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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 -
Proceedings of the National Academy of... Jul 2023Encounters between host cells and intracellular bacterial pathogens lead to complex phenotypes that determine the outcome of infection. Single-cell RNA sequencing...
Encounters between host cells and intracellular bacterial pathogens lead to complex phenotypes that determine the outcome of infection. Single-cell RNA sequencing (scRNA-seq) is increasingly used to study the host factors underlying diverse cellular phenotypes but has limited capacity to analyze the role of bacterial factors. Here, we developed scPAIR-seq, a single-cell approach to analyze infection with a pooled library of multiplex-tagged, barcoded bacterial mutants. Infected host cells and barcodes of intracellular bacterial mutants are both captured by scRNA-seq to functionally analyze mutant-dependent changes in host transcriptomes. We applied scPAIR-seq to macrophages infected with a library of Typhimurium secretion system effector mutants. We analyzed redundancy between effectors and mutant-specific unique fingerprints and mapped the global virulence network of each individual effector by its impact on host immune pathways. ScPAIR-seq is a powerful tool to untangle bacterial virulence strategies and their complex interplay with host defense strategies that drive infection outcome.
Topics: Virulence; Salmonella typhimurium; Macrophages; Virulence Factors; Bacterial Proteins; Host-Pathogen Interactions
PubMed: 37399397
DOI: 10.1073/pnas.2218812120 -
International Journal of Molecular... Aug 2023is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through...
is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through a forward genetic screen combined with next-generation sequencing, a putative protein kinase, Cak1, was found to be involved in the growth and pathogenicity of . Knockout and complementation experiments confirmed that deletions in caused defects in mycelium and sclerotia development, as well as appressoria formation and host penetration, leading to complete loss of virulence. These findings suggest that Cak1 is essential for the growth, development, and pathogenicity of . Therefore, Cak1 could serve as a potential target for the control of infection through host-induced gene silencing (HIGS), which could increase crop resistance to the pathogen.
Topics: Virulence; Ascomycota; Gene Silencing; High-Throughput Nucleotide Sequencing
PubMed: 37628791
DOI: 10.3390/ijms241612610 -
Microbiological Research Jan 2021Candida auris is a worrisome fungal pathogen of humans which emerged merely about a decade ago. Ever since then the scientific community worked hard to understand... (Review)
Review
Candida auris is a worrisome fungal pathogen of humans which emerged merely about a decade ago. Ever since then the scientific community worked hard to understand clinically relevant traits, such as virulence factors, antifungal resistance mechanisms, and its ability to adhere to human skin and medical devices. Whole-genome sequencing of clinical isolates and epidemiological studies outlining the path of nosocomial outbreaks have been the focus of research into this pathogenic and multidrug-resistant yeast since its first description in 2009. More recently, work was started by several laboratories to explore the biology of C. auris. Here, we review the insights of studies characterizing the mechanisms underpinning antifungal drug resistance, biofilm formation, morphogenetic switching, cell aggregation, virulence, and pathogenicity of C. auris. We conclude that, although some progress has been made, there is still a long journey ahead of us, before we fully understand this novel pathogen. Critically important is the development of molecular tools for C. auris to make this fungus genetically tractable and traceable. This will allow an in-depth molecular dissection of the life cycle of C. auris, of its characteristics while interacting with the human host, and the mechanisms it employs to avoid being killed by antifungals and the immune system.
Topics: Antifungal Agents; Biofilms; Candida; Candidiasis; Drug Resistance, Fungal; Fungi; Humans; Microbial Sensitivity Tests; Mutation; Phenotype; Transcriptome; Virulence; Virulence Factors; Whole Genome Sequencing
PubMed: 33096325
DOI: 10.1016/j.micres.2020.126621 -
Molecular Plant-microbe Interactions :... Apr 2023The endomembrane system, extending from the nuclear envelope to the plasma membrane, is critical to the plant response to pathogen infection. Synthesis and transport of... (Review)
Review
The endomembrane system, extending from the nuclear envelope to the plasma membrane, is critical to the plant response to pathogen infection. Synthesis and transport of immunity-related proteins and antimicrobial compounds to and from the plasma membrane are supported by conventional and unconventional processes of secretion and internalization of vesicles, guided by the cytoskeleton networks. Although plant bacterial pathogens reside mostly in the apoplast, major structural and functional modifications of the endomembrane system in the host cell occur during bacterial infection. Here, we review the dynamics of these cellular compartments, briefly, for their essential contributions to the plant defense responses and, in parallel, for their emerging roles in bacterial pathogenicity. We further focus on , spp., and type III secreted effectors that one or both localize to and associate with components of the host endomembrane system or the cytoskeleton network to highlight the diversity of virulence strategies deployed by bacterial pathogens beyond the inhibition of the secretory pathway. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Topics: Bacterial Proteins; Bacteria; Plants; Virulence; Pseudomonas syringae; Plant Diseases
PubMed: 36645655
DOI: 10.1094/MPMI-09-22-0190-FI -
Proceedings of the National Academy of... Nov 2023The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can...
The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of , a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of is yet to be fully realized.
Topics: Animals; Humans; Swine; Streptococcal Infections; Farms; Swine Diseases; Virulence; Streptococcus suis; Livestock
PubMed: 37963246
DOI: 10.1073/pnas.2307773120 -
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 -
Microbiology Spectrum Dec 2023causes life-threatening invasive hospital- and community-associated infections that are usually associated with multidrug resistance globally. Although infections...
causes life-threatening invasive hospital- and community-associated infections that are usually associated with multidrug resistance globally. Although infections cause opportunistic infections typically associated with antibiotic use, immunocompromised immune status, and other factors, they also possess an arsenal of virulence factors crucial for their pathogenicity. Despite this, the relative contribution of these virulence factors and other genetic changes to the pathogenicity of strains remain poorly understood. Here, we investigated whether specific genomic changes in the genome of isolates influence its pathogenicity-infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection and intestinal colonization. Our findings indicate that genetics partially influence the infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection, possibly due to gut-to-bloodstream translocation, highlighting the potential substantial role of host and environmental factors, including gut microbiota, on the opportunistic pathogenic lifestyle of this bacterium.
Topics: Humans; Enterococcus faecalis; Virulence Factors; Virulence; Anti-Bacterial Agents; Gram-Positive Bacterial Infections
PubMed: 37811975
DOI: 10.1128/spectrum.00201-23 -
BMC Genomics May 2024Fusarium zanthoxyli is a destructive pathogen causing stem canker in prickly ash, an ecologically and economically important forest tree. However, the genome lack of F....
BACKGROUND
Fusarium zanthoxyli is a destructive pathogen causing stem canker in prickly ash, an ecologically and economically important forest tree. However, the genome lack of F. zanthoxyli has hindered research on its interaction with prickly ash and the development of precise control strategies for stem canker.
RESULTS
In this study, we sequenced and annotated a relatively high-quality genome of F. zanthoxyli with a size of 43.39 Mb, encoding 11,316 putative genes. Pathogenicity-related factors are predicted, comprising 495 CAZymes, 217 effectors, 156 CYP450s, and 202 enzymes associated with secondary metabolism. Besides, a comparative genomics analysis revealed Fusarium and Colletotrichum diverged from a shared ancestor approximately 141.1 ~ 88.4 million years ago (MYA). Additionally, a phylogenomic investigation of 12 different phytopathogens within Fusarium indicated that F. zanthoxyli originated approximately 34.6 ~ 26.9 MYA, and events of gene expansion and contraction within them were also unveiled. Finally, utilizing conserved domain prediction, the results revealed that among the 59 unique genes, the most enriched domains were PnbA and ULP1. Among the 783 expanded genes, the most enriched domains were PKc_like kinases and those belonging to the APH_ChoK_Like family.
CONCLUSION
This study sheds light on the genetic basis of F. zanthoxyli's pathogenicity and evolution which provides valuable information for future research on its molecular interactions with prickly ash and the development of effective strategies to combat stem canker.
Topics: Fusarium; Phylogeny; Genomics; Plant Diseases; Evolution, Molecular; Genome, Fungal; Virulence
PubMed: 38773367
DOI: 10.1186/s12864-024-10424-w -
ACS Infectious Diseases Jan 2020Natural products from microorganisms are important small molecules that play roles in various biological processes like cellular growth, motility, nutrient acquisition,... (Review)
Review
Natural products from microorganisms are important small molecules that play roles in various biological processes like cellular growth, motility, nutrient acquisition, stress response, biofilm formation, and defense. It is hypothesized that pathogens exploit these molecules to regulate virulence and persistence during infections. Here, we present selected examples of signaling natural products from human pathogenic bacteria that use these metabolites to gain a competitive advantage. Targeting these signaling systems provides novel strategies to antimicrobial treatments.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Biological Products; Host Microbial Interactions; Humans; Secondary Metabolism; Signal Transduction; Virulence
PubMed: 31617342
DOI: 10.1021/acsinfecdis.9b00286