernambuco and one region of the State of Amazonas. Pathogenicity tests were carried out using onion leaves and bulbs. All strains were capable of causing disease in leaves, causing a variable degree of lesions on the leaves; four strains caused the most severe damage. In the onion bulb tests, only three of the above strains caused lesions. Seven primers of arbitrary sequences were used in the RAPD analysis, generating polymorphic bands that allowed the separation of the strains into three distinct groups. The amplification products generated with the primers ITS1 and ITS4 also showed polymorphism when digested with three restriction enzymes, DraI, HaeIII and MspI. Only the latter two demonstrated genetic variations among the strains. These two types of molecular markers were able to differentiate the strain from the State of Amazonas from those of the State of Pernambuco. However, there was no relationship between groups of strains, based on molecular markers, and degree of pathogenicity for onion leaves and bulbs.

Genetic characterisation of novel, highly pathogenic avian influenza (HPAI) H5N6 viruses isolated in birds, South Korea, November 2016

PubMed Central

Si, Young-Jae; Lee, In Won; Kim, Eun-Ha; Kim, Young-Il; Kwon, Hyeok-Il; Park, Su-Jin; Nguyen, Hiep Dinh; Kim, Se Mi; Kwon, Jin-Jung; Choi, Won-Suk; Beak, Yun Hee; Song, Min-Suk; Kim, Chul-Joong; Webby, Richard J.; Choi, Young-Ki

2017-01-01

A novel genotype of H5N6 influenza viruses was isolated from migratory birds in South Korea during November 2016. Domestic outbreaks of this virus were associated with die-offs of wild birds near reported poultry cases in Chungbuk province, central South Korea. Genetic analysis and animal studies demonstrated that the Korean H5N6 viruses are highly pathogenic avian influenza (HPAI) viruses and that these viruses are novel reassortants of at least three different subtypes (H5N6, H4N2 and H1N1). PMID:28079520

Immunogenetic Variation and Differential Pathogen Exposure in Free-Ranging Cheetahs across Namibian Farmlands

PubMed Central

Castro-Prieto, Aines; Wachter, Bettina; Melzheimer, Joerg; Thalwitzer, Susanne; Hofer, Heribert; Sommer, Simone

2012-01-01

Background Genes under selection provide ecologically important information useful for conservation issues. Major histocompatibility complex (MHC) class I and II genes are essential for the immune defence against pathogens from intracellular (e.g. viruses) and extracellular (e.g. helminths) origins, respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed higher exposure to viral pathogens in individuals from north-central than east-central regions. Here we examined whether the observed differences in exposure to viruses influence the patterns of genetic variation and differentiation at MHC loci in 88 free-ranging Namibian cheetahs. Methodology/Principal Findings Genetic variation at MHC I and II loci was assessed through single-stranded conformation polymorphism (SSCP) analysis and sequencing. While the overall allelic diversity did not differ, we observed a high genetic differentiation at MHC class I loci between cheetahs from north-central and east-central Namibia. No such differentiation in MHC class II and neutral markers were found. Conclusions/Significance Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species. PMID:23145096

Immunogenetic variation and differential pathogen exposure in free-ranging cheetahs across Namibian farmlands.

PubMed

Castro-Prieto, Aines; Wachter, Bettina; Melzheimer, Joerg; Thalwitzer, Susanne; Hofer, Heribert; Sommer, Simone

2012-01-01

Genes under selection provide ecologically important information useful for conservation issues. Major histocompatibility complex (MHC) class I and II genes are essential for the immune defence against pathogens from intracellular (e.g. viruses) and extracellular (e.g. helminths) origins, respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed higher exposure to viral pathogens in individuals from north-central than east-central regions. Here we examined whether the observed differences in exposure to viruses influence the patterns of genetic variation and differentiation at MHC loci in 88 free-ranging Namibian cheetahs. Genetic variation at MHC I and II loci was assessed through single-stranded conformation polymorphism (SSCP) analysis and sequencing. While the overall allelic diversity did not differ, we observed a high genetic differentiation at MHC class I loci between cheetahs from north-central and east-central Namibia. No such differentiation in MHC class II and neutral markers were found. Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species.

Flexible nanopillar-based electrochemical sensors for genetic detection of foodborne pathogens

NASA Astrophysics Data System (ADS)

Park, Yoo Min; Lim, Sun Young; Jeong, Soon Woo; Song, Younseong; Bae, Nam Ho; Hong, Seok Bok; Choi, Bong Gill; Lee, Seok Jae; Lee, Kyoung G.

2018-06-01

Flexible and highly ordered nanopillar arrayed electrodes have brought great interest for many electrochemical applications, especially to the biosensors, because of its unique mechanical and topological properties. Herein, we report an advanced method to fabricate highly ordered nanopillar electrodes produced by soft-/photo-lithography and metal evaporation. The highly ordered nanopillar array exhibited the superior electrochemical and mechanical properties in regard with the wide space to response with electrolytes, enabling the sensitive analysis. As-prepared gold and silver electrodes on nanopillar arrays exhibit great and stable electrochemical performance to detect the amplified gene from foodborne pathogen of Escherichia coli O157:H7. Additionally, lightweight, flexible, and USB-connectable nanopillar-based electrochemical sensor platform improves the connectivity, portability, and sensitivity. Moreover, we successfully confirm the performance of genetic analysis using real food, specially designed intercalator, and amplified gene from foodborne pathogens with high reproducibility (6% standard deviation) and sensitivity (10 × 1.01 CFU) within 25 s based on the square wave voltammetry principle. This study confirmed excellent mechanical and chemical characteristics of nanopillar electrodes have a great and considerable electrochemical activity to apply as genetic biosensor platform in the fields of point-of-care testing (POCT).

Bacillus thuringiensis Is an Environmental Pathogen and Host-Specificity Has Developed as an Adaptation to Human-Generated Ecological Niches

PubMed Central

Argôlo-Filho, Ronaldo Costa; Loguercio, Leandro Lopes

2013-01-01

Bacillus thuringiensis (Bt) has been used successfully as a biopesticide for more than 60 years. More recently, genes encoding their toxins have been used to transform plants and other organisms. Despite the large amount of research on this bacterium, its true ecology is still a matter of debate, with two major viewpoints dominating: while some understand Bt as an insect pathogen, others see it as a saprophytic bacteria from soil. In this context, Bt’s pathogenicity to other taxa and the possibility that insects may not be the primary targets of Bt are also ideas that further complicate this scenario. The existence of conflicting research results, the difficulty in developing broader ecological and genetics studies, and the great genetic plasticity of this species has cluttered a definitive concept. In this review, we gathered information on the aspects of Bt ecology that are often ignored, in the attempt to clarify the lifestyle, mechanisms of transmission and target host range of this bacterial species. As a result, we propose an integrated view to account for Bt ecology. Although Bt is indeed a pathogenic bacterium that possesses a broad arsenal for virulence and defense mechanisms, as well as a wide range of target hosts, this seems to be an adaptation to specific ecological changes acting on a versatile and cosmopolitan environmental bacterium. Bt pathogenicity and host-specificity was favored evolutionarily by increased populations of certain insect species (or other host animals), whose availability for colonization were mostly caused by anthropogenic activities. These have generated the conditions for ecological imbalances that favored dominance of specific populations of insects, arachnids, nematodes, etc., in certain areas, with narrower genetic backgrounds. These conditions provided the selective pressure for development of new hosts for pathogenic interactions, and so, host specificity of certain strains. PMID:26462580

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

PubMed

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

2016-01-01

The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes

PubMed Central

May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M. Arfan; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G.; Cilio, Maria Roberta; Kunz, Wolfram S.; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R.; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A.

2016-01-01

Objective The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10−4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions. PMID:26990884

Genetic basis of destruxin production in the entomopathogen Metarhizium robertsii

USDA-ARS?s Scientific Manuscript database

Destruxins are among the most exhaustively researched secondary metabolites of entomopathogenic fungi, yet definitive evidence for their roles in pathogenicity and virulence has yet to be shown. To establish the genetic bases for the biosynthesis of this family of depsipeptides, we identified a 23,7...

Genetic characterization of resistance to Sclerotinia in lettuce cultivar Eruption

USDA-ARS?s Scientific Manuscript database

Lettuce drop caused by the fungal pathogens Sclerotinia minor and S. sclerotiorum is a serious disease of lettuce. The use of genetic resistance as part of an integrated lettuce drop management strategy should have a significant economic advantage in mitigating yield loss. Sclerotinia resistance is ...

Ancestral seed zones and genetic mixture of tanoak

Treesearch

Richard Dodd; Zara Rafii; Wasima Mayer

2010-01-01

Understanding the genetic structure of tanoak (Lithocarpus densiflorus) is necessary to pathologists seeking natural variation in resistance to Phytophthora ramorum, cause of sudden oak death (SOD), and to resource managers who need indications of conservation priorities for this species now threatened by this introduced pathogen. We investigated...

Advances in the genetic improvement of Prunus domestica utilizing genetic engineering

USDA-ARS?s Scientific Manuscript database

Plum producers world-wide are facing multiple challenges including climate change, reductions in available labor, the need for reduced chemical inputs, the spread of native and exotic pests and pathogens, and consumer demands for improved fruit quality and health benefits. Meeting these challenges ...

Genetic diversity and structure of Phakopsora pachyrhizi infecting soybean in Nigeria

USDA-ARS?s Scientific Manuscript database

The genetic structure of Nigerian field populations of the soybean rust pathogen Phakopsora pachyrhizi was determined using 18 simple sequence repeat markers. A total of 113 fungal isolates was collected by hierarchical sampling infected leaves from soybean fields in three agroecological zones in 2...

Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk for an Inherited Arrhythmia or Cardiomyopathy.

PubMed

Christian, Susan; Atallah, Joseph; Clegg, Robin; Giuffre, Michael; Huculak, Cathleen; Dzwiniel, Tara; Parboosingh, Jillian; Taylor, Sherryl; Somerville, Martin

2018-02-01

Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

Emerging pathogens in the fish farming industry and sequencing-based pathogen discovery.

PubMed

Tengs, Torstein; Rimstad, Espen

2017-10-01

The use of large scale DNA/RNA sequencing has become an integral part of biomedical research. Reduced sequencing costs and the availability of efficient computational resources has led to a revolution in how problems concerning genomics and transcriptomics are addressed. Sequencing-based pathogen discovery represents one example of how genetic data can now be used in ways that were previously considered infeasible. Emerging pathogens affect both human and animal health due to a multitude of factors, including globalization, a shifting environment and an increasing human population. Fish farming represents a relevant, interesting and challenging system to study emerging pathogens. This review summarizes recent progress in pathogen discovery using sequence data, with particular emphasis on viruses in Atlantic salmon (Salmo salar). Copyright © 2017 Elsevier Ltd. All rights reserved.

Adenovirus-based genetic vaccines for biodefense.

PubMed

Boyer, Julie L; Kobinger, Gary; Wilson, James M; Crystal, Ronald G

2005-02-01

The robust host responses elicited against transgenes encoded by (E1-)(E3-) adenovirus (Ad) gene transfer vectors can be used to develop Ad-based vectors as platform technologies for vaccines against potential bioterror pathogens. This review focuses on pathogens of major concern as bioterror agents and why Ad vectors are ideal as anti-bioterror vaccine platforms, providing examples from our laboratories of using Ad vectors as vaccines against potential bioterror pathogens and how Ad vectors can be developed to enhance vaccine efficacy in the bioterror war.

Hybrid selection for sequencing pathogen genomes from clinical samples

PubMed Central

2011-01-01

We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of human and Plasmodium falciparum malaria parasite DNA as well as clinical samples from infected patients, we demonstrate an average of approximately 40-fold enrichment of parasite DNA after hybrid selection. This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla. PMID:21835008

Disease Resistance in Atlantic Salmon (Salmo salar): Coinfection of the Intracellular Bacterial Pathogen Piscirickettsia salmonis and the Sea Louse Caligus rogercresseyi

PubMed Central

Lhorente, Jean Paul; Gallardo, José A.; Villanueva, Beatriz; Carabaño, María J.; Neira, Roberto

2014-01-01

Background Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. Methodology In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. Main Findings C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h 2 SI = 0.23±0.07; h 2 LC = 0.17±0.08; h 2 HC = 0.24±0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99±0.01) but not between the single and coinfection treatments (rg SI-LC = −0.14±0.33; rg SI-HC = 0.32±0.34). Conclusions/Significance C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation. PMID:24736323

Comparative Genomic Analysis Shows That Avian Pathogenic Escherichia coli Isolate IMT5155 (O2:K1:H5; ST Complex 95, ST140) Shares Close Relationship with ST95 APEC O1:K1 and Human ExPEC O18:K1 Strains

PubMed Central

Pan, Zihao; Hu, Lin; Wang, Shaohui; Wang, Haojin; Leung, Frederick C.; Dai, Jianjun; Fan, Hongjie

2014-01-01

Avian pathogenic E. coli and human extraintestinal pathogenic E. coli serotypes O1, O2 and O18 strains isolated from different hosts are generally located in phylogroup B2 and ST complex 95, and they share similar genetic characteristics and pathogenicity, with no or minimal host specificity. They are popular objects for the study of ExPEC genetic characteristics and pathogenesis in recent years. Here, we investigated the evolution and genetic blueprint of APEC pathotype by performing phylogenetic and comparative genome analysis of avian pathogenic E. coli strain IMT5155 (O2:K1:H5; ST complex 95, ST140) with other E. coli pathotypes. Phylogeny analyses indicated that IMT5155 has closest evolutionary relationship with APEC O1, IHE3034, and UTI89. Comparative genomic analysis showed that IMT5155 and APEC O1 shared significant genetic overlap/similarities with human ExPEC dominant O18:K1 strains (IHE3034 and UTI89). Furthermore, the unique PAI I5155 (GI-12) was identified and found to be conserved in APEC O2 serotype isolates. GI-7 and GI-16 encoding two typical T6SSs in IMT5155 might be useful markers for the identification of ExPEC dominant serotypes (O1, O2, and O18) strains. IMT5155 contained a ColV plasmid p1ColV5155, which defined the APEC pathotype. The distribution analysis of 10 sequenced ExPEC pan-genome virulence factors among 47 sequenced E. coli strains provided meaningful information for B2 APEC/ExPEC-specific virulence factors, including several adhesins, invasins, toxins, iron acquisition systems, and so on. The pathogenicity tests of IMT5155 and other APEC O1:K1 and O2:K1 serotypes strains (isolated in China) through four animal models showed that they were highly virulent for avian colisepticemia and able to cause septicemia and meningitis in neonatal rats, suggesting zoonotic potential of these APEC O1:K1 and O2:K1 isolates. PMID:25397580

Global Genome and Transcriptome Analyses of Magnaporthe oryzae Epidemic Isolate 98-06 Uncover Novel Effectors and Pathogenicity-Related Genes, Revealing Gene Gain and Lose Dynamics in Genome Evolution

PubMed Central

Dong, Yanhan; Li, Ying; Zhao, Miaomiao; Jing, Maofeng; Liu, Xinyu; Liu, Muxing; Guo, Xianxian; Zhang, Xing; Chen, Yue; Liu, Yongfeng; Liu, Yanhong; Ye, Wenwu; Zhang, Haifeng; Wang, Yuanchao; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

2015-01-01

Genome dynamics of pathogenic organisms are driven by pathogen and host co-evolution, in which pathogen genomes are shaped to overcome stresses imposed by hosts with various genetic backgrounds through generation of a variety of isolates. This same principle applies to the rice blast pathogen Magnaporthe oryzae and the rice host; however, genetic variations among different isolates of M. oryzae remain largely unknown, particularly at genome and transcriptome levels. Here, we applied genomic and transcriptomic analytical tools to investigate M. oryzae isolate 98-06 that is the most aggressive in infection of susceptible rice cultivars. A unique 1.4 Mb of genomic sequences was found in isolate 98-06 in comparison to reference strain 70-15. Genome-wide expression profiling revealed the presence of two critical expression patterns of M. oryzae based on 64 known pathogenicity-related (PaR) genes. In addition, 134 candidate effectors with various segregation patterns were identified. Five tested proteins could suppress BAX-mediated programmed cell death in Nicotiana benthamiana leaves. Characterization of isolate-specific effector candidates Iug6 and Iug9 and PaR candidate Iug18 revealed that they have a role in fungal propagation and pathogenicity. Moreover, Iug6 and Iug9 are located exclusively in the biotrophic interfacial complex (BIC) and their overexpression leads to suppression of defense-related gene expression in rice, suggesting that they might participate in biotrophy by inhibiting the SA and ET pathways within the host. Thus, our studies identify novel effector and PaR proteins involved in pathogenicity of the highly aggressive M. oryzae field isolate 98-06, and reveal molecular and genomic dynamics in the evolution of M. oryzae and rice host interactions. PMID:25837042

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

Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus.

PubMed

Lowder, Bethan V; Guinane, Caitriona M; Ben Zakour, Nouri L; Weinert, Lucy A; Conway-Morris, Andrew; Cartwright, Robyn A; Simpson, A John; Rambaut, Andrew; Nübel, Ulrich; Fitzgerald, J Ross

2009-11-17

The impact of globalization on the emergence and spread of pathogens is an important veterinary and public health issue. Staphylococcus aureus is a notorious human pathogen associated with serious nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry, which are a large economic burden on the global broiler chicken industry. Here, we provide evidence that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump that occurred approximately 38 years ago (range, 30 to 63 years ago) by a subtype of the worldwide human ST5 clonal lineage unique to Poland. In contrast to human subtypes of the ST5 radiation, which demonstrate strong geographic clustering, the poultry ST5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. The poultry ST5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. These genetic events have resulted in enhanced resistance to killing by chicken heterophils, reflecting avian host-adaptive evolution. Taken together, we have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens.

Genetic and Pathogenic Variability of Fusarium oxysporum f. sp. cepae Isolated from Onion and Welsh Onion in Japan.

PubMed

Sasaki, Kazunori; Nakahara, Katsuya; Tanaka, Shuhei; Shigyo, Masayoshi; Ito, Shin-ichi

2015-04-01

Fusarium oxysporum f. sp. cepae causes Fusarium basal rot in onion (common onion) and Fusarium wilt in Welsh onion. Although these diseases have been detected in various areas in Japan, knowledge about the genetic and pathogenic variability of F. oxysporum f. sp. cepae is very limited. In this study, F. oxysporum f. sp. cepae was isolated from onion and Welsh onion grown in 12 locations in Japan, and a total of 55 F. oxysporum f. sp. cepae isolates (27 from onion and 28 from Welsh onion) were characterized based on their rDNA intergenic spacer (IGS) and translation elongation factor-1α (EF-1α) nucleotide sequences, vegetative compatibility groups (VCGs), and the presence of the SIX (secreted in xylem) homologs. Phylogenetic analysis of IGS sequences showed that these isolates were grouped into eight clades (A to H), and 20 onion isolates belonging to clade H were monophyletic and assigned to the same VCG. All the IGS-clade H isolates possessed homologs of SIX3, SIX5, and SIX7. The SIX3 homolog was located on a 4 Mb-sized chromosome in the IGS-clade H isolates. Pathogenicity tests using onion seedlings showed that all the isolates with high virulence were in the IGS-clade H. These results suggest that F. oxysporum f. sp. cepae isolates belonging to the IGS-clade H are genetically and pathogenically different from those belonging to the other IGS clades.

[A report of atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum caused by a de novo mutation in tubulin beta 4A (TUBB4A) gene and literature review].

PubMed

Du, Y; Li, C; Guo, J; Guo, P; Li, Z Y; Zhang, W

2017-06-01

Objective: To explore the clinical symptoms and neuroimaging features of a patient with atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (H-ABC) caused by a novel TUBB4A mutation. Methods: We analyzed the clinical data, imaging features and the result of genetic testing of a case diagnosed as atypical H-ABC. Results: The initial symptoms were progressive spasticity, mild cerebellar ataxia and mild cognitive impairment. MRI showed regional blurring of slight high signal on T(2)-weight and FLAIR image in white matter of the bilateral midbrain ventral, internal capsule, posteior horn of lateral ventricle and centrum semiovale, with normal bilateral cerebellar and caudoputamen nucleus. Compared with normal subjects of the same age and gender, hypometabolism was found by (18)F-FDG-PET in brainstem, cerebellar and caudoputamen nucleus in the patient. Genetic testing revealed a de novo pathogenic exome missense heterozygous mutations c. 70G>A in TUBB4A, which was not reported in the human gene mutation database (HGMDpro) and was assessed to be a pathogenic mutation by pathogenic mutation prediction software. Conclusions: The diversity of TUBB4A gene mutations may cause different functional and/or structural impairment in subcortical white matter, cerebellar and caudoputamen nucleus, leading to atypical symptoms and neuroimaging features. Genetic testing for pathogenic mutation in TUBB 4A gene is a key for the diagnosis of H - ABC .

AMPK in Pathogens.

PubMed

Mesquita, Inês; Moreira, Diana; Sampaio-Marques, Belém; Laforge, Mireille; Cordeiro-da-Silva, Anabela; Ludovico, Paula; Estaquier, Jérôme; Silvestre, Ricardo

2016-01-01

During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host-pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.

A Single, Plastic Population of Mycosphaerella pinodes Causes Ascochyta Blight on Winter and Spring Peas (Pisum sativum) in France

PubMed Central

Guibert, Michèle; Leclerc, Aurélie; Andrivon, Didier; Tivoli, Bernard

2012-01-01

Plant diseases are caused by pathogen populations continuously subjected to evolutionary forces (genetic flow, selection, and recombination). Ascochyta blight, caused by Mycosphaerella pinodes, is one of the most damaging necrotrophic pathogens of field peas worldwide. In France, both winter and spring peas are cultivated. Although these crops overlap by about 4 months (March to June), primary Ascochyta blight infections are not synchronous on the two crops. This suggests that the disease could be due to two different M. pinodes populations, specialized on either winter or spring pea. To test this hypothesis, 144 pathogen isolates were collected in the field during the winter and spring growing seasons in Rennes (western France), and all the isolates were genotyped using amplified fragment length polymorphism (AFLP) markers. Furthermore, the pathogenicities of 33 isolates randomly chosen within the collection were tested on four pea genotypes (2 winter and 2 spring types) grown under three climatic regimes, simulating winter, late winter, and spring conditions. M. pinodes isolates from winter and spring peas were genetically polymorphic but not differentiated according to the type of cultivars. Isolates from winter pea were more pathogenic than isolates from spring pea on hosts raised under winter conditions, while isolates from spring pea were more pathogenic than those from winter pea on plants raised under spring conditions. These results show that disease developed on winter and spring peas was initiated by a single population of M. pinodes whose pathogenicity is a plastic trait modulated by the physiological status of the host plant. PMID:23023742

Seteria viridis as a model for pathogen resistance in the Poaceae

USDA-ARS?s Scientific Manuscript database

Seteria viridis is an effective model system for functional genetics in the C4 Poaceae grasses, which include important crops like maize, sorghum, and sugar cane. The small genome size, short stature, rapid life cycle, and the availability of genetic transformation protocols, make Seteria an attract...

Genetic differentiation at microsatellite loci among populations of Mycosphaerella Graminicola from California, Indiana, Kansas and North Dakota

USDA-ARS?s Scientific Manuscript database

Mycosphaerella graminicola causes Septoria tritici blotch and is considered one of the most devastating pathogens of wheat. Although the genetic structures of M. graminicola populations from different countries have been analyzed using various molecular markers, relatively little is known about thos...

A holistic approach to genetic conservation of Pinus strobiformis

Treesearch

K.M. Waring; R. Sniezko; B.A. Goodrich; C. Wehenkel; J.J. Jacobs

2017-01-01

Pinus strobiformis (southwestern white pine) is threatened by both a rapidly changing climate and the tree disease white pine blister rust, caused by an introduced fungal pathogen, Cronartium ribicola. We began a proactive program in ~2009 to sustain P. strobiformis that includes genetic conservation, research, and management strategies. Research...

A Genetic Linkage Map of Mycosphaerella Fijiensis, using SSR and DArT Markers

USDA-ARS?s Scientific Manuscript database

Mycosphaerella fijiensis is the causal agent of black leaf streak or Black Sigatoka disease in bananas. This pathogen threatens global banana production as the main export Cavendish cultivars are highly susceptible. Previously a genetic linkage map was generated predominantly using anonymous AFLP ma...

Inferences on the phylogeography of the fungal pathogen Heterobasidion annosum, including evidence of interspecific horizontal genetic transfer and of human-mediated, long-range dispersal

Treesearch

R.E. Linzer; W.J. Otrosina; P. Gonthier; J. Bruhn; G. Laflamme; G. Bussieres; M. Garbelotto

2008-01-01

Fungi in the basidiomycete species complex Heterobasidion annosum are significant root-rot pathogens of conifers throughout the northern hemisphere. We utilize a multilocus phylogenetic approach to examine hypotheses regarding the evolution and divergence of two Heterobasidion taxa associated with pines: the Eurasian H. ...

Genetic modification of European winegrapes with genes from an American wild relative confers resistance to the major diseases powdery and downy mildew

USDA-ARS?s Scientific Manuscript database

The two most economically important diseases of grapevine cultivation worldwide are caused by the fungal pathogen powdery mildew (Erysiphe necator syn. Uncinula necator) and the oomycete, downy mildew (Plasmopara viticola). These pathogens, endemic to North America, were introduced into Europe in t...

Vibrational spectroscopy-based chemometrics to map host resistance to sudden oak death

Treesearch

Pierluigi (Enrico) Bonello; Anna O. Conrad; Luis Rodriguez Saona; Brice A. McPherson; David L. Wood

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 conservation efforts. This project is predicated on the fact that genetic resistance is the cornerstone for protecting plants against pathogens and insects in environments conducive to the attacking organisms, a...

Population subdivision of Fusarium graminearum from barley and wheat in the upper Midwestern United States at the turn of the century

USDA-ARS?s Scientific Manuscript database

Fusarium graminearum, the causal agent of Fusarium head blight (FHB) in wheat and barley, is one of the most economically destructive pathogens of these grains worldwide. Recent population genetic studies of the pathogen obtained from wheat in North America supported population subdivision in part c...

Spread, genetic variation and methods for the detection of Puccinia kuehnii, the causal agent of sugarcane orange rust.

USDA-ARS?s Scientific Manuscript database

Sugarcane is susceptible to infection by two rust pathogens, Puccinia melanocephala and P. kuehnii, causing brown and orange rust, respectively. Orange rust of sugarcane was first reported in the Western hemisphere in Florida in July 2007. The pathogen was found to be distributed widely throughout t...

Cell wall chitosan is necessary for virulence in the opportunistic pathogen Cryptococcus neoformans.

PubMed

Baker, Lorina G; Specht, Charles A; Lodge, Jennifer K

2011-09-01

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. Its cell wall is composed of glucans, proteins, chitin, and chitosan. Multiple genetic approaches have defined a chitosan-deficient syndrome that includes slow growth and decreased cell integrity. Here we demonstrate chitosan is necessary for virulence and persistence in the mammalian host.

An interspecific barberry hybrid enables genetic dissection of non-host resistance to the wheat stem rust pathogen

USDA-ARS?s Scientific Manuscript database

Stem rust, caused by the macrocyclic fungal pathogen Puccinia graminis (Pg), is one of the most devastating diseases of wheat and other small grains globally; and the emergence of new stem rust races virulent on deployed resistance genes brings urgency to the discovery of more durable sources of gen...

Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy.

PubMed

Holland, Katherine D; Bouley, Thomas M; Horn, Paul S

2017-07-01

Variants in neuronal voltage-gated sodium channel α-subunits genes SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and other autosomal dominant childhood epilepsy syndromes. However, in clinical practice, missense variants are often classified as variants of uncertain significance when missense variants are identified but heritability cannot be determined. Genetic testing reports often include results of computational tests to estimate pathogenicity and the frequency of that variant in population-based databases. The objective of this work was to enhance clinicians' understanding of results by (1) determining how effectively computational algorithms predict epileptogenicity of sodium channel (SCN) missense variants; (2) optimizing their predictive capabilities; and (3) determining if epilepsy-associated SCN variants are present in population-based databases. This will help clinicians better understand the results of indeterminate SCN test results in people with epilepsy. Pathogenic, likely pathogenic, and benign variants in SCNs were identified using databases of sodium channel variants. Benign variants were also identified from population-based databases. Eight algorithms commonly used to predict pathogenicity were compared. In addition, logistic regression was used to determine if a combination of algorithms could better predict pathogenicity. Based on American College of Medical Genetic Criteria, 440 variants were classified as pathogenic or likely pathogenic and 84 were classified as benign or likely benign. Twenty-eight variants previously associated with epilepsy were present in population-based gene databases. The output provided by most computational algorithms had a high sensitivity but low specificity with an accuracy of 0.52-0.77. Accuracy could be improved by adjusting the threshold for pathogenicity. Using this adjustment, the Mendelian Clinically Applicable Pathogenicity (M-CAP) algorithm had an accuracy of 0.90 and a combination of algorithms increased the accuracy to 0.92. Potentially pathogenic variants are present in population-based sources. Most computational algorithms overestimate pathogenicity; however, a weighted combination of several algorithms increased classification accuracy to >0.90. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

DEVELOPMENT AND EVALUATION OF AN INNOVATIVE SYSTEM FOR THE CONCENTRATION AND QUANTITATIVE DETECTION OF CCL PATHOGENS IN DRINKING WATER

EPA Science Inventory

Equipment

The Grafton and Boston Tufts laboratories are impressively equipped to perform this work. They were able to work with the company Haemonetics to make a new automated centrifuge, with remote control and offline capabilities. Sadly, while...

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

PubMed

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

2014-02-01

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

Of woods and webs: possible alternatives to the tree of life for studying genomic fluidity in E. coli.

PubMed

Beauregard-Racine, Julie; Bicep, Cédric; Schliep, Klaus; Lopez, Philippe; Lapointe, François-Joseph; Bapteste, Eric

2011-07-20

We introduce several forest-based and network-based methods for exploring microbial evolution, and apply them to the study of thousands of genes from 30 strains of E. coli. This case study illustrates how additional analyses could offer fast heuristic alternatives to standard tree of life (TOL) approaches. We use gene networks to identify genes with atypical modes of evolution, and genome networks to characterize the evolution of genetic partnerships between E. coli and mobile genetic elements. We develop a novel polychromatic quartet method to capture patterns of recombination within E. coli, to update the clanistic toolkit, and to search for the impact of lateral gene transfer and of pathogenicity on gene evolution in two large forests of trees bearing E. coli. We unravel high rates of lateral gene transfer involving E. coli (about 40% of the trees under study), and show that both core genes and shell genes of E. coli are affected by non-tree-like evolutionary processes. We show that pathogenic lifestyle impacted the structure of 30% of the gene trees, and that pathogenic strains are more likely to transfer genes with one another than with non-pathogenic strains. In addition, we propose five groups of genes as candidate mobile modules of pathogenicity. We also present strong evidence for recent lateral gene transfer between E. coli and mobile genetic elements. Depending on which evolutionary questions biologists want to address (i.e. the identification of modules, genetic partnerships, recombination, lateral gene transfer, or genes with atypical evolutionary modes, etc.), forest-based and network-based methods are preferable to the reconstruction of a single tree, because they provide insights and produce hypotheses about the dynamics of genome evolution, rather than the relative branching order of species and lineages. Such a methodological pluralism - the use of woods and webs - is to be encouraged to analyse the evolutionary processes at play in microbial evolution.This manuscript was reviewed by: Ford Doolittle, Tal Pupko, Richard Burian, James McInerney, Didier Raoult, and Yan Boucher.

Characterization of pathogenic Enterococcus cecorum from different poultry groups: Broiler chickens, layers, turkeys, and waterfowl.

PubMed

Dolka, Beata; Chrobak-Chmiel, Dorota; Czopowicz, Michał; Szeleszczuk, Piotr

2017-01-01

Enterococcus cecorum (EC) is known as a commensal in the intestines of mammals and birds. However, it has been described as an emerging pathogen in poultry industry worldwide. The aim of this study was to analyze and compare EC isolated from clinical material collected from poultry groups with different production purposes. The genetic diversity among pathogenic EC in relation to each specific poultry type was examined. In total, 148 isolates from independent infection outbreaks (2011-2016) were used: 76 broiler chickens (CB), 37 broiler breeders (BB), 23 layers (CL), 7 waterfowl (W) and 5 turkey (T) flocks (1 isolate/1 flock). We provided age ranges at diagnosis of EC-infection for 5 poultry groups. Isolates obtained from CB were significantly more frequently retrieved from bone marrow, joints, spine, and contrary to BB, CL less frequently retrieved from respiratory system. The study showed differences between EC of various poultry types in relation to 10/32 (31.3%) biochemical parameters. EC isolates from CB were significantly more often positive for βGAL, βNAG, MLZ, and less often positive for PAL and βMAN than isolates from other poultry types. However, BB and W isolates showed higher ability to metabolise mannitol than CB, CL, and T. CB isolates showed lower ability to survive at 60°C. Only chicken EC-isolates harbored virulence genes: CB (8.1%) > BB (3.4%) > CL (2%). No specific pulsotype of EC was associated with a specific poultry. One or several various (up to 6) genetic types of EC may be involved in outbreaks in CB flocks within one year in one region. Outbreaks reported in following years in the same region were usually caused by a distinct set of EC-genetic types. PFGE results indicated at the genetic heterogeneity among pathogenic isolates involved in outbreaks in relation to each poultry type. To our best knowledge, this is the first study which provides a comparison between clinical EC from 5 poultry groups. The study provides a new insight into EC as pathogen of different bird species. The obtained data may be useful in further studies on EC-infections more focused on a specific type of poultry.

[Origin of the plague microbe Yersinia pestis: structure of the process of speciation].

PubMed

Suntsov, V V

2012-01-01

The origin and evolution of the plague microbe Yersinia pestis are considered in the context of propositions of modern Darwinism. It was shown that the plague pathogen diverged from the pseudotuberculous microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan: 22000-15000 years ago. Speciation occurred in the tarbagan (Marmota sibirica)--flea (Oropsylla silantiewi) parasitic system. The structure of the speciation process included six stages: isolation, genetic drift, enhancement of intrapopulational polymorphism, the beginning of pesticin synthesis (genetic conflict and emergence of hiatus), specialization (stabilization of characteristics), and adaptive irradiation (transformation of the monotypic species Y. pestis tarbagani into a polytypic species). The scenario opens up wide prospects for construction of the molecular phylogeny of the plague microbe Y. pestis and for investigation of the biochemical and molecular-genetic aspects of "Darwinian" evolution of pathogens from many other nature-focal infections.

Potential applications of cryogenic technologies to plant genetic improvement and pathogen eradication.

PubMed

Wang, Biao; Wang, Ren-Rui; Cui, Zhen-Hua; Bi, Wen-Lu; Li, Jing-Wei; Li, Bai-Quan; Ozudogru, Elif Aylin; Volk, Gayle M; Wang, Qiao-Chun

2014-01-01

Rapid increases in human populations provide a great challenge to ensure that adequate quantities of food are available. Sustainable development of agricultural production by breeding more productive cultivars and by increasing the productive potential of existing cultivars can help meet this demand. The present paper provides information on the potential uses of cryogenic techniques in ensuring food security, including: (1) long-term conservation of a diverse germplasm and successful establishment of cryo-banks; (2) maintenance of the regenerative ability of embryogenic tissues that are frequently the target for genetic transformation; (3) enhancement of genetic transformation and plant regeneration of transformed cells, and safe, long-term conservation for transgenic materials; (4) production and maintenance of viable protoplasts for transformation and somatic hybridization; and (5) efficient production of pathogen-free plants. These roles demonstrate that cryogenic technologies offer opportunities to ensure food security. Copyright © 2014 Elsevier Inc. All rights reserved.

Reverse Genetics for Newcastle Disease Virus as a Vaccine Vector.

PubMed

Kim, Shin-Hee; Samal, Siba K

2018-02-22

Newcastle disease virus (NDV) is an economically important pathogen in the poultry industry worldwide. Recovery of infectious NDV from cDNA using reverse genetics has made it possible to manipulate the genome of NDV. This has greatly contributed to our understanding of the molecular biology and pathogenesis of NDV. Furthermore, NDV has modular genome and accommodates insertion of a foreign gene as a transcriptional unit, thus enabling NDV as a vaccine vector against diseases of humans and animals. Avirulent NDV strains (e.g., LaSota and B1) have been commonly used as vaccine vectors. In this protocol, we have described reverse genetics of NDV to be used as a vaccine vector by exemplifying the recovery of NDV vectored avian influenza virus vaccine. Specifically, cloning and recovery of NDV expressing the hemagglutinin protein of highly pathogenic influenza virus were explained. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Differential divergences of obligately insect-pathogenic Entomophthora species from fly and aphid hosts.

PubMed

Jensen, Annette Bruun; Eilenberg, Jørgen; López Lastra, Claudia

2009-11-01

Three DNA regions (ITS 1, LSU rRNA and GPD) of isolates from the insect-pathogenic fungus genus Entomophthora originating from different fly (Diptera) and aphid (Hemiptera) host taxa were sequenced. The results documented a large genetic diversity among the fly-pathogenic Entomophthora and only minor differences among aphid-pathogenic Entomophthora. The evolutionary time of divergence of the fly and the aphid host taxa included cannot account for this difference. The host-driven divergence of Entomophthora, therefore, has been much greater in flies than in aphids. Host-range differences or a recent host shift to aphid are possible explanations.

Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.

PubMed

Partemi, Sara; Vidal, Monica Coll; Striano, Pasquale; Campuzano, Oscar; Allegue, Catarina; Pezzella, Marianna; Elia, Maurizio; Parisi, Pasquale; Belcastro, Vincenzo; Casellato, Susanna; Giordano, Lucio; Mastrangelo, Massimo; Pietrafusa, Nicola; Striano, Salvatore; Zara, Federico; Bianchi, Amedeo; Buti, Daniela; La Neve, Angela; Tassinari, Carlo Alberto; Oliva, Antonio; Brugada, Ramon

2015-05-01

Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.

Keeping it together: absence of genetic variation and DNA incorporation by the predatory bacteria Micavibrio aeruginosavorus and Bdellovibrio bacteriovorus during predation.

PubMed

Gupta, Shilpi; Lemenze, Alexander; Donnelly, Robert J; Connell, Nancy D; Kadouri, Daniel E

2018-05-08

The use of predatory bacteria as a potential live therapeutic to control human infection is gaining increased attention. Earlier work with Micavibrio spp. and Bdellovibrio spp. has demonstrated the ability of these predators to control drug-resistant Gram-negative pathogens, Tier-1 select agents and biofilms. Additional studies also confirmed that introducing high doses of the predators into animals does not negatively impact animal well-being and might assist in reducing bacterial burden in vivo. The survival of predators requires extreme proximity to the prey cell, which might bring about horizontal transfer of genetic material, such as genes encoding for pathogenic genetic islands that would indirectly facilitate the spread of genetic material to other organisms. In this study, we examined the genetic makeup of several lab isolates of the predators B. bacteriovorus and M. aeruginosavorus that were cultured repeatedly and stored over a course of 13 years. We also conducted controlled experiments in which the predators were sequentially co-cultured on Klebsiella pneumoniae followed by genetic analysis of the predator. In both cases, we saw little genetic variation and no evidence of horizontally transferred chromosomal DNA from the prey during predator-prey interaction. Culturing the predators repeatedly did not cause any change in predation efficacy. Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches.

PubMed

Guidugli, Lucia; Shimelis, Hermela; Masica, David L; Pankratz, Vernon S; Lipton, Gary B; Singh, Namit; Hu, Chunling; Monteiro, Alvaro N A; Lindor, Noralane M; Goldgar, David E; Karchin, Rachel; Iversen, Edwin S; Couch, Fergus J

2018-01-17

Many variants of uncertain significance (VUS) have been identified in BRCA2 through clinical genetic testing. VUS pose a significant clinical challenge because the contribution of these variants to cancer risk has not been determined. We conducted a comprehensive assessment of VUS in the BRCA2 C-terminal DNA binding domain (DBD) by using a validated functional assay of BRCA2 homologous recombination (HR) DNA-repair activity and defined a classifier of variant pathogenicity. Among 139 variants evaluated, 54 had ≥99% probability of pathogenicity, and 73 had ≥95% probability of neutrality. Functional assay results were compared with predictions of variant pathogenicity from the Align-GVGD protein-sequence-based prediction algorithm, which has been used for variant classification. Relative to the HR assay, Align-GVGD significantly (p < 0.05) over-predicted pathogenic variants. We subsequently combined functional and Align-GVGD prediction results in a Bayesian hierarchical model (VarCall) to estimate the overall probability of pathogenicity for each VUS. In addition, to predict the effects of all other BRCA2 DBD variants and to prioritize variants for functional studies, we used the endoPhenotype-Optimized Sequence Ensemble (ePOSE) algorithm to train classifiers for BRCA2 variants by using data from the HR functional assay. Together, the results show that systematic functional assays in combination with in silico predictors of pathogenicity provide robust tools for clinical annotation of BRCA2 VUS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Contrasting epidemic histories reveal pathogen-mediated balancing selection on class II MHC diversity in a wild songbird.

PubMed

Hawley, Dana M; Fleischer, Robert C

2012-01-01

The extent to which pathogens maintain the extraordinary polymorphism at vertebrate Major Histocompatibility Complex (MHC) genes via balancing selection has intrigued evolutionary biologists for over half a century, but direct tests remain challenging. Here we examine whether a well-characterized epidemic of Mycoplasmal conjunctivitis resulted in balancing selection on class II MHC in a wild songbird host, the house finch (Carpodacus mexicanus). First, we confirmed the potential for pathogen-mediated balancing selection by experimentally demonstrating that house finches with intermediate to high multi-locus MHC diversity are more resistant to challenge with Mycoplasma gallisepticum. Second, we documented sequence and diversity-based signatures of pathogen-mediated balancing selection at class II MHC in exposed host populations that were absent in unexposed, control populations across an equivalent time period. Multi-locus MHC diversity significantly increased in exposed host populations following the epidemic despite initial compromised diversity levels from a recent introduction bottleneck in the exposed host range. We did not observe equivalent changes in allelic diversity or heterozygosity across eight neutral microsatellite loci, suggesting that the observations reflect selection rather than neutral demographic processes. Our results indicate that a virulent pathogen can exert sufficient balancing selection on class II MHC to rescue compromised levels of genetic variation for host resistance in a recently bottlenecked population. These results provide evidence for Haldane's long-standing hypothesis that pathogens directly contribute to the maintenance of the tremendous levels of genetic variation detected in natural populations of vertebrates.

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses.

PubMed

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nantawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-02-14

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby canine kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 2(9) HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genes, communities & invasive species: understanding the ecological and evolutionary dynamics of host-pathogen interactions.

PubMed

Burdon, J J; Thrall, P H; Ericson, L

2013-08-01

Reciprocal interactions between hosts and pathogens drive ecological, epidemiological and co-evolutionary trajectories, resulting in complex patterns of diversity at population, species and community levels. Recent results confirm the importance of negative frequency-dependent rather than 'arms-race' processes in the evolution of individual host-pathogen associations. At the community level, complex relationships between species abundance and diversity dampen or alter pathogen impacts. Invasive pathogens challenge these controls reflecting the earliest stages of evolutionary associations (akin to arms-race) where disease effects may be so great that they overwhelm the host's and community's ability to respond. Viewing these different stabilization/destabilization phases as a continuum provides a valuable perspective to assessment of the role of genetics and ecology in the dynamics of both natural and invasive host-pathogen associations. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Prospects for advancing defense to cereal rusts through genetical genomics

PubMed Central

Ballini, Elsa; Lauter, Nick; Wise, Roger

2013-01-01

Rusts are one of the most severe threats to cereal crops because new pathogen races emerge regularly, resulting in infestations that lead to large yield losses. In 1999, a new race of stem rust, Puccinia graminis f. sp. tritici (Pgt TTKSK or Ug99), was discovered in Uganda. Most of the wheat and barley cultivars grown currently worldwide are susceptible to this new race. Pgt TTKSK has already spread northward into Iran and will likely spread eastward throughout the Indian subcontinent in the near future. This scenario is not unique to stem rust; new races of leaf rust (Puccinia triticina) and stripe rust (Puccinia striiformis) have also emerged recently. One strategy for countering the persistent adaptability of these pathogens is to stack complete- and partial-resistance genes, which requires significant breeding efforts in order to reduce deleterious effects of linkage drag. These varied resistance combinations are typically more difficult for the pathogen to defeat, since they would be predicted to apply lower selection pressure. Genetical genomics or expression Quantitative Trait Locus (eQTL) analysis enables the identification of regulatory loci that control the expression of many to hundreds of genes. Integrated deployment of these technologies coupled with efficient phenotyping offers significant potential to elucidate the regulatory nodes in genetic networks that orchestrate host defense responses. The focus of this review will be to present advances in genetical genomic experimental designs and analysis, particularly as they apply to the prospects for discovering partial disease resistance alleles in cereals. PMID:23641250

Genetic characterisation of novel, highly pathogenic avian influenza (HPAI) H5N6 viruses isolated in birds, South Korea, November 2016.

PubMed

Si, Young-Jae; Lee, In Won; Kim, Eun-Ha; Kim, Young-Il; Kwon, Hyeok-Il; Park, Su-Jin; Nguyen, Hiep Dinh; Kim, Se Mi; Kwon, Jin-Jung; Choi, Won-Suk; Beak, Yun Hee; Song, Min-Suk; Kim, Chul-Joong; Webby, Richard J; Choi, Young-Ki

2017-01-05

A novel genotype of H5N6 influenza viruses was isolated from migratory birds in South Korea during November 2016. Domestic outbreaks of this virus were associated with die-offs of wild birds near reported poultry cases in Chungbuk province, central South Korea. Genetic analysis and animal studies demonstrated that the Korean H5N6 viruses are highly pathogenic avian influenza (HPAI) viruses and that these viruses are novel reassortants of at least three different subtypes (H5N6, H4N2 and H1N1). This article is copyright of The Authors, 2017.

Isolates of Cryptococcus neoformans from Infected Animals Reveal Genetic Exchange in Unisexual, α Mating Type Populations▿ †

PubMed Central

Bui, Tien; Lin, Xiaorong; Malik, Richard; Heitman, Joseph; Carter, Dee

2008-01-01

Sexual reproduction and genetic exchange are important for the evolution of fungal pathogens and for producing potentially infective spores. Studies to determine whether sex occurs in the pathogenic yeast Cryptococcus neoformans var. grubii have produced enigmatic results, however: basidiospores are the most likely infective propagules, and clinical isolates are fertile and genetically diverse, consistent with a sexual species, but almost all populations examined consist of a single mating type and have little evidence for genetic recombination. The choice of population is critical when looking for recombination, particularly when significant asexual propagation is likely and when latency may complicate assessing the origin of an isolate. We therefore selected isolates from infected animals living in the region of Sydney, Australia, with the assumption that the relatively short life spans and limited travels of the animal hosts would provide a very defined population. All isolates were mating type α and were of molecular genotype VNI or VNII. A lack of linkage disequilibrium among loci suggested that genetic exchange occurred within both genotype groups. Four diploid VNII isolates that produced filaments and basidium-like structures when cultured in proximity to an a mating type strain were found. Recent studies suggest that compatible α-α unions can occur in C. neoformans var. neoformans populations and in populations of the sibling species Cryptococcus gattii. As a mating type strains of C. neoformans var. grubii have never been found in Australia, or in the VNII molecular type globally, the potential for α-α unions is evidence that α-α unisexual mating maintains sexual recombination and diversity in this pathogen and may produce infectious propagules. PMID:18552280

Homologous genetic recombination in the yellow head complex of nidoviruses infecting Penaeus monodon shrimp.

PubMed

Wijegoonawardane, Priyanjalie K M; Sittidilokratna, Nusra; Petchampai, Natthida; Cowley, Jeff A; Gudkovs, Nicholas; Walker, Peter J

2009-07-20

Yellow head virus (YHV) is a highly virulent pathogen of Penaeus monodon shrimp. It is one of six known genotypes in the yellow head complex of nidoviruses which also includes mildly pathogenic gill-associated virus (GAV, genotype 2) and four other genotypes (genotypes 3-6) that have been detected only in healthy shrimp. In this study, comparative phylogenetic analyses conducted on replicase- (ORF1b) and glycoprotein- (ORF3) gene amplicons identified 10 putative natural recombinants amongst 28 viruses representing all six genotypes from across the Indo-Pacific region. The approximately 4.6 kb genomic region spanning the two amplicons was sequenced for three putative recombinant viruses from Vietnam (genotype 3/5), the Philippines (genotype 5/2) and Indonesia (genotype 3/2). SimPlot analysis using these and representative parental virus sequences confirmed that each was a recombinant genotype and identified a recombination hotspot in a region just upstream of the ORF1b C-terminus. Maximum-likelihood breakpoint analysis predicted identical crossover positions in the Vietnamese and Indonesian recombinants, and a crossover position 12 nt upstream in the Philippine recombinant. Homologous genetic recombination in the same genome region was also demonstrated in recombinants generated experimentally in shrimp co-infected with YHV and GAV. The high frequency with which natural recombinants were identified indicates that genetic exchange amongst genotypes is occurring commonly in Asia and playing a significant role in expanding the genetic diversity in the yellow head complex. This is the first evidence of genetic recombination in viruses infecting crustaceans and has significant implications for the pathogenesis of infection and diagnosis of these newly emerging invertebrate pathogens.

A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity.

PubMed

Gong, Yu-Nong; Chen, Guang-Wu; Yang, Shu-Li; Lee, Ching-Ju; Shih, Shin-Ru; Tsao, Kuo-Chien

2016-01-01

Forty-two cytopathic effect (CPE)-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5-6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS) was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV) in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs), 10 HPeVs, 1 human adenovirus (HAdV), 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.

Characterization of the Active Microbiotas Associated with Honey Bees Reveals Healthier and Broader Communities when Colonies are Genetically Diverse

PubMed Central

Mattila, Heather R.; Rios, Daniela; Walker-Sperling, Victoria E.; Roeselers, Guus; Newton, Irene L. G.

2012-01-01

Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected pollen into bee bread, a nutritious food product that can be stored for long periods in colonies. We used 16S rRNA pyrosequencing to comprehensively characterize in genetically diverse and genetically uniform colonies the active bacterial communities that are found on honey bees, in their digestive tracts, and in bee bread. This method provided insights that have not been revealed by past studies into the content and benefits of honey bee-associated microbial communities. Colony microbiotas differed substantially between sampling environments and were dominated by several anaerobic bacterial genera never before associated with honey bees, but renowned for their use by humans to ferment food. Colonies with genetically diverse populations of workers, a result of the highly promiscuous mating behavior of queens, benefited from greater microbial diversity, reduced pathogen loads, and increased abundance of putatively helpful bacteria, particularly species from the potentially probiotic genus Bifidobacterium. Across all colonies, Bifidobacterium activity was negatively correlated with the activity of genera that include pathogenic microbes; this relationship suggests a possible target for understanding whether microbes provide protective benefits to honey bees. Within-colony diversity shapes microbiotas associated with honey bees in ways that may have important repercussions for colony function and health. Our findings illuminate the importance of honey bee-bacteria symbioses and examine their intersection with nutrition, pathogen load, and genetic diversity, factors that are considered key to understanding honey bee decline. PMID:22427917

Clinical Applications of Molecular Genetic Discoveries

PubMed Central

Marian, A.J.

2015-01-01

Genome-wide association studies (GWAS) of complex traits have mapped more than 15,000 common single nucleotide variants (SNVs). Likewise, applications of massively parallel nucleic acid sequencing technologies often referred to as Next Generation Sequencing, to molecular genetic studies of complex traits have catalogued a large number of rare variants (population frequency of <0.01) in cases with complex traits. Moreover, high throughput nucleic acid sequencing, variant burden analysis, and linkage studies are illuminating the presence of large number of SNVs in cases and families with single gene disorders. The plethora of the genetic variants has exposed the formidable challenge of identifying the causal and pathogenic variants from the enormous number of innocuous common and rare variants that exist in the population as well as in an individual genome. The arduous task of identifying the causal and pathogenic variants is further compounded by the pleiotropic effects of the variants, complexity of cis and trans interactions in the genome, variability in phenotypic expression of the disease, as well as phenotypic plasticity, and the multifarious determinants of the phenotype. Population genetic studies offer the initial roadmaps and have the potential to elucidate novel pathways involved in the pathogenesis of the disease. However, the genome of an individual is unique, rendering unambiguous identification of the causal or pathogenic variant in a single individual exceedingly challenging. Yet, the focus of the practice of medicine is on the individual, as Sir William Osler elegantly expressed in his insightful quotation: “The good physician treats the disease; the great physician treats the patient who has the disease.” The daunting task facing physicians, patients, and researchers alike is to apply the modern genetic discoveries to care of the individual with or at risk of the disease. PMID:26548329

A MLVA Genotyping Scheme for Global Surveillance of the Citrus Pathogen Xanthomonas citri pv. citri Suggests a Worldwide Geographical Expansion of a Single Genetic Lineage

PubMed Central

Boyer, Karine; Leduc, Alice; Tourterel, Christophe; Drevet, Christine; Ravigné, Virginie; Gagnevin, Lionel; Guérin, Fabien; Chiroleu, Frédéric; Koebnik, Ralf; Verdier, Valérie; Vernière, Christian

2014-01-01

MultiLocus Variable number of tandem repeat Analysis (MLVA) has been extensively used to examine epidemiological and evolutionary issues on monomorphic human pathogenic bacteria, but not on bacterial plant pathogens of agricultural importance albeit such tools would improve our understanding of their epidemiology, as well as of the history of epidemics on a global scale. Xanthomonas citri pv. citri is a quarantine organism in several countries and a major threat for the citrus industry worldwide. We screened the genomes of Xanthomonas citri pv. citri strain IAPAR 306 and of phylogenetically related xanthomonads for tandem repeats. From these in silico data, an optimized MLVA scheme was developed to assess the global diversity of this monomorphic bacterium. Thirty-one minisatellite loci (MLVA-31) were selected to assess the genetic structure of 129 strains representative of the worldwide pathological and genetic diversity of X. citri pv. citri. Based on Discriminant Analysis of Principal Components (DAPC), four pathotype-specific clusters were defined. DAPC cluster 1 comprised strains that were implicated in the major geographical expansion of X. citri pv. citri during the 20th century. A subset of 12 loci (MLVA-12) resolved 89% of the total diversity and matched the genetic structure revealed by MLVA-31. MLVA-12 is proposed for routine epidemiological identification of X. citri pv. citri, whereas MLVA-31 is proposed for phylogenetic and population genetics studies. MLVA-31 represents an opportunity for international X. citri pv. citri genotyping and data sharing. The MLVA-31 data generated in this study was deposited in the Xanthomonas citri genotyping database (http://www.biopred.net/MLVA/). PMID:24897119

Statistical Physics of T-Cell Development and Pathogen Specificity

NASA Astrophysics Data System (ADS)

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

2013-04-01

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

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

PubMed Central

Hörger, Anja C.; Ilyas, Muhammad; Stephan, Wolfgang; Tellier, Aurélien; van der Hoorn, Renier A. L.; Rose, Laura E.

2012-01-01

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant–pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the “Guard-Hypothesis,” R proteins (the “guards”) can sense modification of target molecules in the host (the “guardees”) by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the “guardee-effector” interface for pathogen recognition, natural selection acts on the “guard-guardee” interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen. PMID:22829777

Characteristics of two highly pathogenic avian influenza H5N8 viruses with different pathogenicity in mice.

PubMed

Wang, Xiao; Meng, Feifei; Wang, Dandan; Liu, Xing; Chen, Sujuan; Qin, Tao; Peng, Daxin; Liu, Xiufan

2016-12-01

Novel reassortant influenza A (H5N8) viruses are becoming a potential threat not only to the poultry industry but also to public health. Many molecular markers for pathogenicity in mammalian hosts have been identified in other H5 subtype avian influenza viruses (AIVs). However, the pathogenicity of H5N8 AIVs to mammals remains unclear. It is believed that selection of a pair of isolates with a similar genetic background but with different virulence to mammals is a prerequisite for studying the pathogenic mechanism of AIVs. Two avian-origin H5N8 isolates, A/goose/Eastern China/CZ/2013 (CZ13) and A/duck/ Eastern China /JY/2014 (JY14), which shared a similar genetic background (H5 clade 2.3.4.4) and amino acid substitutions that were shown previously to be molecular markers of pathogenicity, were used to determine their biological characteristics and pathogenicity. Hemagglutination assays using α-2,3-sialidase-treated goose red blood cells demonstrated that both viruses exhibited a dual-receptor-binding preference. Viral growth kinetics in vitro indicated that both viruses replicated to high titers in CEF cells (about 10 8.0 TCID 50 /mL). In MDCK cells, however, CZ13 replicated efficiently (10 7.0 TCID 50 /mL), while JY14 grew to peak titers below 10 4.0 TCID 50 /mL. Animal studies indicated that although both viruses were highly virulent in chickens, they exhibited significantly different virulence in mice. CZ13 was highly pathogenic (MLD 50 = 10 1.6 EID 50 ), whereas JY14 had low virulence (MLD 50  > 10 6.5 EID 50 ). Therefore, this pair of viruses can be used to search for unknown molecular markers of virulence and to investigate specific pathogenic mechanisms in mice.

The Relationship between Host Lifespan and Pathogen Reservoir Potential: An Analysis in the System Arabidopsis thaliana-Cucumber mosaic virus

PubMed Central

Hily, Jean Michel; García, Adrián; Moreno, Arancha; Plaza, María; Wilkinson, Mark D.; Fereres, Alberto; Fraile, Aurora; García-Arenal, Fernando

2014-01-01

Identification of the determinants of pathogen reservoir potential is central to understand disease emergence. It has been proposed that host lifespan is one such determinant: short-lived hosts will invest less in costly defenses against pathogens, so that they will be more susceptible to infection, more competent as sources of infection and/or will sustain larger vector populations, thus being effective reservoirs for the infection of long-lived hosts. This hypothesis is sustained by analyses of different hosts of multihost pathogens, but not of different genotypes of the same host species. Here we examined this hypothesis by comparing two genotypes of the plant Arabidopsis thaliana that differ largely both in life-span and in tolerance to its natural pathogen Cucumber mosaic virus (CMV). Experiments with the aphid vector Myzus persicae showed that both genotypes were similarly competent as sources for virus transmission, but the short-lived genotype was more susceptible to infection and was able to sustain larger vector populations. To explore how differences in defense against CMV and its vector relate to reservoir potential, we developed a model that was run for a set of experimentally-determined parameters, and for a realistic range of host plant and vector population densities. Model simulations showed that the less efficient defenses of the short-lived genotype resulted in higher reservoir potential, which in heterogeneous host populations may be balanced by the longer infectious period of the long-lived genotype. This balance was modulated by the demography of both host and vector populations, and by the genetic composition of the host population. Thus, within-species genetic diversity for lifespan and defenses against pathogens will result in polymorphisms for pathogen reservoir potential, which will condition within-population infection dynamics. These results are relevant for a better understanding of host-pathogen co-evolution, and of the dynamics of pathogen emergence. PMID:25375140

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.

Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment.

PubMed

Wu, Ying; McDade, Thomas W; Kuzawa, Christopher W; Borja, Judith; Li, Yun; Adair, Linda S; Mohlke, Karen L; Lange, Leslie A

2012-04-01

Recent genome-wide association studies have related several genetic loci, including C-reactive protein (CRP), hepatocyte nuclear factor 1 homeobox (HNF1A), and genetic variations in the leptin receptor (LEPR), to circulating CRP levels in populations of European ancestry. The genetic effects in other populations and across varying levels of exposure to a pathogenic environment, an important environmental factor associated with CRP, remain to be determined. We tested 2,073,674 single-nucleotide polymorphisms (SNPs) for association with plasma CRP (limited to ≤10 mg/L) in 1,709 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey. The strongest evidence of association was observed with variants at CRP (rs876537, P = 1.4 × 10(-9)) and HNF1A (rs7305618, P = 1.0 × 10(-8)). Among other previously reported CRP-associated loci, the apolipoprotein E ε4 haplotype was associated with decreased CRP level (P = 7.1 × 10(-4)), and modest association was observed with LEPR (rs1892534, P = 0.076), with direction of effects consistent with previous studies. The strongest signal at a locus not previously reported mapped to a gene desert region on chromosome 6q16.1 (rs1408282, P = 2.9 × 10(-6)). Finally, we observed nominal evidence of interaction with exposure to a pathogenic environment for top main effect SNPs at HNF1A (rs7305618, P = 0.031), LEPR (rs1892535, P = 0.030) and 6q16.1 (rs1408282, P = 0.046). Our findings demonstrate convincing evidence that genetic variants in CRP and HNF1A contribute to plasma CRP in Filipino women and provide the first evidence that exposure to a pathogenic environment may modify the genetic influence at the HNF1A, LEPR, and 6q16.1 loci on plasma CRP level.

Microevolution due to pollution in amphibians: A review on the genetic erosion hypothesis.

PubMed

Fasola, E; Ribeiro, R; Lopes, I

2015-09-01

The loss of genetic diversity, due to exposure to chemical contamination (genetic erosion), is a major threat to population viability. Genetic erosion is the loss of genetic variation: the loss of alleles determining the value of a specific trait or set of traits. Almost a third of the known amphibian species is considered to be endangered and a decrease of genetic variability can push them to the verge of extinction. This review indicates that loss of genetic variation due to chemical contamination has effects on: 1) fitness, 2) environmental plasticity, 3) co-tolerance mechanisms, 4) trade-off mechanisms, and 5) tolerance to pathogens in amphibian populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reoccurrence of H5Nx clade 2.3.4.4 highly pathogenic avian influenza viruses in wild birds during 2016

USDA-ARS?s Scientific Manuscript database

The Asian-origin H5N1 A/goose/Guangdong/1/1996 (Gs/GD) lineage of high pathogenicity avian influenza viruses (HPAIV) has become widespread across four continents, affecting poultry, wild birds and humans. H5N1 HPAIV has evolved into multiple hemagglutinin (HA) genetic clades and reassorting with dif...

Transformation of Sclerotinia Sclerotiorum with the Green Fluorescent Protein Gene and Fluorescence of Hyphae in Four Inoculated Hosts

USDA-ARS?s Scientific Manuscript database

Sclerotinia sclerotiorum is an important pathogen of a wide variety of crops. To obtain a genetic marker to observe and study the interaction of the pathogen with its hosts, isolates ND30 and ND21 were transformed using pCT74 and gGFP constructs both containing genes for the green fluorescent protei...

Genetic epidemiology of the Sudden Oak Death pathogen Phytophthora ramorum in California

Treesearch

S. Mascheretti; P.J.P. Croucher; M. Kozanitas; L. Baker; M. Garbelotto

2009-01-01

A total of 669 isolates of Phytophthora ramorum, the pathogen responsible for Sudden Oak Death, were collected from 34 Californian forests and from the ornamental plant-trade. Seven microsatellite markers revealed 82 multilocus genotypes (MGs) of which only three were abundant (>10%). Iteratively collapsing based upon minimum ΦST, yielded five meta-samples and five...

Cell Wall Chitosan Is Necessary for Virulence in the Opportunistic Pathogen Cryptococcus neoformans ▿

PubMed Central

Baker, Lorina G.; Specht, Charles A.; Lodge, Jennifer K.

2011-01-01

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. Its cell wall is composed of glucans, proteins, chitin, and chitosan. Multiple genetic approaches have defined a chitosan-deficient syndrome that includes slow growth and decreased cell integrity. Here we demonstrate chitosan is necessary for virulence and persistence in the mammalian host. PMID:21784998

Superinfection exclusion of the ruminant pathogen anaplasma marginale in the tick vector is dependent on time between exposures to the strains

USDA-ARS?s Scientific Manuscript database

The remarkable genetic diversity of vector-borne pathogens allows for the establishment of superinfection in the mammalian host. To have a long-term impact on population strain structure, the introduced strains must also be transmitted by a vector population that has been exposed to the existing pri...

Towards pathogenomics: a web-based resource for pathogenicity islands

PubMed Central

Yoon, Sung Ho; Park, Young-Kyu; Lee, Soohyun; Choi, Doil; Oh, Tae Kwang; Hur, Cheol-Goo; Kim, Jihyun F.

2007-01-01

Pathogenicity islands (PAIs) are genetic elements whose products are essential to the process of disease development. They have been horizontally (laterally) transferred from other microbes and are important in evolution of pathogenesis. In this study, a comprehensive database and search engines specialized for PAIs were established. The pathogenicity island database (PAIDB) is a comprehensive relational database of all the reported PAIs and potential PAI regions which were predicted by a method that combines feature-based analysis and similarity-based analysis. Also, using the PAI Finder search application, a multi-sequence query can be analyzed onsite for the presence of potential PAIs. As of April 2006, PAIDB contains 112 types of PAIs and 889 GenBank accessions containing either partial or all PAI loci previously reported in the literature, which are present in 497 strains of pathogenic bacteria. The database also offers 310 candidate PAIs predicted from 118 sequenced prokaryotic genomes. With the increasing number of prokaryotic genomes without functional inference and sequenced genetic regions of suspected involvement in diseases, this web-based, user-friendly resource has the potential to be of significant use in pathogenomics. PAIDB is freely accessible at . PMID:17090594

Evidence for the role of synchronicity between host phenology and pathogen activity in the distribution of sudden oak death canker disease.

PubMed

Dodd, Richard S; Hüberli, Daniel; Mayer, Wasima; Harnik, Tamar Y; Afzal-Rafli, Zara; Garbelotto, Matteo

2008-07-01

Variations in synchronicity between colonization rate by the pathogen and host phenology may account for unexplained spatial distribution of canker disease. The hypothesis that synchronous pathogenicity and host development are necessary for incidence of sudden oak death disease was tested by correlating seasonal variations in host cambial phenology and response to inoculation with Phytophthora ramorum. Response to infection was estimated by inoculating branch cuttings from coast live oak (Quercus agrifolia) trees at nine dates through a full annual cycle in 2003-2004. Host phenology was estimated from measurements of bud burst and cambial activity in spring 2006. Lesions were largest in the spring soon after the cambium resumed activity. A moderate genetic component to lesion size was detected. Variation among trees in date of largest lesions correlated with variation in timing of bud burst and cambial phenology. The data support the hypothesis that active host cambial tissue is a necessary requisite for successful infection with the pathogen that causes sudden oak death canker disease. Genetic variation in host phenology will buffer coast live oak against epidemics of this disease.

The human gut resistome.

PubMed

van Schaik, Willem

2015-06-05

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota ('the gut resistome'). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.

A lesson from a reported pathogenic variant in Peutz-Jeghers syndrome: a case report.

PubMed

Tan, Hu; Wei, Xianda; Yang, Pu; Huang, Yanru; Li, Haoxian; Liang, Desheng; Wu, Lingqian

2017-07-01

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by mucocutaneous hyperpigmentation, gastrointestinal (GI) hamartmatous polyps, and an increased risk of various malignancies. Pathogenic variants in the LKB1 tumor suppressor gene (also known as STK11) are the major cause of PJS. In this study, compound heterozygous variants of LKB1, c.890G > A/ c.1062C > G and del(exon1)/ c.1062C > G, were identified in two sporadic Chinese PJS cases respectively. Although all these three variants had been related to the autosomal dominant PJS in previous studies, all evidences collected in this study including de novo data, segregation data, population data, in-silico data, and functional data indicated that del(exon1) and c.890G > A are pathogenic in these two PJS families rather than c.1062C > G. This finding would contribute to genetic counseling for individuals carrying the variant c.1062C > G with or without PJS phenotypes. Moreover, this finding reminds genetic counselors that it is necessary to reevaluate the pathogenicity of reported variants in a known Mendelian disorder in order to avoid a misleading decision.

The human gut resistome

PubMed Central

van Schaik, Willem

2015-01-01

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium. PMID:25918444

Screening and rapid identification of Campylobacter spp. DNA by FlaA PCR based method on chicken and human fecal samples in Egypt

USDA-ARS?s Scientific Manuscript database

Campylobacter is a foodborne pathogen which has a potential public health concern worldwide. Due to discriminatory problems encountered by conventional isolation of Campylobacter spp. and its genetic similarities, rapid molecular techniques for its genetic characterization are useful. In this study,...

Virulence structure of Blumeria graminis f.sp. tritici and its genetic diversity by ISSR and SRAP profiling analyses

USDA-ARS?s Scientific Manuscript database

Blumeria graminis f. sp. tritici is an obligate biotrophic pathogen causing wheat powdery mildew that has a great genetic flexibility and variations in relationship to its host plant. Application of disease resistant cultivars is an essential disease management measurement. Due to its rapid adaptati...

Classification, genetic variation and pathogenicity of Lymantria dispar nucleopolyhedrovirus isolates from Asia, Europe, and North America

USDA-ARS?s Scientific Manuscript database

Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) has been formulated and applied to control outbreaks of the gypsy moth, L. dispar. To classify and determine the degree of genetic variation among isolates of L. dispar NPVs from different parts of the range of the gypsy moth, partial sequence...

QTL meta-analysis provides a comprehensive view of loci controlling partial resistance to Aphanomyces euteiches in four sources of resistance in pea

USDA-ARS?s Scientific Manuscript database

More knowledge about diversity of Quantitative Trait Loci (QTL) controlling polygenic disease resistance in natural genetic variation of crop species is required for durably improving plant genetic resistances to pathogens. Polygenic partial resistance to Aphanomyces root rot, due to Aphanomcyces eu...

New Toxoplasma gondii genotypes isolated from free-range chickens from the Fernando de Noronha, Brazil: unexpected findings

USDA-ARS?s Scientific Manuscript database

Worldwide comparison of Toxoplasma gondii isolates from free range chickens has indicated that T. gondii isolates from Brazil are phenotypically and genetically different than isolates from other countries; most strains from Brazil are pathogenic to mice, there is great genetic variability, most iso...

Genetic diversity, virulence, and Meloidogyne incognita interactions of Fusarium oxysporum isolates causing cotton wilt in Georgia

USDA-ARS?s Scientific Manuscript database

Locally severe outbreaks of Fusarium wilt of cotton (Gossypium spp.) in South Georgia raised concerns about the genotypes of the causal pathogen, Fusarium oxysporum f. sp. vasinfectum. Vegetative complementation tests and DNA sequence analysis were used to determine genetic diversity among 492 F. ox...

Genetic testing and counseling of a recipient after bone marrow transplant from a sibling harboring a germline BRCA1 pathogenic mutation.

PubMed

Škerl, Petra; Krajc, Mateja; Blatnik, Ana; Novaković, Srdjan

2017-07-01

Allogenic bone marrow transplant recipients represent a unique challenge, when they are referred for genetic testing and counseling. When performing genetic testing, it is extremely important to ensure that the detected DNA mutations originate from the patients own DNA, and therefore the most appropriate and reliable biological sample for DNA isolation must be obtained. The aim of the present study was to present the germline testing and counseling approach utilized in a rare case of a chimeric woman who received an allogenic bone marrow transplant from a sibling with a germline BRCA1 pathogenic mutation. According to our results, hairs with follicles are a reliable and ready source of DNA in a patient whose blood is of allogenic bone marrow transplant donor origin. Compared with a fibroblast culture, which is more difficult to obtain, the hair follicles are much more accessible and hair sampling is less invasive for the patient. Genetic testing based on the other sources of DNA, such as buccal swabs, is questionable due to the known risk of donor DNA contamination.

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

Characterization of Pseudomonas syringae pv. syringae, Causal Agent of Citrus Blast of Mandarin in Montenegro.

PubMed

Ivanović, Žarko; Perović, Tatjana; Popović, Tatjana; Blagojević, Jovana; Trkulja, Nenad; Hrnčić, Snježana

2017-02-01

Citrus blast caused by bacterium Pseudomonas syringae is a very important disease of citrus occuring in many areas of the world, but with few data about genetic structure of the pathogen involved. Considering the above fact, this study reports genetic characterization of 43 P. syringae isolates obtained from plant tissue displaying citrus blast symptoms on mandarin ( Citrus reticulata ) in Montenegro, using multilocus sequence analysis of gyrB , rpoD , and gap1 gene sequences. Gene sequences from a collection of 54 reference pathotype strains of P. syringae from the Plant Associated and Environmental Microbes Database (PAMDB) was used to establish a genetic relationship with our isolates obtained from mandarin. Phylogenetic analyses of gyrB , rpoD , and gap1 gene sequences showed that P. syringae pv. syringae causes citrus blast in mandarin in Montenegro, and belongs to genomospecies 1. Genetic homogeneity of isolates suggested that the Montenegrian population might be clonal which indicates a possible common source of infection. These findings may assist in further epidemiological studies of this pathogen and for determining mandarin breeding strategies for P. syringae control.

Characterization of Pseudomonas syringae pv. syringae, Causal Agent of Citrus Blast of Mandarin in Montenegro

PubMed Central

Ivanović, Žarko; Perović, Tatjana; Popović, Tatjana; Blagojević, Jovana; Trkulja, Nenad; Hrnčić, Snježana

2017-01-01

Citrus blast caused by bacterium Pseudomonas syringae is a very important disease of citrus occuring in many areas of the world, but with few data about genetic structure of the pathogen involved. Considering the above fact, this study reports genetic characterization of 43 P. syringae isolates obtained from plant tissue displaying citrus blast symptoms on mandarin (Citrus reticulata) in Montenegro, using multilocus sequence analysis of gyrB, rpoD, and gap1 gene sequences. Gene sequences from a collection of 54 reference pathotype strains of P. syringae from the Plant Associated and Environmental Microbes Database (PAMDB) was used to establish a genetic relationship with our isolates obtained from mandarin. Phylogenetic analyses of gyrB, rpoD, and gap1 gene sequences showed that P. syringae pv. syringae causes citrus blast in mandarin in Montenegro, and belongs to genomospecies 1. Genetic homogeneity of isolates suggested that the Montenegrian population might be clonal which indicates a possible common source of infection. These findings may assist in further epidemiological studies of this pathogen and for determining mandarin breeding strategies for P. syringae control. PMID:28167885

Multigenic Natural Variation Underlies Caenorhabditis elegans Olfactory Preference for the Bacterial Pathogen Serratia marcescens

PubMed Central

Glater, Elizabeth E.; Rockman, Matthew V.; Bargmann, Cornelia I.

2013-01-01

The nematode Caenorhabditis elegans can use olfaction to discriminate among different kinds of bacteria, its major food source. We asked how natural genetic variation contributes to choice behavior, focusing on differences in olfactory preference behavior between two wild-type C. elegans strains. The laboratory strain N2 strongly prefers the odor of Serratia marcescens, a soil bacterium that is pathogenic to C. elegans, to the odor of Escherichia coli, a commonly used laboratory food source. The divergent Hawaiian strain CB4856 has a weaker attraction to Serratia than the N2 strain, and this behavioral difference has a complex genetic basis. At least three quantitative trait loci (QTLs) from the CB4856 Hawaii strain (HW) with large effect sizes lead to reduced Serratia preference when introgressed into an N2 genetic background. These loci interact and have epistatic interactions with at least two antagonistic QTLs from HW that increase Serratia preference. The complex genetic architecture of this C. elegans trait is reminiscent of the architecture of mammalian metabolic and behavioral traits. PMID:24347628

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

PubMed

Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

2017-02-10

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

Genetic Attributes of E. coli Isolates from Chlorinated Drinking Water

PubMed Central

Blyton, Michaela D. J.; Gordon, David M.

2017-01-01

Escherichia coli, is intimately associated with both human health and water sanitation. E. coli isolates from water can either be (i) host associated commensals, indicating recent faecal contamination; (ii) diarrheal pathogens or (iii) extra-intestinal pathogens that pose a direct health risk; or (iv) free-living. In this study we genetically characterised 28 E. coli isolates obtained from treated drinking water in south eastern Australia to ascertain their likely source. We used full genome sequencing to assign the isolates to their phylogenetic group and multi-locus sequence type. The isolates were also screened in silico for several virulence genes and genes involved in acquired antibiotic resistance. The genetic characteristics of the isolates indicated that four isolates were likely human pathogens. However, these isolates were not detected in sufficient numbers to present a health risk to the public. An additional isolate was a human associated strain. Nine isolates were water associated free-living strains that were unlikely to pose a health risk. Only 14% of the isolates belonged to the host associated phylogenetic group (B2) and only a single isolate had any antibiotic resistance genes. This suggests that the primary source of the drinking water E. coli isolates may not have been recent human faecal contamination. PMID:28107364

Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.

PubMed

Fratta, Pietro; Polke, James M; Newcombe, Jia; Mizielinska, Sarah; Lashley, Tammaryn; Poulter, Mark; Beck, Jon; Preza, Elisavet; Devoy, Anny; Sidle, Katie; Howard, Robin; Malaspina, Andrea; Orrell, Richard W; Clarke, Jan; Lu, Ching-Hua; Mok, Kin; Collins, Toby; Shoaii, Maryam; Nanji, Tina; Wray, Selina; Adamson, Gary; Pittman, Alan; Renton, Alan E; Traynor, Bryan J; Sweeney, Mary G; Revesz, Tamas; Houlden, Henry; Mead, Simon; Isaacs, Adrian M; Fisher, Elizabeth M C

2015-01-01

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0-30 hexanucleotide repeats are present in the general population, expansions >500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50-200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic diversity of the human pathogen Vibrio vulnificus: a new phylogroup.

PubMed

Broza, Yoav Y; Raz, Nili; Lerner, Larisa; Danin-Poleg, Yael; Kashi, Yechezkel

2012-02-15

The biotype 3 group of the human pathogen Vibrio vulnificus emerged in Israel probably as a result of genome hybridization of two bacterial populations. We performed a genomic and phylogenetic study of V. vulnificus strains isolated from the environmental niche from which this group emerged - fish aquaculture in Israel. The genetic relationships and evolutionary aspects of 188 environmental and clinical isolates of the bacterium were studied by genomic typing. Genetic relations were determined based on variation at 12 variable number tandem repeat (VNTR, also termed SSR) loci. Analysis revealed a new cluster, in addition to the main groups of biotype 1& 2 and biotype 3. Similar grouping results were obtained with three different statistical approaches. Isolates forming this new cluster presented unclear biochemical profile nevertheless were not identified as biotype 1 or biotype 3. Further examination of representative strains by multilocus sequence typing (MLST) of 10 housekeeping genes and 5 conserved hypothetical genes supported the identification of this as yet undiscovered phylogroup (phenotypically diverse), termed clade A herein. This new clonal subgroup includes environmental as well as clinical isolates. The results highlight the fish aquaculture environment, and possibly man-made ecological niches as a whole, as a source for the emergence of new pathogenic strains. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic Attributes of E. coli Isolates from Chlorinated Drinking Water.

PubMed

Blyton, Michaela D J; Gordon, David M

2017-01-01

Escherichia coli, is intimately associated with both human health and water sanitation. E. coli isolates from water can either be (i) host associated commensals, indicating recent faecal contamination; (ii) diarrheal pathogens or (iii) extra-intestinal pathogens that pose a direct health risk; or (iv) free-living. In this study we genetically characterised 28 E. coli isolates obtained from treated drinking water in south eastern Australia to ascertain their likely source. We used full genome sequencing to assign the isolates to their phylogenetic group and multi-locus sequence type. The isolates were also screened in silico for several virulence genes and genes involved in acquired antibiotic resistance. The genetic characteristics of the isolates indicated that four isolates were likely human pathogens. However, these isolates were not detected in sufficient numbers to present a health risk to the public. An additional isolate was a human associated strain. Nine isolates were water associated free-living strains that were unlikely to pose a health risk. Only 14% of the isolates belonged to the host associated phylogenetic group (B2) and only a single isolate had any antibiotic resistance genes. This suggests that the primary source of the drinking water E. coli isolates may not have been recent human faecal contamination.

Variant Interpretation: Functional Assays to the Rescue.

PubMed

Starita, Lea M; Ahituv, Nadav; Dunham, Maitreya J; Kitzman, Jacob O; Roth, Frederick P; Seelig, Georg; Shendure, Jay; Fowler, Douglas M

2017-09-07

Classical genetic approaches for interpreting variants, such as case-control or co-segregation studies, require finding many individuals with each variant. Because the overwhelming majority of variants are present in only a few living humans, this strategy has clear limits. Fully realizing the clinical potential of genetics requires that we accurately infer pathogenicity even for rare or private variation. Many computational approaches to predicting variant effects have been developed, but they can identify only a small fraction of pathogenic variants with the high confidence that is required in the clinic. Experimentally measuring a variant's functional consequences can provide clearer guidance, but individual assays performed only after the discovery of the variant are both time and resource intensive. Here, we discuss how multiplex assays of variant effect (MAVEs) can be used to measure the functional consequences of all possible variants in disease-relevant loci for a variety of molecular and cellular phenotypes. The resulting large-scale functional data can be combined with machine learning and clinical knowledge for the development of "lookup tables" of accurate pathogenicity predictions. A coordinated effort to produce, analyze, and disseminate large-scale functional data generated by multiplex assays could be essential to addressing the variant-interpretation crisis. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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.

Disease detection in sugar beet fields: a multi-temporal and multi-sensoral approach on different scales

NASA Astrophysics Data System (ADS)

Mahlein, Anne-Katrin; Hillnhütter, Christian; Mewes, Thorsten; Scholz, Christine; Steiner, Ulrike; Dehne, Heinz-Willhelm; Oerke, Erich-Christian

2009-09-01

Depending on environmental factors fungal diseases of crops are often distributed heterogeneously in fields. Precision agriculture in plant protection implies a targeted fungicide application adjusted these field heterogeneities. Therefore an understanding of the spatial and temporal occurrence of pathogens is elementary. As shown in previous studies, remote sensing techniques can be used to detect and observe spectral anomalies in the field. In 2008, a sugar beet field site was observed at different growth stages of the crop using different remote sensing techniques. The experimental field site consisted of two treatments. One plot was sprayed with a fungicide to avoid fungal infections. In order to obtain sugar beet plants infected with foliar diseases the other plot was not sprayed. Remote sensing data were acquired from the high-resolution airborne hyperspectral imaging ROSIS in July 2008 at sugar beet growth stage 39 and from the HyMap sensor systems in August 2008 at sugar beet growth stage 45, respectively. Additionally hyperspectral signatures of diseased and non-diseased sugar beet plants were measured with a non-imaging hand held spectroradiometer at growth stage 49 in September. Ground truth data, in particular disease severity were collected at 50 sampling points in the field. Changes of reflection rates were related to disease severity increasing with time. Erysiphe betae causing powdery mildew was the most frequent leaf pathogen. A classification of healthy and diseased sugar beets in the field was possible by using hyperspectral vegetation indices calculated from canopy reflectance.

Advancing vector biology research: a community survey for future directions, research applications and infrastructure requirements

PubMed Central

Kohl, Alain; Pondeville, Emilie; Schnettler, Esther; Crisanti, Andrea; Supparo, Clelia; Christophides, George K.; Kersey, Paul J.; Maslen, Gareth L.; Takken, Willem; Koenraadt, Constantianus J. M.; Oliva, Clelia F.; Busquets, Núria; Abad, F. Xavier; Failloux, Anna-Bella; Levashina, Elena A.; Wilson, Anthony J.; Veronesi, Eva; Pichard, Maëlle; Arnaud Marsh, Sarah; Simard, Frédéric; Vernick, Kenneth D.

2016-01-01

Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector–pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations. PMID:27677378

Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma.

PubMed

Deml, Brett; Reis, Linda M; Lemyre, Emmanuelle; Clark, Robin D; Kariminejad, Ariana; Semina, Elena V

2016-04-01

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions.

Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma

PubMed Central

Deml, Brett; Reis, Linda M; Lemyre, Emmanuelle; Clark, Robin D; Kariminejad, Ariana; Semina, Elena V

2016-01-01

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions. PMID:26130484

Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome.

PubMed

Tizioto, Polyana C; Kim, JaeWoo; Seabury, Christopher M; Schnabel, Robert D; Gershwin, Laurel J; Van Eenennaam, Alison L; Toaff-Rosenstein, Rachel; Neibergs, Holly L; Taylor, Jeremy F

2015-01-01

Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

Comparative Genomics of Erwinia amylovora and Related Erwinia Species—What do We Learn?

PubMed Central

Zhao, Youfu; Qi, Mingsheng

2011-01-01

Erwinia amylovora, the causal agent of fire blight disease of apples and pears, is one of the most important plant bacterial pathogens with worldwide economic significance. Recent reports on the complete or draft genome sequences of four species in the genus Erwinia, including E. amylovora, E. pyrifoliae, E. tasmaniensis, and E. billingiae, have provided us near complete genetic information about this pathogen and its closely-related species. This review describes in silico subtractive hybridization-based comparative genomic analyses of eight genomes currently available, and highlights what we have learned from these comparative analyses, as well as genetic and functional genomic studies. Sequence analyses reinforce the assumption that E. amylovora is a relatively homogeneous species and support the current classification scheme of E. amylovora and its related species. The potential evolutionary origin of these Erwinia species is also proposed. The current understanding of the pathogen, its virulence mechanism and host specificity from genome sequencing data is summarized. Future research directions are also suggested. PMID:24710213

Integrated oxide graphene based device for laser inactivation of pathogenic microorganisms

NASA Astrophysics Data System (ADS)

Grishkanich, Alexsandr; Ruzankina, Julia; Afanasyev, Mikhail; Paklinov, Nikita; Hafizov, Nail

2018-02-01

We develop device for virus disinfection of pathogenic microorganisms. Viral decontamination can be carried out due to hard ultraviolet irradiation and singlet oxygen destroying the genetic material of a virus capsid. UV rays can destroy DNA, leading to the formation of dimers of nucleic acids. This practically does not occur in tissues, tk. UV rays penetrate badly through them, however, the viral particles are small and UV can destroy their genetic material, RNA / DNA and the virus can not replicate. It is with the construction of the ultraviolet laser water disinfection system (UFLOV) based on the continuous and periodic pulsed ultraviolet laser sources (pump) binds to solve sterility and depyrogenation of water. It has been established that small doses of UV irradiation stimulate reproduction, and large doses cause the death of pathogenic microorganisms. The effect of a dose of ultraviolet is the result of photochemical action on the substance of a living bacterial cell or virion. Also complex photodynamic laser inactivation on graphene oxide is realized.

A complete toolset for the study of Ustilago bromivora and Brachypodium sp. as a fungal-temperate grass pathosystem

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

Rabe, Franziska; Bosch, Jason; Stirnberg, Alexandra

Due to their economic relevance, the study of plant pathogen interactions is of importance. However, elucidating these interactions and their underlying molecular mechanisms remains challenging since both host and pathogen need to be fully genetically accessible organisms. Here we present milestones in the establishment of a new biotrophic model pathosystem: Ustilago bromivora and Brachypodium sp. We provide a complete toolset, including an annotated fungal genome and methods for genetic manipulation of the fungus and its host plant. This toolset will enable researchers to easily study biotrophic interactions at the molecular level on both the pathogen and the host side. Moreover,more » our research on the fungal life cycle revealed a mating type bias phenomenon. U. bromivora harbors a haplo-lethal allele that is linked to one mating type region. As a result, the identified mating type bias strongly promotes inbreeding, which we consider to be a potential speciation driver.« less

A complete toolset for the study of Ustilago bromivora and Brachypodium sp. as a fungal-temperate grass pathosystem

DOE PAGES

Rabe, Franziska; Bosch, Jason; Stirnberg, Alexandra; ...

2016-11-11

Due to their economic relevance, the study of plant pathogen interactions is of importance. However, elucidating these interactions and their underlying molecular mechanisms remains challenging since both host and pathogen need to be fully genetically accessible organisms. Here we present milestones in the establishment of a new biotrophic model pathosystem: Ustilago bromivora and Brachypodium sp. We provide a complete toolset, including an annotated fungal genome and methods for genetic manipulation of the fungus and its host plant. This toolset will enable researchers to easily study biotrophic interactions at the molecular level on both the pathogen and the host side. Moreover,more » our research on the fungal life cycle revealed a mating type bias phenomenon. U. bromivora harbors a haplo-lethal allele that is linked to one mating type region. As a result, the identified mating type bias strongly promotes inbreeding, which we consider to be a potential speciation driver.« less

Identification of Genetic Bases of Vibrio fluvialis Species-Specific Biochemical Pathways and Potential Virulence Factors by Comparative Genomic Analysis

PubMed Central

Lu, Xin; Liang, Weili; Wang, Yunduan; Xu, Jialiang

2014-01-01

Vibrio fluvialis is an important food-borne pathogen that causes diarrheal illness and sometimes extraintestinal infections in humans. In this study, we sequenced the genome of a clinical V. fluvialis strain and determined its phylogenetic relationships with other Vibrio species by comparative genomic analysis. We found that the closest relationship was between V. fluvialis and V. furnissii, followed by those with V. cholerae and V. mimicus. Moreover, based on genome comparisons and gene complementation experiments, we revealed genetic mechanisms of the biochemical tests that differentiate V. fluvialis from closely related species. Importantly, we identified a variety of genes encoding potential virulence factors, including multiple hemolysins, transcriptional regulators, and environmental survival and adaptation apparatuses, and the type VI secretion system, which is indicative of complex regulatory pathways modulating pathogenesis in this organism. The availability of V. fluvialis genome sequences may promote our understanding of pathogenic mechanisms for this emerging pathogen. PMID:24441165

Genetic assignment methods for gaining insight into the management of infectious disease by understanding pathogen, vector, and host movement.

PubMed

Remais, Justin V; Xiao, Ning; Akullian, Adam; Qiu, Dongchuan; Blair, David

2011-04-01

For many pathogens with environmental stages, or those carried by vectors or intermediate hosts, disease transmission is strongly influenced by pathogen, host, and vector movements across complex landscapes, and thus quantitative measures of movement rate and direction can reveal new opportunities for disease management and intervention. Genetic assignment methods are a set of powerful statistical approaches useful for establishing population membership of individuals. Recent theoretical improvements allow these techniques to be used to cost-effectively estimate the magnitude and direction of key movements in infectious disease systems, revealing important ecological and environmental features that facilitate or limit transmission. Here, we review the theory, statistical framework, and molecular markers that underlie assignment methods, and we critically examine recent applications of assignment tests in infectious disease epidemiology. Research directions that capitalize on use of the techniques are discussed, focusing on key parameters needing study for improved understanding of patterns of disease.

A complete toolset for the study of Ustilago bromivora and Brachypodium sp. as a fungal-temperate grass pathosystem

PubMed Central

Rabe, Franziska; Bosch, Jason; Stirnberg, Alexandra; Guse, Tilo; Bauer, Lisa; Seitner, Denise; Rabanal, Fernando A; Czedik-Eysenberg, Angelika; Uhse, Simon; Bindics, Janos; Genenncher, Bianca; Navarrete, Fernando; Kellner, Ronny; Ekker, Heinz; Kumlehn, Jochen; Vogel, John P; Gordon, Sean P; Marcel, Thierry C; Münsterkötter, Martin; Walter, Mathias C; Sieber, Christian MK; Mannhaupt, Gertrud; Güldener, Ulrich; Kahmann, Regine; Djamei, Armin

2016-01-01

Due to their economic relevance, the study of plant pathogen interactions is of importance. However, elucidating these interactions and their underlying molecular mechanisms remains challenging since both host and pathogen need to be fully genetically accessible organisms. Here we present milestones in the establishment of a new biotrophic model pathosystem: Ustilago bromivora and Brachypodium sp. We provide a complete toolset, including an annotated fungal genome and methods for genetic manipulation of the fungus and its host plant. This toolset will enable researchers to easily study biotrophic interactions at the molecular level on both the pathogen and the host side. Moreover, our research on the fungal life cycle revealed a mating type bias phenomenon. U. bromivora harbors a haplo-lethal allele that is linked to one mating type region. As a result, the identified mating type bias strongly promotes inbreeding, which we consider to be a potential speciation driver. DOI: http://dx.doi.org/10.7554/eLife.20522.001 PMID:27835569

Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool.

PubMed

Hoenen, Thomas; Groseth, Allison; Rosenke, Kyle; Fischer, Robert J; Hoenen, Andreas; Judson, Seth D; Martellaro, Cynthia; Falzarano, Darryl; Marzi, Andrea; Squires, R Burke; Wollenberg, Kurt R; de Wit, Emmie; Prescott, Joseph; Safronetz, David; van Doremalen, Neeltje; Bushmaker, Trenton; Feldmann, Friederike; McNally, Kristin; Bolay, Fatorma K; Fields, Barry; Sealy, Tara; Rayfield, Mark; Nichol, Stuart T; Zoon, Kathryn C; Massaquoi, Moses; Munster, Vincent J; Feldmann, Heinz

2016-02-01

Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak.

Using NASA Using Remote Sensing in Public Health Applications

NASA Technical Reports Server (NTRS)

Estes, Sue; Haynes, John

2011-01-01

The Public Health application area focuses on Earth science applications to public health and safety, particularly regarding infectious disease, emergency preparedness and response, and environmental health issues. The application explores issues of toxic and pathogenic exposure, as well as natural and man-made hazards and their effects, for risk characterization/mitigation and improvements to health and safety.

Aerial sketchmapping for monitoring forest conditions in Southern Brazil

Treesearch

Y. M. Malheiros de Oliveira; M. A. Doetzer Rosot; N. B. da Luz; W. M. Ciesla; E.W. Johnson; R. Rhea; J.F. Jr. Penteado

2006-01-01

Aerial sketchmapping is a simple, low cost remote sensing method used for detection and mapping of forest damage caused by biotic agents (insects, pathogens and other pests) and abiotic agents (wind, fire, storms, hurricane, ice storms) in North America. This method was introduced to Brazil in 2001/2002 via a USDA Forest Service/EMBRAPA technical exchange program,...

Aggressiveness Changes in Populations of Didymella pinodes over Winter and Spring Pea Cropping Seasons

PubMed Central

Laloi, G.; Montarry, J.; Guibert, M.; Andrivon, D.; Michot, D.

2016-01-01

ABSTRACT Ascochyta blight, caused by the necrotrophic ascomycete Didymella pinodes, is responsible for severe losses in winter and spring pea crops. Despite different climatic conditions, epidemics on winter and spring crops are due to a single population of D. pinodes, suggesting gene flow either between the two crops or from reservoir sources during the cropping season. This should lead to similar pathogenicity characteristics in isolates sampled from the two crops. However, these hypotheses have never been formally tested. We therefore sampled a total of 520 D. pinodes strains throughout a growing season from winter and spring pea plots (WP and SP, respectively) and from winter and spring trap plants (TWP and TSP). Amplified fragment length polymorphism (AFLP) markers revealed high genetic diversity within subpopulations, whereas pathogenicity tests showed that mean aggressiveness increases over the course of an epidemic. These results support the idea that alloinoculum contributes to the carryover of epidemics between winter and spring crops and that the most aggressive isolates are selected as an epidemic progresses. IMPORTANCE Ascochyta blight, caused by Didymella pinodes, is responsible for severe losses in pea crops. While previous studies have shown that ascochyta blight epidemics on winter and spring crops are due to a single population of D. pinodes, suggesting that isolates from the two crops present similar pathogenicity characteristics, that hypothesis have never been tested. Genetic analysis of subpopulations sampled throughout a growing season from winter and spring pea plots revealed high genetic diversity within subpopulations, whereas pathogenicity tests showed that mean aggressiveness increases over the course of an epidemic. PMID:27208102

Phylogeny and variability of Colletotrichum truncatum associated with soybean anthracnose in Brazil.

PubMed

Rogério, F; Ciampi-Guillardi, M; Barbieri, M C G; Bragança, C A D; Seixas, C D S; Almeida, A M R; Massola, N S

2017-02-01

Fungal diseases are among the main factors limiting high yields of soybean crop. Colletotrichum isolates from soybean plants with anthracnose symptoms were studied from different regions and time periods in Brazil using molecular, morphological and pathogenic analyses. Bayesian phylogenetic inference of GAPDH, HIS3 and ITS-5.8S rDNA sequences, the morphologies of colony and conidia, and inoculation tests on seeds and seedlings were performed. All isolates clustered only with Colletotrichum truncatum species in three well-separated clusters. Intraspecific genetic diversity revealed 27 distinct haplotypes in 51 fungal isolates; some of which were identical to C. truncatum sequences from other regions around the world, while others were related to alternative hosts. Conidia were falcate, hyaline, unicellular and aseptate, formed in acervuli, with variable dimensions. Despite being pathogenic to seedlings by both inoculation methods, variation was observed in the aggressiveness of the tested isolates, which was not correlated with genetic variation. The identification of C. truncatum in the sampled isolates was evidenced as being the only causal agent of soybean anthracnose in Brazil until 2007, with relevant genetic, morphological and pathogenic variability as well as a broad geographical origin. The wide distribution of the predominant C. truncatum haplotype indicated the existence of a highly efficient mechanism of pathogen dispersal over long distances, reinforcing the role of seeds as the primary source of disease inoculum. The characterization and distribution of Colletotrichum species in soybean-producing regions in Brazil is fundamental for understanding the disease epidemiology and for ensuring effective control strategies against anthracnose. © 2016 The Society for Applied Microbiology.

Molecular Survey of Bacterial Zoonotic Agents in Bats from the Country of Georgia (Caucasus).

PubMed

Bai, Ying; Urushadze, Lela; Osikowicz, Lynn; McKee, Clifton; Kuzmin, Ivan; Kandaurov, Andrei; Babuadze, Giorgi; Natradze, Ioseb; Imnadze, Paata; Kosoy, Michael

2017-01-01

Bats are important reservoirs for many zoonotic pathogens. However, no surveys of bacterial pathogens in bats have been performed in the Caucasus region. To understand the occurrence and distribution of bacterial infections in these mammals, 218 bats belonging to eight species collected from four regions of Georgia were examined for Bartonella, Brucella, Leptospira, and Yersinia using molecular approaches. Bartonella DNA was detected in 77 (35%) bats from all eight species and was distributed in all four regions. The prevalence ranged 6-50% per bat species. The Bartonella DNA represented 25 unique genetic variants that clustered into 21 lineages. Brucella DNA was detected in two Miniopterus schreibersii bats and in two Myotis blythii bats, all of which were from Imereti (west-central region). Leptospira DNA was detected in 25 (13%) bats that included four M. schreibersii bats and 21 M. blythii bats collected from two regions. The Leptospira sequences represented five genetic variants with one of them being closely related to the zoonotic pathogen L. interrogans (98.6% genetic identity). No Yersinia DNA was detected in the bats. Mixed infections were observed in several cases. One M. blythii bat and one M. schreibersii bat were co-infected with Bartonella, Brucella, and Leptospira; one M. blythii bat and one M. schreibersii bat were co-infected with Bartonella and Brucella; 15 M. blythii bats and three M. schreibersii bats were co-infected with Bartonella and Leptospira. Our results suggest that bats in Georgia are exposed to multiple bacterial infections. Further studies are needed to evaluate pathogenicity of these agents to bats and their zoonotic potential.

Genome-Wide Association Study on Resistance to Stalk Rot Diseases in Grain Sorghum

PubMed Central

Adeyanju, Adedayo; Little, Christopher; Yu, Jianming; Tesso, Tesfaye

2015-01-01

Stalk rots are important biotic constraints to sorghum production worldwide. Several pathogens may be associated with the disease, but Macrophomina phaseolina and Fusarium thapsinum are recognized as the major causal organisms. The diseases become more aggressive when drought and high-temperature stress occur during grain filling. Progress in genetic improvement efforts has been slow due to lack of effective phenotyping protocol and the strong environmental effect on disease incidence and severity. Deployment of modern molecular tools is expected to accelerate efforts to develop resistant hybrids. This study was aimed at identifying genomic regions associated with resistance to both causal organisms. A sorghum diversity panel consisting of 300 genotypes assembled from different parts of the world was evaluated for response to infection by both pathogens. Community resources of 79,132 single nucleotide polymorphic (SNP) markers developed on the panel were used in association studies using a multi-locus mixed model to map loci associated with stalk rot resistance. Adequate genetic variation was observed for resistance to both pathogens. Structure analysis grouped the genotypes into five subpopulations primarily based on the racial category of the genotypes. Fourteen loci and a set of candidate genes appear to be involved in connected functions controlling plant defense response. However, each associated SNP had relatively small effect on the traits, accounting for 19–30% of phenotypic variation. Linkage disequilibrium analyses suggest that significant SNPs are genetically independent. Estimation of frequencies of associated alleles revealed that durra and caudatum subpopulations were enriched for resistant alleles, but the results suggest complex molecular mechanisms underlying resistance to both pathogens. PMID:25882062

Using NextRAD sequencing to infer movement of herbivores among host plants.

PubMed

Fu, Zhen; Epstein, Brendan; Kelley, Joanna L; Zheng, Qi; Bergland, Alan O; Castillo Carrillo, Carmen I; Jensen, Andrew S; Dahan, Jennifer; Karasev, Alexander V; Snyder, William E

2017-01-01

Herbivores often move among spatially interspersed host plants, tracking high-quality resources through space and time. This dispersal is of particular interest for vectors of plant pathogens. Existing molecular tools to track such movement have yielded important insights, but often provide insufficient genetic resolution to infer spread at finer spatiotemporal scales. Here, we explore the use of Nextera-tagmented reductively-amplified DNA (NextRAD) sequencing to infer movement of a highly-mobile winged insect, the potato psyllid (Bactericera cockerelli), among host plants. The psyllid vectors the pathogen that causes zebra chip disease in potato (Solanum tuberosum), but understanding and managing the spread of this pathogen is limited by uncertainty about the insect's host plant(s) outside of the growing season. We identified 1,978 polymorphic loci among psyllids separated spatiotemporally on potato or in patches of bittersweet nightshade (S. dulcumara), a weedy plant proposed to be the source of potato-colonizing psyllids. A subset of the psyllids on potato exhibited genetic similarity to insects on nightshade, consistent with regular movement between these two host plants. However, a second subset of potato-collected psyllids was genetically distinct from those collected on bittersweet nightshade; this suggests that a currently unrecognized source, i.e., other nightshade patches or a third host-plant species, could be contributing to psyllid populations in potato. Oftentimes, dispersal of vectors of pathogens must be tracked at a fine scale in order to understand, predict, and manage disease spread. We demonstrate that emerging sequencing technologies that detect genome-wide SNPs of a vector can be used to infer such localized movement.

Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus

PubMed Central

Lowder, Bethan V.; Guinane, Caitriona M.; Ben Zakour, Nouri L.; Weinert, Lucy A.; Conway-Morris, Andrew; Cartwright, Robyn A.; Simpson, A. John; Rambaut, Andrew; Nübel, Ulrich; Fitzgerald, J. Ross

2009-01-01

The impact of globalization on the emergence and spread of pathogens is an important veterinary and public health issue. Staphylococcus aureus is a notorious human pathogen associated with serious nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry, which are a large economic burden on the global broiler chicken industry. Here, we provide evidence that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump that occurred approximately 38 years ago (range, 30 to 63 years ago) by a subtype of the worldwide human ST5 clonal lineage unique to Poland. In contrast to human subtypes of the ST5 radiation, which demonstrate strong geographic clustering, the poultry ST5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. The poultry ST5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. These genetic events have resulted in enhanced resistance to killing by chicken heterophils, reflecting avian host-adaptive evolution. Taken together, we have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens. PMID:19884497

Molecular Survey of Bacterial Zoonotic Agents in Bats from the Country of Georgia (Caucasus)

PubMed Central

Osikowicz, Lynn; McKee, Clifton; Kuzmin, Ivan; Kandaurov, Andrei; Babuadze, Giorgi; Natradze, Ioseb; Imnadze, Paata; Kosoy, Michael

2017-01-01

Bats are important reservoirs for many zoonotic pathogens. However, no surveys of bacterial pathogens in bats have been performed in the Caucasus region. To understand the occurrence and distribution of bacterial infections in these mammals, 218 bats belonging to eight species collected from four regions of Georgia were examined for Bartonella, Brucella, Leptospira, and Yersinia using molecular approaches. Bartonella DNA was detected in 77 (35%) bats from all eight species and was distributed in all four regions. The prevalence ranged 6–50% per bat species. The Bartonella DNA represented 25 unique genetic variants that clustered into 21 lineages. Brucella DNA was detected in two Miniopterus schreibersii bats and in two Myotis blythii bats, all of which were from Imereti (west-central region). Leptospira DNA was detected in 25 (13%) bats that included four M. schreibersii bats and 21 M. blythii bats collected from two regions. The Leptospira sequences represented five genetic variants with one of them being closely related to the zoonotic pathogen L. interrogans (98.6% genetic identity). No Yersinia DNA was detected in the bats. Mixed infections were observed in several cases. One M. blythii bat and one M. schreibersii bat were co-infected with Bartonella, Brucella, and Leptospira; one M. blythii bat and one M. schreibersii bat were co-infected with Bartonella and Brucella; 15 M. blythii bats and three M. schreibersii bats were co-infected with Bartonella and Leptospira. Our results suggest that bats in Georgia are exposed to multiple bacterial infections. Further studies are needed to evaluate pathogenicity of these agents to bats and their zoonotic potential. PMID:28129398