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Cell Host & Microbe May 2016Protozoan parasites colonize numerous metazoan hosts and insect vectors through their life cycles, with the need to respond quickly and reversibly while encountering... (Review)
Review
Protozoan parasites colonize numerous metazoan hosts and insect vectors through their life cycles, with the need to respond quickly and reversibly while encountering diverse and often hostile ecological niches. To succeed, parasites must also persist within individuals until transmission between hosts is achieved. Several parasitic protozoa cause a huge burden of disease in humans and livestock, and here we focus on the parasites that cause malaria and African trypanosomiasis. Efforts to understand how these pathogens adapt to survive in varied host environments, cause disease, and transmit between hosts have revealed a wealth of epigenetic phenomena. Epigenetic switching mechanisms appear to be ideally suited for the regulation of clonal antigenic variation underlying successful parasitism. We review the molecular players and complex mechanistic layers that mediate the epigenetic regulation of virulence gene expression. Understanding epigenetic processes will aid the development of antiparasitic therapeutics.
Topics: Animals; Gene Expression Regulation; Humans; Parasites; Virulence
PubMed: 27173931
DOI: 10.1016/j.chom.2016.04.020 -
Molecular Plant Pathology Jun 2017Plant-pathogenic fungi cause diseases to all major crop plants world-wide and threaten global food security. Underpinning fungal diseases are virulence genes... (Review)
Review
Plant-pathogenic fungi cause diseases to all major crop plants world-wide and threaten global food security. Underpinning fungal diseases are virulence genes facilitating plant host colonization that often marks pathogenesis and crop failures, as well as an increase in staple food prices. Fungal molecular genetics is therefore the cornerstone to the sustainable prevention of disease outbreaks. Pathogenicity studies using mutant collections provide immense function-based information regarding virulence genes of economically relevant fungi. These collections are rich in potential targets for existing and new biological control agents. They contribute to host resistance breeding against fungal pathogens and are instrumental in searching for novel resistance genes through the identification of fungal effectors. Therefore, functional analyses of mutant collections propel gene discovery and characterization, and may be incorporated into disease management strategies. In the light of these attributes, mutant collections enhance the development of practical solutions to confront modern agricultural constraints. Here, a critical review of mutant collections constructed by various laboratories during the past decade is provided. We used Magnaporthe oryzae and Fusarium graminearum studies to show how mutant screens contribute to bridge existing knowledge gaps in pathogenicity and fungal-host interactions.
Topics: Fungal Proteins; Fungi; Fusarium; Genome, Fungal; Host-Pathogen Interactions; Magnaporthe; Plant Diseases; Plants; Virulence
PubMed: 27733021
DOI: 10.1111/mpp.12497 -
Genome Biology and Evolution May 2016Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce...
Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen-host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus-animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation.
Topics: Animals; Ascomycota; Evolution, Molecular; Genome, Fungal; Humans; Insecta; Plant Diseases; Plants; Virulence; Virulence Factors
PubMed: 27071652
DOI: 10.1093/gbe/evw082 -
Advances in Experimental Medicine and... 2011The family Xanthomonadaceae is a wide-spread family of bacteria belonging to the gamma subdivision of the Gram-negative proteobacteria, including the two... (Review)
Review
The family Xanthomonadaceae is a wide-spread family of bacteria belonging to the gamma subdivision of the Gram-negative proteobacteria, including the two plant-pathogenic genera Xanthomonas and Xylella, and the related genus Stenotrophomonas. Adhesion is a widely conserved virulence mechanism among Gram-negative bacteria, no matter whether they are human, animal or plant pathogens, since attachment to the host tissue is one of the key early steps of the bacterial infection process. Bacterial attachment to surfaces is mediated by surface structures that are anchored in the bacterial outer membrane and cover a broad group of fimbrial and non-fimbrial structures, commonly known as adhesins. In this chapter, we discuss recent findings on candidate adhesins of plant-pathogenic Xanthomonadaceae, including polysaccharidic (lipopolysaccharides, exopolysaccharides) and proteineous structures (chaperone/usher pili, type IV pili, autotransporters, two-partner-secreted and other outer membrane adhesins), their involvement in the formation of biofilms and their mode of regulation via quorum sensing. We then compare the arsenals of adhesins among different Xanthomonas strains and evaluate their mode of selection. Finally, we summarize the sparse knowledge on specific adhesin receptors in plants and the possible role of RGD motifs in binding to integrin-like plant molecules.
Topics: Adhesins, Bacterial; Bacterial Adhesion; Fimbriae, Bacterial; Gram-Negative Bacterial Infections; Host-Pathogen Interactions; Plant Diseases; Plants; Polysaccharides, Bacterial; Receptors, Immunologic; Virulence; Xanthomonadaceae
PubMed: 21557058
DOI: 10.1007/978-94-007-0940-9_5 -
Frontiers in Cellular and Infection... 2017Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid... (Review)
Review
Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid organism would be a recent gene duplication event, prior to divergence through selective pressure. However, a growing number of examples exist where an organism encodes two genes that appear to perform the same function. For example, many pathogens translocate multiple effector proteins into hosts. While disruption of individual effector genes does not result in a discernable phenotype, deleting genes in combination impairs pathogenesis: this has been described as redundancy. In many cases, this apparent redundancy could be due to limitations of laboratory models of pathogenesis that do not fully recapitulate the disease process. Alternatively, it is possible that the selective advantage achieved by this perceived redundancy is too subtle to be measured in the laboratory. Moreover, there are numerous possibilities for different types of redundancy. The most common and recognized form of redundancy is functional redundancy whereby two proteins have similar biochemical activities and substrate specificities allowing each one to compensate in the absence of the other. However, redundancy can also exist between seemingly unrelated proteins that manipulate the same or complementary host cell pathways. In this article, we outline 5 types of redundancy in pathogenesis: molecular, target, pathway, cellular process, and system redundancy that incorporate the biochemical activities, the host target specificities and the impact of effector function on the pathways and cellular process they modulate. For each type of redundancy, we provide examples from pathogenesis as this organism employs over 300 secreted virulence proteins and loss of individual proteins rarely impacts intracellular growth. We also discuss selective pressures that drive the maintenance of redundant mechanisms, the current methods used to resolve redundancy and features that distinguish between redundant and non-redundant virulence mechanisms.
Topics: Bacterial Proteins; Gene Duplication; Genes, Bacterial; Host-Pathogen Interactions; Humans; Legionella; Legionella pneumophila; Legionellosis; Mutagenesis, Insertional; Phenotype; Transcription Factors; Virulence
PubMed: 29188194
DOI: 10.3389/fcimb.2017.00467 -
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 -
Parasite Immunology Feb 2023We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune... (Review)
Review
We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune defences to clear infecting fungal cells versus the success of the fungus in mounting compensatory adaptive responses. As each seeks to gain advantage during these skirmishes, the interactions between host and fungal pathogen are complex and dynamic. Nevertheless, simply compromising the physiological robustness of fungal pathogens reduces their ability to evade antifungal immunity, their virulence, and their tolerance against antifungal therapy. In this article I argue that this physiological robustness is based on a 'Resilience Network' which mechanistically links and controls fungal growth, metabolism, stress resistance and drug tolerance. The elasticity of this network probably underlies the phenotypic variability of fungal isolates and the heterogeneity of individual cells within clonal populations. Consequently, I suggest that the definition of the fungal Resilience Network represents an important goal for the future which offers the clear potential to reveal drug targets that compromise drug tolerance and synergise with current antifungal therapies.
Topics: Antifungal Agents; Virulence; Host-Pathogen Interactions
PubMed: 35962618
DOI: 10.1111/pim.12946 -
The New Phytologist 2009Many biotrophic fungal and oomycete pathogens share a common infection process involving the formation of haustoria, which penetrate host cell walls and form a close... (Review)
Review
Many biotrophic fungal and oomycete pathogens share a common infection process involving the formation of haustoria, which penetrate host cell walls and form a close association with plant membranes. Recent studies have identified a class of pathogenicity effector proteins from these pathogens that is transferred into host cells from haustoria during infection. This insight stemmed from the identification of avirulence (Avr) proteins from these pathogens that are recognized by intracellular host resistance (R) proteins. Oomycete effectors contain a conserved translocation motif that directs their uptake into host cells independently of the pathogen, and is shared with the human malaria pathogen. Genome sequence information indicates that oomycetes may express several hundred such host-translocated effectors. Elucidating the transport mechanism of fungal and oomycete effectors and their roles in disease offers new opportunities to understand how these pathogens are able to manipulate host cells to establish a parasitic relationship and to develop new disease-control measures.
Topics: Algal Proteins; Amino Acid Motifs; Animals; Base Sequence; Biological Transport; Fungal Proteins; Fungi; Genome; Host-Pathogen Interactions; Humans; Oomycetes; Plant Diseases; Plants; Plasmodium falciparum; Translocation, Genetic; Virulence
PubMed: 19558422
DOI: 10.1111/j.1469-8137.2009.02922.x -
European Journal of Clinical... Nov 2013Streptococcus infections are still one of the important problems facing contemporary medicine. As the World Health Organization (WHO) warns, Streptococcus pneumoniae is... (Review)
Review
Streptococcus infections are still one of the important problems facing contemporary medicine. As the World Health Organization (WHO) warns, Streptococcus pneumoniae is responsible for the highest number of pneumonia cases all over the world. Despite an increasing number of pneumococcal vaccinations, incidences of disease connected to this pathogen's infection stay at the same level, which is related to a constantly increasing number of infections caused by nonvaccinal serotypes. Unfortunately, the pathogenicity of bacteria of the Streptococcus genus is also connected to species considered to be physiological flora in humans or animals and, additionally, new species exhibiting pathogenic potential have been discovered. This paper presents an opinion concerning the epidemiology of streptococci infections based on case studies and other publications devoted to this problem. It also sheds new light based on recent reports on the prevention of protective vaccinations application in the case of streptococci infections.
Topics: Global Health; Humans; Prevalence; Streptococcal Infections; Streptococcus pneumoniae; Virulence
PubMed: 24141975
DOI: 10.1007/s10096-013-1914-9 -
European Journal of Clinical... Nov 2017In recent years, whole-genome sequencing (WGS) has been perceived as a technology with the potential to revolutionise clinical microbiology. Herein, we reviewed the... (Review)
Review
In recent years, whole-genome sequencing (WGS) has been perceived as a technology with the potential to revolutionise clinical microbiology. Herein, we reviewed the literature on the use of WGS for the most commonly encountered pathogens in clinical microbiology laboratories: Escherichia coli and other Enterobacteriaceae, Staphylococcus aureus and coagulase-negative staphylococci, streptococci and enterococci, mycobacteria and Chlamydia trachomatis. For each pathogen group, we focused on five different aspects: the genome characteristics, the most common genomic approaches and the clinical uses of WGS for (i) typing and outbreak analysis, (ii) virulence investigation and (iii) in silico antimicrobial susceptibility testing. Of all the clinical usages, the most frequent and straightforward usage was to type bacteria and to trace outbreaks back. A next step toward standardisation was made thanks to the development of several new genome-wide multi-locus sequence typing systems based on WGS data. Although virulence characterisation could help in various particular clinical settings, it was done mainly to describe outbreak strains. An increasing number of studies compared genotypic to phenotypic antibiotic susceptibility testing, with mostly promising results. However, routine implementation will preferentially be done in the workflow of particular pathogens, such as mycobacteria, rather than as a broadly applicable generic tool. Overall, concrete uses of WGS in routine clinical microbiology or infection control laboratories were done, but the next big challenges will be the standardisation and validation of the procedures and bioinformatics pipelines in order to reach clinical standards.
Topics: Bacteria; Base Sequence; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Multilocus Sequence Typing; Virulence
PubMed: 28639162
DOI: 10.1007/s10096-017-3024-6