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Molecular Plant Pathology Jan 2009Successful host-pathogen interactions require the presence, maintenance and expression of gene cassettes called 'pathogenicity islands' (PAIs) and 'metabolic islands'... (Review)
Review
Successful host-pathogen interactions require the presence, maintenance and expression of gene cassettes called 'pathogenicity islands' (PAIs) and 'metabolic islands' (MAIs) in the respective pathogen. The products of these genes confer on the pathogen the means to recognize their host(s) and to efficiently evade host defences in order to colonize, propagate within the host and eventually disseminate from the host. Virulence effectors secreted by type III and type IV secretion systems, among others, play vital roles in sustaining pathogenicity and optimizing host-pathogen interactions. Complete genome sequences of plant pathogenic bacteria have revealed the presence of PAIs and MAIs. The genes of these islands possess mosaic structures with regions displaying differences in nucleotide composition and codon usage in relation to adjacent genome structures, features that are highly suggestive of their acquisition from a foreign donor. These donors can be other bacteria, as well as lower members of the Archaea and Eukarya. Genes that have moved from the domains Archaea and Eukarya to the domain Bacteria are true cases of horizontal gene transfer. They represent interdomain genetic transfer. Genetic exchange between distinct members of the domain Bacteria, however, represents lateral gene transfer, an intradomain event. Both horizontal and lateral gene transfer events have been used to facilitate survival fitness of the pathogen.
Topics: Bacteria; Gene Transfer, Horizontal; Genes, Plant; Plants; Virulence
PubMed: 19161360
DOI: 10.1111/j.1364-3703.2008.00518.x -
Nature Communications Jan 2023Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the...
Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring the diversity of a barcoded population of the diarrhea causing bacterium Citrobacter rodentium during colonization of its natural host, mice, we determine the number of cells that found the infection by establishing a replicative niche. In female mice the size of the pathogen's founding population scales with dose and is controlled by a severe yet slow-acting bottleneck. Reducing stomach acid or changing host genotype modestly relaxes the bottleneck without breaking the fractional relationship between dose and founders. In contrast, disrupting the microbiota causes the founding population to no longer scale with the size of the inoculum and allows the pathogen to infect at almost any dose, indicating that the microbiota creates the dominant bottleneck. Further, in the absence of competition with the microbiota, the diversity of the pathogen population slowly contracts as the population is overtaken by bacteria having lost the critical virulence island, the locus of enterocyte effacement (LEE). Collectively, our findings reveal that the mechanisms of protection by colonization bottlenecks are reflected in and can be generally defined by the impact of dose on the pathogen's founding population.
Topics: Female; Animals; Mice; Virulence; Bacteria; Virulence Factors; Enterocytes; Diarrhea; Citrobacter rodentium; Enterobacteriaceae Infections
PubMed: 36709326
DOI: 10.1038/s41467-023-36162-3 -
Molecular Plant Pathology Jul 2021Plant-pathogenic fungi are a significant threat to economic and food security worldwide. Novel protection strategies are required and therefore it is critical we... (Review)
Review
Plant-pathogenic fungi are a significant threat to economic and food security worldwide. Novel protection strategies are required and therefore it is critical we understand the mechanisms by which these pathogens cause disease. Virulence factors and pathogenicity genes have been identified, but in many cases their roles remain elusive. It is becoming increasingly clear that gene regulation is vital to enable plant infection and transcription factors play an essential role. Efforts to determine their regulatory functions in plant-pathogenic fungi have expanded since the annotation of fungal genomes revealed the ubiquity of transcription factors from a broad range of families. This review establishes the significance of transcription factors as regulatory elements in plant-pathogenic fungi and provides a systematic overview of those that have been functionally characterized. Detailed analysis is provided on regulators from well-characterized families controlling various aspects of fungal metabolism, development, stress tolerance, and the production of virulence factors such as effectors and secondary metabolites. This covers conserved transcription factors with either specialized or nonspecialized roles, as well as recently identified regulators targeting key virulence pathways. Fundamental knowledge of transcription factor regulation in plant-pathogenic fungi provides avenues to identify novel virulence factors and improve our understanding of the regulatory networks linked to pathogen evolution, while transcription factors can themselves be specifically targeted for disease control. Areas requiring further insight regarding the molecular mechanisms and/or specific classes of transcription factors are identified, and direction for future investigation is presented.
Topics: Fungal Proteins; Fungi; Gene Expression Regulation, Fungal; Genome, Fungal; Plant Diseases; Plants; Transcription Factors; Virulence; Virulence Factors
PubMed: 33973705
DOI: 10.1111/mpp.13056 -
The New Phytologist Aug 2009Ecological, evolutionary and molecular models of interactions between plant hosts and microbial pathogens are largely based around a concept of tightly coupled... (Review)
Review
Ecological, evolutionary and molecular models of interactions between plant hosts and microbial pathogens are largely based around a concept of tightly coupled interactions between species pairs. However, highly pathogenic and obligate associations between host and pathogen species represent only a fraction of the diversity encountered in natural and managed systems. Instead, many pathogens can infect a wide range of hosts, and most hosts are exposed to more than one pathogen species, often simultaneously. Furthermore, outcomes of pathogen infection vary widely because host plants vary in resistance and tolerance to infection, while pathogens are also variable in their ability to grow on or within hosts. Environmental heterogeneity further increases the potential for variation in plant host-pathogen interactions by influencing the degree and fitness consequences of infection. Here, we describe these continua of specificity and virulence inherent within plant host-pathogen interactions. Using this framework, we describe and contrast the genetic and environmental mechanisms that underlie this variation, outline consequences for epidemiology and community structure, explore likely ecological and evolutionary drivers, and highlight several key areas for future research.
Topics: Biological Evolution; Ecosystem; Host-Pathogen Interactions; Plants; Species Specificity; Virulence
PubMed: 19563451
DOI: 10.1111/j.1469-8137.2009.02927.x -
Molecular Genetics and Genomics : MGG Nov 2022The current pandemic (COVID-19) has made evident the need to approach pathogenicity from a deeper and more systematic perspective that might lead to methodologies to...
The current pandemic (COVID-19) has made evident the need to approach pathogenicity from a deeper and more systematic perspective that might lead to methodologies to quickly predict new strains of microbes that could be pathogenic to humans. Here we propose as a solution a general and principled definition of pathogenicity that can be practically implemented in operational ways in a framework for characterizing and assessing the (degree of) potential pathogenicity of a microbe to a given host (e.g., a human individual) just based on DNA biomarkers, and to the point of predicting its impact on a host a priori to a meaningful degree of accuracy. The definition is based on basic biochemistry, the Gibbs free Energy of duplex formation between oligonucleotides and some deep structural properties of DNA revealed by an approximation with certain properties. We propose two operational tests based on the nearest neighbor (NN) model of the Gibbs Energy and an approximating metric (the h-distance.) Quality assessments demonstrate that these tests predict pathogenicity with an accuracy of over 80%, and sensitivity and specificity over 90%. Other tests obtained by training machine learning models on deep features extracted from DNA sequences yield scores of 90% for accuracy, 100% for sensitivity and 80% for specificity. These results hint towards the possibility of an operational, objective, and general conceptual framework for prior identification of pathogens and their impact without the cost of death or sickness in a host (e.g., humans.) Consequently, a reasonable prediction of possible pathogens might pave the way to eventually transform the way we handle and prepare for future pandemic events and mitigate the adverse impact on human health, while reducing the number of clinical trials to obtain similar results.
Topics: Humans; Virulence; COVID-19; Oligonucleotides; DNA; Biomarkers
PubMed: 36125534
DOI: 10.1007/s00438-022-01951-w -
PeerJ 2022Obligate fungal pathogens (ascomycetes and basidiomycetes) and oomycetes are known to cause diseases in cereal crop plants. They feed on living cells and most of them... (Review)
Review
Obligate fungal pathogens (ascomycetes and basidiomycetes) and oomycetes are known to cause diseases in cereal crop plants. They feed on living cells and most of them have learned to bypass the host immune machinery. This paper discusses some of the factors that are associated with pathogenicity drawing examples from ascomycetes, basidiomycetes and oomycetes, with respect to their manifestation in crop plants. The comparisons have revealed a striking similarity in the three groups suggesting convergent pathways that have arisen from three lineages independently leading to an obligate lifestyle. This review has been written with the intent, that new information on adaptation strategies of biotrophs, modifications in pathogenicity strategies and population dynamics will improve current strategies for breeding with stable resistance.
Topics: Virulence; Plant Breeding; Oomycetes; Adaptation, Physiological; Ascomycota
PubMed: 36042858
DOI: 10.7717/peerj.13794 -
Virulence Dec 2023Cysteiniphilum is a newly discovered genus in 2017 and is phylogenetically closely related to highly pathogenic . Recently, it has become an emerging pathogen in humans....
Cysteiniphilum is a newly discovered genus in 2017 and is phylogenetically closely related to highly pathogenic . Recently, it has become an emerging pathogen in humans. However, the complete genome sequence of genus Cysteiniphilum is lacking, and the genomic characteristics of genetic diversity, evolutionary dynamics, and pathogenicity have not been characterized. In this study, the complete genome of the first reported clinical isolate QT6929 of genus Cysteiniphilum was sequenced, and comparative genomics analyses to Francisella genus were conducted to unveil the genomic landscape and diversity of the genus Cysteiniphilum. Our results showed that the complete genome of QT6929 consists of one 2.61 Mb chromosome and a 76,819 bp plasmid. The calculated average nucleotide identity and DNA-DNA hybridization values revealed that two clinical isolates QT6929 and JM-1 should be reclassified as two novel species in genus Cysteiniphilum. Pan-genome analysis revealed genomic diversity within the genus Cysteiniphilum and an open pan-genome state. Genomic plasticity analysis exhibited abundant mobile genetic elements including genome islands, insertion sequences, prophages, and plasmids on Cysteiniphilum genomes, which facilitated the broad exchange of genetic material between Cysteiniphilum and other genera like Francisella and Legionella. Several potential virulence genes associated with lipopolysaccharide/lipooligosaccharide, capsule, and haem biosynthesis specific to clinical isolates were predicted and might contribute to their pathogenicity in humans. Incomplete Francisella pathogenicity island was identified in most Cysteiniphilum genomes. Overall, our study provides an updated phylogenomic relationship of members of the genus Cysteiniphilum and comprehensive genomic insights into this rare emerging pathogen.
Topics: Humans; Virulence; Genome, Bacterial; Francisella tularensis; Phylogeny; Genomics; DNA Transposable Elements; Genetic Variation
PubMed: 37246787
DOI: 10.1080/21505594.2023.2214416 -
Virulence Dec 2019Opportunistic commensal and environmental fungi can cause superficial to systemic diseases in humans. But how did these pathogens adapt to infect us and how does... (Review)
Review
Opportunistic commensal and environmental fungi can cause superficial to systemic diseases in humans. But how did these pathogens adapt to infect us and how does host-pathogen co-evolution shape their virulence potential? During evolution toward pathogenicity, not only do microorganisms gain virulence genes, but they also tend to lose non-adaptive genes in the host niche. Additionally, virulence factors can become detrimental during infection when they trigger host recognition. The loss of non-adaptive genes as well as the loss of the virulence potential of genes by adaptations to the host has been investigated in pathogenic bacteria and phytopathogenic fungi, where they are known as antivirulence and avirulence genes, respectively. However, these concepts are nearly unknown in the field of pathogenic fungi of humans. We think that this unnecessarily limits our view of human-fungal interplay, and that much could be learned if we applied a similar framework to aspects of these interactions. In this review, we, therefore, define and adapt the concepts of antivirulence and avirulence genes for human pathogenic fungi. We provide examples for analogies to antivirulence genes of bacterial pathogens and to avirulence genes of phytopathogenic fungi. Introducing these terms to the field of pathogenic fungi of humans can help to better comprehend the emergence and evolution of fungal virulence and disease.
Topics: Adaptation, Physiological; Animals; Evolution, Molecular; Fungi; Genes, Fungal; Host-Pathogen Interactions; Humans; Mice; Virulence; Virulence Factors
PubMed: 31711357
DOI: 10.1080/21505594.2019.1688753 -
Cell Feb 2006The availability of hundreds of bacterial genome sequences has altered the study of bacterial pathogenesis, affecting both design of experiments and analysis of results.... (Review)
Review
The availability of hundreds of bacterial genome sequences has altered the study of bacterial pathogenesis, affecting both design of experiments and analysis of results. Comparative genomics and genomic tools have been used to identify virulence factors and genes involved in environmental persistence of pathogens. However, a major stumbling block in the genomics revolution has been the large number of genes with unknown function that have been identified in every organism sequenced to date.
Topics: Bacteria; Computational Biology; Evolution, Molecular; Genetic Variation; Genome, Bacterial; Genomics; Humans; Models, Genetic; Oligonucleotide Array Sequence Analysis; Proteomics; Sequence Analysis; Virulence; Virulence Factors
PubMed: 16497582
DOI: 10.1016/j.cell.2006.02.002 -
Virulence 2014Until quite recently and since the late 19(th) century, medical microbiology has been based on the assumption that some micro-organisms are pathogens and others are not.... (Review)
Review
Until quite recently and since the late 19(th) century, medical microbiology has been based on the assumption that some micro-organisms are pathogens and others are not. This binary view is now strongly criticized and is even becoming untenable. We first provide a historical overview of the changing nature of host-parasite interactions, in which we argue that large-scale sequencing not only shows that identifying the roots of pathogenesis is much more complicated than previously thought, but also forces us to reconsider what a pathogen is. To address the challenge of defining a pathogen in post-genomic science, we present and discuss recent results that embrace the microbial genetic diversity (both within- and between-host) and underline the relevance of microbial ecology and evolution. By analyzing and extending earlier work on the concept of pathogen, we propose pathogenicity (or virulence) should be viewed as a dynamical feature of an interaction between a host and microbes.
Topics: Animals; Bacteria; Biological Evolution; Fungi; Genetic Variation; Host-Parasite Interactions; Host-Pathogen Interactions; Humans; Virulence; Viruses
PubMed: 25483864
DOI: 10.4161/21505594.2014.960726