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Toxins Sep 2021is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. has a high level of... (Review)
Review
is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant (CA-MRSA), combined with the important severity of infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant continues to be a major health concern, necessitating the development of novel therapeutic strategies. uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.
Topics: Anti-Bacterial Agents; Staphylococcus aureus; Toxins, Biological; Virulence; Virulence Factors
PubMed: 34678970
DOI: 10.3390/toxins13100677 -
Infection, Genetics and Evolution :... Apr 2021Cryptococcus neoformans is a dimorphic fungus that causes lethal meningoencephalitis mainly in immunocompromised individuals. Different morphotypes enable this... (Review)
Review
Cryptococcus neoformans is a dimorphic fungus that causes lethal meningoencephalitis mainly in immunocompromised individuals. Different morphotypes enable this environmental fungus and opportunistic pathogen to adapt to different natural niches and exhibit different levels of pathogenicity in various hosts. It is well-recognized that C. neoformans undergoes bisexual or unisexual reproduction in vitro to generate genotypic, morphotypic, and phenotypic diversity, which augments its ability for adaptation. However, if and how sexual reproduction and the meiotic machinery exert any direct impact on the infection process is unclear. This review summarizes recent discoveries on the regulation of cryptococcal life cycle and morphogenesis, and how they impact cryptococcal pathogenicity. The potential role of the meiotic machinery on ploidy regulation during cryptococcal infection is also discussed. This review aims to stimulate further investigation on links between fungal morphogenesis, sexual reproduction, and virulence.
Topics: Cryptococcus neoformans; Humans; Morphogenesis; Reproduction; Virulence
PubMed: 33497839
DOI: 10.1016/j.meegid.2021.104731 -
Microbiology and Molecular Biology... Nov 2019is a highly versatile pathogen capable of causing infections in a wide range of domestic and wild animals as well as in humans and nonhuman primates. Despite over... (Review)
Review
is a highly versatile pathogen capable of causing infections in a wide range of domestic and wild animals as well as in humans and nonhuman primates. Despite over 135 years of research, the molecular basis for the myriad manifestations of pathogenesis and the determinants of phylogeny remain poorly defined. The current availability of multiple genome sequences now makes it possible to delve into the underlying genetic mechanisms of fitness and virulence. Using whole-genome sequences, the genotypes, including the capsular genotypes, lipopolysaccharide (LPS) genotypes, and multilocus sequence types, as well as virulence factor-encoding genes of isolates from different clinical presentations can be characterized rapidly and accurately. Putative genetic factors that contribute to virulence, fitness, host specificity, and disease predilection can also be identified through comparative genome analysis of different isolates. However, although some knowledge about genotypes, fitness, and pathogenesis has been gained from the recent whole-genome sequencing and comparative analysis studies of , there is still a long way to go before we fully understand the pathogenic mechanisms of this important zoonotic pathogen. The quality of several available genome sequences is low, as they are assemblies with relatively low coverage, and genomes of isolates from some uncommon host species are still limited or lacking. Here, we review recent advances, as well as continuing knowledge gaps, in our understanding of determinants contributing to virulence, fitness, host specificity, disease predilection, and phylogeny of .
Topics: Animals; Genetic Variation; Genome, Bacterial; Genomics; Genotype; Host Specificity; Humans; Pasteurella Infections; Pasteurella multocida; Phylogeny; Virulence; Virulence Factors
PubMed: 31484691
DOI: 10.1128/MMBR.00014-19 -
International Journal of Molecular... Jul 2020Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause...
Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...].
Topics: Bacteria; Humans; Virulence; Virulence Factors
PubMed: 32727013
DOI: 10.3390/ijms21155320 -
Science (New York, N.Y.) Jun 2018Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit...
Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit their virulence. Although sRNA trafficking has been observed in a wide variety of interactions, how sRNAs are transferred, especially from hosts to pathogens and pests, is still unknown. Here, we show that host cells secrete exosome-like extracellular vesicles to deliver sRNAs into fungal pathogen These sRNA-containing vesicles accumulate at the infection sites and are taken up by the fungal cells. Transferred host sRNAs induce silencing of fungal genes critical for pathogenicity. Thus, has adapted exosome-mediated cross-kingdom RNA interference as part of its immune responses during the evolutionary arms race with the pathogen.
Topics: Arabidopsis; Botrytis; Extracellular Vesicles; Host-Pathogen Interactions; Plant Diseases; Plant Immunity; RNA Interference; RNA, Plant; RNA, Small Interfering; Virulence; Virulence Factors
PubMed: 29773668
DOI: 10.1126/science.aar4142 -
Virulence Dec 2020Trehalose is a disaccharide of two D-glucose molecules linked by a glycosidic linkage, which plays both structural and functional roles in bacteria. Trehalose can be... (Review)
Review
Trehalose is a disaccharide of two D-glucose molecules linked by a glycosidic linkage, which plays both structural and functional roles in bacteria. Trehalose can be synthesized and degraded by several pathways, and induction of trehalose biosynthesis is typically associated with exposure to abiotic stress. The ability of trehalose to protect against abiotic stress has been exploited to stabilize a range of bacterial vaccines. More recently, there has been interest in the role of this molecule in microbial virulence. There is now evidence that trehalose or trehalose derivatives play important roles in virulence of a diverse range of Gram-positive and Gram-negative pathogens of animals or plants. Trehalose and/or trehalose derivatives can play important roles in host colonization and growth in the host, and can modulate the interactions with host defense mechanisms. However, the roles are typically pathogen-specific. These findings suggest that trehalose metabolism may be a target for novel pathogen-specific rather than broad spectrum interventions.
Topics: Animals; Bacteria; Bacterial Infections; Host-Pathogen Interactions; Humans; Plants; Stress, Physiological; Trehalose; Virulence
PubMed: 32862781
DOI: 10.1080/21505594.2020.1809326 -
Virulence Dec 2024The genus includes human, animal, insect, and plant pathogens as well as many symbionts and harmless bacteria. Within this genus are and the complex, with four human... (Review)
Review
The genus includes human, animal, insect, and plant pathogens as well as many symbionts and harmless bacteria. Within this genus are and the complex, with four human pathogenic species that are highly related at the genomic level including the causative agent of plague, . Extensive laboratory, field work, and clinical research have been conducted to understand the underlying pathogenesis and zoonotic transmission of these pathogens. There are presently more than 500 whole genome sequences from which an evolutionary footprint can be developed that details shared and unique virulence properties. Whereas the virulence of now seems in apparent homoeostasis within its flea transmission cycle, substantial evolutionary changes that affect transmission and disease severity continue to ndergo apparent selective pressure within the other that cause intestinal diseases. In this review, we will summarize the present understanding of the virulence and pathogenesis of , highlighting shared mechanisms of virulence and the differences that determine the infection niche and disease severity.
Topics: Animals; Humans; Yersinia; Virulence; Yersinia pestis; Plague; Yersinia Infections
PubMed: 38389313
DOI: 10.1080/21505594.2024.2316439 -
Proceedings of the National Academy of... Apr 2022Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the...
Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the application of machine learning (ML) to whole-genome sequences (WGSs) has facilitated pathogen identification. However, relying solely on genetic information to identify emerging or new pathogens is fundamentally constrained, especially if novel virulence factors exist. In addition, even WGSs with ML pipelines are unable to discern phenotypes associated with cryptic genetic loci linked to virulence. Here, we set out to determine if ML using phenotypic hallmarks of pathogenesis could assess potential pathogenic threat without using any sequence-based analysis. This approach successfully classified potential pathogenetic threat associated with previously machine-observed and unobserved bacteria with 99% and 85% accuracy, respectively. This work establishes a phenotype-based pipeline for potential pathogenic threat assessment, which we term PathEngine, and offers strategies for the identification of bacterial pathogens.
Topics: Bacteria; Genome, Bacterial; Machine Learning; Phenotype; Virulence; Virulence Factors; Whole Genome Sequencing
PubMed: 35363569
DOI: 10.1073/pnas.2112886119 -
Nature Microbiology Jan 2020Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors,... (Review)
Review
Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors, such as secreted toxins and effector proteins, to manipulate host cellular processes and establish a replicative niche. Survival of eukaryotic organisms in the face of such challenge requires host mechanisms to detect and counteract these pathogen-specific virulence strategies. In this Review, we focus on effector-triggered immunity (ETI) in metazoan organisms as a mechanism for pathogen sensing and distinguishing pathogenic from non-pathogenic microorganisms. For the purposes of this Review, we adopt the concept of ETI formulated originally in the context of plant pathogens and their hosts, wherein specific host proteins 'guard' central cellular processes and trigger inflammatory responses following pathogen-driven disruption of these processes. While molecular mechanisms of ETI are well-described in plants, our understanding of functionally analogous mechanisms in metazoans is still emerging. In this Review, we present an overview of ETI in metazoans and discuss recently described cellular processes that are guarded by the host. Although all pathogens manipulate host pathways, we focus primarily on bacterial pathogens and highlight pathways of effector-triggered immune defence that sense disruption of core cellular processes by pathogens. Finally, we discuss recent developments in our understanding of how pathogens can evade ETI to overcome these host adaptations.
Topics: Animals; Bacteria; Bacterial Infections; Immune Evasion; Immunity, Innate; Inflammasomes; Receptors, Pattern Recognition; Signal Transduction; Virulence; Virulence Factors
PubMed: 31857733
DOI: 10.1038/s41564-019-0623-2 -
FEMS Microbiology Reviews Jan 2018Metals are essential for life, and they play a central role in the struggle between infecting microbes and their hosts. In fact, an important aspect of microbial... (Review)
Review
Metals are essential for life, and they play a central role in the struggle between infecting microbes and their hosts. In fact, an important aspect of microbial pathogenesis is the 'nutritional immunity', in which metals are actively restricted (or, in an extended definition of the term, locally enriched) by the host to hinder microbial growth and virulence. Consequently, fungi have evolved often complex regulatory networks, uptake and detoxification systems for essential metals such as iron, zinc, copper, nickel and manganese. These systems often differ fundamentally from their bacterial counterparts, but even within the fungal pathogens we can find common and unique solutions to maintain metal homeostasis. Thus, we here compare the common and species-specific mechanisms used for different metals among different fungal species-focusing on important human pathogens such as Candida albicans, Aspergillus fumigatus or Cryptococcus neoformans, but also looking at model fungi such as Saccharomyces cerevisiae or A. nidulans as well-studied examples for the underlying principles. These direct comparisons of our current knowledge reveal that we have a good understanding how model fungal pathogens take up iron or zinc, but that much is still to learn about other metals and specific adaptations of individual species-not the least to exploit this knowledge for new antifungal strategies.
Topics: Fungi; Homeostasis; Metals; Virulence
PubMed: 29069482
DOI: 10.1093/femsre/fux050