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Annual Review of Microbiology Sep 2022is a globally distributed, lethal pathogen of humans. The virulence armamentarium of appears to have been developed on a scaffold of antiphagocytic defenses found... (Review)
Review
is a globally distributed, lethal pathogen of humans. The virulence armamentarium of appears to have been developed on a scaffold of antiphagocytic defenses found among diverse, mostly free-living species of . Pathoadaptation was further aided by the modularity, flexibility, and interactivity characterizing mycobacterial effectors and their regulators. During emergence of , novel genetic material was acquired, created, and integrated with existing tools. The major mutational mechanisms underlying these adaptations are discussed in this review, with examples. During its evolution, lost the ability and/or opportunity to engage in lateral gene transfer, but despite this it has retained the adaptability that characterizes mycobacteria. exemplifies the evolutionary genomic mechanisms underlying adoption of the pathogenic niche, and studies of its evolution have uncovered a rich array of discoveries about how new pathogens are made.
Topics: Evolution, Molecular; Gene Transfer, Horizontal; Humans; Mycobacterium tuberculosis; Tuberculosis; Virulence; Virulence Factors
PubMed: 35709500
DOI: 10.1146/annurev-micro-121321-093031 -
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 -
Nature Reviews. Microbiology Aug 2020Xanthomonas spp. encompass a wide range of plant pathogens that use numerous virulence factors for pathogenicity and fitness in plant hosts. In this Review, we examine... (Review)
Review
Xanthomonas spp. encompass a wide range of plant pathogens that use numerous virulence factors for pathogenicity and fitness in plant hosts. In this Review, we examine recent insights into host-pathogen co-evolution, diversity in Xanthomonas populations and host specificity of Xanthomonas spp. that have substantially improved our fundamental understanding of pathogen biology. We emphasize the virulence factors in xanthomonads, such as type III secreted effectors including transcription activator-like effectors, type II secretion systems, diversity resulting in host specificity, evolution of emerging strains, activation of susceptibility genes and strategies of host evasion. We summarize the genomic diversity in several Xanthomonas spp. and implications for disease outbreaks, management strategies and breeding for disease resistance.
Topics: Host-Pathogen Interactions; Plant Diseases; Plants; Virulence; Virulence Factors; Xanthomonas
PubMed: 32346148
DOI: 10.1038/s41579-020-0361-8 -
International Journal of Molecular... Aug 2021The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation... (Review)
Review
The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation of bacterial growth and pathogenicity. Accumulating data indicate that tRNA post-transcriptional modifications possess a central role in both the formation of bacterial cell wall and the modulation of transcription and translation fidelity, but also in the expression of virulence factors. Evolutionary conserved modifications in tRNA nucleosides ensure the proper folding and stability redounding to a totally functional molecule. However, environmental factors including stress conditions can cause various alterations in tRNA modifications, disturbing the pathogen homeostasis. Post-transcriptional modifications adjacent to the anticodon stem-loop, for instance, have been tightly linked to bacterial infectivity. Currently, advances in high throughput methodologies have facilitated the identification and functional investigation of such tRNA modifications offering a broader pool of putative alternative molecular targets and therapeutic avenues against bacterial infections. Herein, we focus on tRNA epitranscriptome shaping regarding modifications with a key role in bacterial infectivity including opportunistic pathogens of the human microbiome.
Topics: Anticodon; Bacteria; Humans; Nucleosides; Protein Biosynthesis; RNA Processing, Post-Transcriptional; RNA, Transfer; Transcriptome; Virulence
PubMed: 34445114
DOI: 10.3390/ijms22168409 -
Annual Review of Microbiology Sep 2023Bacteria are single-celled organisms that carry a comparatively small set of genetic information, typically consisting of a few thousand genes that can be selectively... (Review)
Review
Bacteria are single-celled organisms that carry a comparatively small set of genetic information, typically consisting of a few thousand genes that can be selectively activated or repressed in an energy-efficient manner and transcribed to encode various biological functions in accordance with environmental changes. Research over the last few decades has uncovered various ingenious molecular mechanisms that allow bacterial pathogens to sense and respond to different environmental cues or signals to activate or suppress the expression of specific genes in order to suppress host defenses and establish infections. In the setting of infection, pathogenic bacteria have evolved various intelligent mechanisms to reprogram their virulence to adapt to environmental changes and maintain a dominant advantage over host and microbial competitors in new niches. This review summarizes the bacterial virulence programming mechanisms that enable pathogens to switch from acute to chronic infection, from local to systemic infection, and from infection to colonization. It also discusses the implications of these findings for the development of new strategies to combat bacterial infections.
Topics: Virulence; Bacteria
PubMed: 37406345
DOI: 10.1146/annurev-micro-032521-025954 -
Nature Microbiology May 2022Fungal pathogens cause more than a billion human infections every year, resulting in more than 1.6 million deaths annually. Understanding the natural history and... (Review)
Review
Fungal pathogens cause more than a billion human infections every year, resulting in more than 1.6 million deaths annually. Understanding the natural history and evolutionary ecology of fungi is helping us understand how disease-relevant traits have repeatedly evolved. Different types and mechanisms of genetic variation have contributed to the evolution of fungal pathogenicity and specific genetic differences distinguish pathogens from non-pathogens. Insights into the traits, genetic elements, and genetic and ecological mechanisms that contribute to the evolution of fungal pathogenicity are crucial for developing strategies to both predict emergence of fungal pathogens and develop drugs to combat them.
Topics: Fungi; Humans; Life Style; Virulence
PubMed: 35508719
DOI: 10.1038/s41564-022-01112-0 -
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 -
Advances in Experimental Medicine and... 2020Calcium (Ca) is a universal signaling ion, whose major informational role shaped the evolution of signaling pathways, enabling cellular communications and responsiveness... (Review)
Review
Calcium (Ca) is a universal signaling ion, whose major informational role shaped the evolution of signaling pathways, enabling cellular communications and responsiveness to both the intracellular and extracellular environments. Elaborate Ca regulatory networks have been well characterized in eukaryotic cells, where Ca regulates a number of essential cellular processes, ranging from cell division, transport and motility, to apoptosis and pathogenesis. However, in bacteria, the knowledge on Ca signaling is still fragmentary. This is complicated by the large variability of environments that bacteria inhabit with diverse levels of Ca. Yet another complication arises when bacterial pathogens invade a host and become exposed to different levels of Ca that (1) are tightly regulated by the host, (2) control host defenses including immune responses to bacterial infections, and (3) become impaired during diseases. The invading pathogens evolved to recognize and respond to the host Ca, triggering the molecular mechanisms of adhesion, biofilm formation, host cellular damage, and host-defense resistance, processes enabling the development of persistent infections. In this review, we discuss: (1) Ca as a determinant of a host environment for invading bacterial pathogens, (2) the role of Ca in regulating main events of host colonization and bacterial virulence, and (3) the molecular mechanisms of Ca signaling in bacterial pathogens.
Topics: Bacteria; Bacterial Infections; Calcium; Host Microbial Interactions; Humans; Virulence
PubMed: 31646536
DOI: 10.1007/978-3-030-12457-1_33 -
Current Opinion in Microbiology Dec 2019Extracellular vesicles play a significant role in many aspects of cellular life including cell-to-cell communication, pathogenesis and cancer progression. However very... (Review)
Review
Extracellular vesicles play a significant role in many aspects of cellular life including cell-to-cell communication, pathogenesis and cancer progression. However very little is known about their role in fungi and we are just at the beginning of understanding their influence on fungal pathophysiology and host-pathogen interactions. Recent findings have revealed a role for fungal vesicles in triggering anti-microbial activities as well as in modulating virulence strategies, suggesting potential new avenues for antifungal therapies. In this review, we summarize our current understanding of fungal extracellular vesicles, including their biogenesis, secretion and size variation, and discuss how they may influence the human immune response and some key questions that remain unanswered.
Topics: Cell Communication; Extracellular Vesicles; Fungal Proteins; Fungi; Host-Pathogen Interactions; Humans; Organelle Biogenesis; Virulence
PubMed: 31280026
DOI: 10.1016/j.mib.2019.05.007 -
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