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FEMS Microbiology Reviews Jan 2020Xanthomonas is a well-studied genus of bacterial plant pathogens whose members cause a variety of diseases in economically important crops worldwide. Genomic and... (Review)
Review
Xanthomonas is a well-studied genus of bacterial plant pathogens whose members cause a variety of diseases in economically important crops worldwide. Genomic and functional studies of these phytopathogens have provided significant understanding of microbial-host interactions, bacterial virulence and host adaptation mechanisms including microbial ecology and epidemiology. In addition, several strains of Xanthomonas are important as producers of the extracellular polysaccharide, xanthan, used in the food and pharmaceutical industries. This polymer has also been implicated in several phases of the bacterial disease cycle. In this review, we summarise the current knowledge on the infection strategies and regulatory networks controlling virulence and adaptation mechanisms from Xanthomonas species and discuss the novel opportunities that this body of work has provided for disease control and plant health.
Topics: Adaptation, Physiological; Genome, Bacterial; Host-Pathogen Interactions; Plant Diseases; Plants; Virulence; Xanthomonas
PubMed: 31578554
DOI: 10.1093/femsre/fuz024 -
EBioMedicine Feb 2023Novel therapeutics to manage bacterial infections are urgently needed as the impact and prevalence of antimicrobial resistance (AMR) grows. Antivirulence therapeutics... (Review)
Review
Novel therapeutics to manage bacterial infections are urgently needed as the impact and prevalence of antimicrobial resistance (AMR) grows. Antivirulence therapeutics are an alternative approach to antibiotics that aim to attenuate virulence rather than target bacterial essential functions, while minimizing microbiota perturbation and the risk of AMR development. Beyond known virulence factors, pathogen-associated genes (PAGs; genes found only in pathogens to date) may play an important role in virulence or host association. Many identified PAGs encode uncharacterized hypothetical proteins and represent an untapped wealth of novel drug targets. Here, we review current advances in antivirulence drug research and development, including PAG identification, and provide a comprehensive workflow from the discovery of antivirulence drug targets to drug discovery. We highlight the importance of integrating bioinformatic/genomic-based methods for novel virulence factor discovery, coupled with experimental characterization, into existing drug screening platforms to develop novel and effective antivirulence drugs.
Topics: Humans; Workflow; Anti-Bacterial Agents; Virulence; Virulence Factors; Genetic Association Studies
PubMed: 36628845
DOI: 10.1016/j.ebiom.2022.104429 -
Molecular Microbiology Jul 2019Rhodococcus equi is the only recognized animal pathogenic species within an extended genus of metabolically versatile Actinobacteria of considerable biotechnological... (Review)
Review
Rhodococcus equi is the only recognized animal pathogenic species within an extended genus of metabolically versatile Actinobacteria of considerable biotechnological interest. Best known as a horse pathogen, R. equi is commonly isolated from other animal species, particularly pigs and ruminants, and causes severe opportunistic infections in people. As typical in the rhodococci, R. equi niche specialization is extrachromosomally determined, via a conjugative virulence plasmid that promotes intramacrophage survival. Progress in the molecular understanding of R. equi and its recent rise as a novel paradigm of multihost adaptation has been accompanied by an unusual nomenclatural instability, with a confusing succession of names: "Prescottia equi", "Prescotella equi", Corynebacterium hoagii and Rhodococcus hoagii. This article reviews current advances in the genomics, biology and virulence of this pathogenic actinobacterium with a unique mechanism of plasmid-transferable animal host tropism. It also discusses the taxonomic and nomenclatural issues around R. equi in the light of recent phylogenomic evidence that confirms its membership as a bona fide Rhodococcus.
Topics: Actinomycetales Infections; Animals; Genomics; Horses; Phylogeny; Plasmids; Rhodococcus; Rhodococcus equi; Swine; Virulence
PubMed: 31099908
DOI: 10.1111/mmi.14267 -
JCI Insight Jul 2023The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells....
The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major-infected (L. major-infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner.
Topics: Leishmania major; Phagocytes; Apoptosis; Humans; Virulence; Mice, Inbred C57BL; Cells, Cultured; Mice; Animals
PubMed: 37310793
DOI: 10.1172/jci.insight.169020 -
FEMS Yeast Research Jun 2021Candida albicans typically resides in the human gastrointestinal tract and mucosal membranes as a commensal organism. To adapt and cope with the host immune system, it... (Review)
Review
Candida albicans typically resides in the human gastrointestinal tract and mucosal membranes as a commensal organism. To adapt and cope with the host immune system, it has evolved a variety of mechanisms of adaptation such as stress-induced mutagenesis and epigenetic regulation. Niche-specific patterns of gene expression also allow the fungus to fine-tune its response to specific microenvironments in the host and switch from harmless commensal to invasive pathogen. Proteome plasticity produced by CUG ambiguity, on the other hand is emerging as a new layer of complexity in C. albicans adaptation, pathogenesis, and drug resistance. Such proteome plasticity is the result of a genetic code alteration where the leucine CUG codon is translated mainly as serine (97%), but maintains some level of leucine (3%) assignment. In this review, we dissect the link between C. albicans non-standard CUG translation, proteome plasticity, host adaptation and pathogenesis. We discuss published work showing how this pathogen uses the fidelity of protein synthesis to spawn novel virulence traits.
Topics: Adaptation, Physiological; Candida albicans; Codon; Drug Resistance, Fungal; Epigenesis, Genetic; Protein Biosynthesis; Proteome; Virulence
PubMed: 34021562
DOI: 10.1093/femsyr/foab032 -
International Journal of Molecular... Jan 2022Preterm infants are at increased risk for invasive neonatal bacterial infections. , a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis,... (Review)
Review
Preterm infants are at increased risk for invasive neonatal bacterial infections. , a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of as a cause of neonatal morbidity and mortality.
Topics: Age Factors; Bacterial Toxins; Biofilms; Disease Susceptibility; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunity, Innate; Infant, Newborn; Neonatal Sepsis; Risk Factors; Staphylococcal Infections; Staphylococcus epidermidis; Virulence; Virulence Factors
PubMed: 35055041
DOI: 10.3390/ijms23020860 -
Molecular Plant-microbe Interactions :... Apr 2023Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles that deliver bioactive proteins, nucleic acids, lipids, and other small molecules from donor to... (Review)
Review
Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles that deliver bioactive proteins, nucleic acids, lipids, and other small molecules from donor to recipient cells. They have attracted significant interest recently due to their important roles in regulating plant-microbe interaction. During microbial infection, plant EVs play a prominent role in defense by delivering small regulatory RNA into pathogens, resulting in the silencing of pathogen virulence genes. Pathogens also deliver small RNAs into plant cells to silence host immunity genes. Recent evidence indicates that microbial EVs may be involved in pathogenesis and host immunity modulation by transporting RNAs and other biomolecules. However, the biogenesis and function of microbial EVs in plant-microbe interaction remain ill-defined. In this review, we discuss various aspects of microbial EVs, with a particular focus on current methods for EV isolation, composition, biogenesis, and their roles in plant-microbe interaction. We also discussed the potential role of microbial EVs in cross-kingdom RNA trafficking from pathogens to plants, as it is a highly likely possibility to explore in the future. [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: RNA; Extracellular Vesicles; RNA Interference; Biological Transport; Virulence
PubMed: 36574017
DOI: 10.1094/MPMI-08-22-0162-FI -
Frontiers in Cellular and Infection... 2022Many bacterial species, including several pathogens, can enter a so-called "viable but non-culturable" (VBNC) state when subjected to stress. Bacteria in the VBNC state... (Review)
Review
Many bacterial species, including several pathogens, can enter a so-called "viable but non-culturable" (VBNC) state when subjected to stress. Bacteria in the VBNC state are metabolically active but have lost their ability to grow on standard culture media, which compromises their detection by conventional techniques based on bacterial division. Under certain conditions, VBNC bacteria can regain their growth capacity and, for pathogens, their virulence potential, through a process called resuscitation. Here, we review the current state of knowledge of the VBNC state of (), a Gram-positive pathogenic bacterium responsible for listeriosis, one of the most dangerous foodborne zoonosis. After a brief summary of characteristics of VBNC bacteria, we highlight work on VBNC in the environment and in agricultural and food industry settings, with particular emphasis on the impact of antimicrobial treatments. We subsequently discuss recent data suggesting that can enter the VBNC state in the host, raising the possibility that VBNC forms contribute to the asymptomatic carriage of this pathogen in wildlife, livestock and even humans. We also consider the resuscitation and virulence potential of VBNC and the danger posed by these bacteria to at-risk individuals, particularly pregnant women. Overall, we put forth the hypothesis that VBNC forms contribute to adaptation, persistence, and transmission of between different ecological niches in the One-Health , and suggest that screening for healthy carriers, using alternative techniques to culture-based enrichment methods, should better prevent listeriosis risks.
Topics: Animals; Female; Humans; Listeria monocytogenes; Listeriosis; One Health; Pregnancy; Virulence; Zoonoses
PubMed: 35372114
DOI: 10.3389/fcimb.2022.849915 -
Frontiers in Cellular and Infection... 2023
Topics: Fungi; Virulence; Plants
PubMed: 37065206
DOI: 10.3389/fcimb.2023.1168148 -
Virulence Dec 2021Mycoplasmas, the smallest bacteria lacking a cell wall, can cause various diseases in both humans and animals. Mycoplasmas harbor a variety of virulence factors that... (Review)
Review
Mycoplasmas, the smallest bacteria lacking a cell wall, can cause various diseases in both humans and animals. Mycoplasmas harbor a variety of virulence factors that enable them to overcome numerous barriers of entry into the host; using accessory proteins, mycoplasma adhesins can bind to the receptors or extracellular matrix of the host cell. Although the host immune system can eradicate the invading mycoplasma in most cases, a few sagacious mycoplasmas employ a series of invasion and immune escape strategies to ensure their continued survival within their hosts. For instance, capsular polysaccharides are crucial for anti-phagocytosis and immunomodulation. Invasive enzymes degrade reactive oxygen species, neutrophil extracellular traps, and immunoglobulins. Biofilm formation is important for establishing a persistent infection. During proliferation, successfully surviving mycoplasmas generate numerous metabolites, including hydrogen peroxide, ammonia and hydrogen sulfide; or secrete various exotoxins, such as community-acquired respiratory distress syndrome toxin, and hemolysins; and express various pathogenic enzymes, all of which have potent toxic effects on host cells. Furthermore, some inherent components of mycoplasmas, such as lipids, membrane lipoproteins, and even mycoplasma-generated superantigens, can exert a significant pathogenic impact on the host cells or the immune system. In this review, we describe the proposed virulence factors in the toolkit of notorious mycoplasmas to better understand the pathogenic features of these bacteria, along with their pathogenic mechanisms.
Topics: Animals; Biofilms; Host-Pathogen Interactions; Humans; Mice; Mycoplasma; Phagocytosis; Virulence; Virulence Factors
PubMed: 33704021
DOI: 10.1080/21505594.2021.1889813