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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 -
Biochemical Society Transactions Nov 2021Despite being considered the simplest form of life, bacteria remain enigmatic, particularly in light of pathogenesis and evolving antimicrobial resistance. After three... (Review)
Review
Despite being considered the simplest form of life, bacteria remain enigmatic, particularly in light of pathogenesis and evolving antimicrobial resistance. After three decades of genomics, we remain some way from understanding these organisms, and a substantial proportion of genes remain functionally unknown. Methodological advances, principally mass spectrometry (MS), are paving the way for parallel analysis of the proteome, metabolome and lipidome. Each provides a global, complementary assay, in addition to genomics, and the ability to better comprehend how pathogens respond to changes in their internal (e.g. mutation) and external environments consistent with infection-like conditions. Such responses include accessing necessary nutrients for survival in a hostile environment where co-colonizing bacteria and normal flora are acclimated to the prevailing conditions. Multi-omics can be harnessed across temporal and spatial (sub-cellular) dimensions to understand adaptation at the molecular level. Gene deletion libraries, in conjunction with large-scale approaches and evolving bioinformatics integration, will greatly facilitate next-generation vaccines and antimicrobial interventions by highlighting novel targets and pathogen-specific pathways. MS is also central in phenotypic characterization of surface biomolecules such as lipid A, as well as aiding in the determination of protein interactions and complexes. There is increasing evidence that bacteria are capable of widespread post-translational modification, including phosphorylation, glycosylation and acetylation; with each contributing to virulence. This review focuses on the bacterial genotype to phenotype transition and surveys the recent literature showing how the genome can be validated at the proteome, metabolome and lipidome levels to provide an integrated view of organism response to host conditions.
Topics: Adaptation, Physiological; Bacteria; Genotype; Host-Pathogen Interactions; Lipidomics; Mass Spectrometry; Metabolome; Phenotype; Protein Processing, Post-Translational; Proteome; Virulence
PubMed: 34374408
DOI: 10.1042/BST20191088 -
Molecular Aspects of Medicine Oct 2021Host-pathogen interactions at the molecular level are the key to fungal pathogenesis. Fungal pathogens utilize several mechanisms such as adhesion, invasion, phenotype... (Review)
Review
Host-pathogen interactions at the molecular level are the key to fungal pathogenesis. Fungal pathogens utilize several mechanisms such as adhesion, invasion, phenotype switching and metabolic adaptations, to survive in the host environment and respond. Post-transcriptional and translational regulations have emerged as key regulatory mechanisms ensuring the virulence and survival of fungal pathogens. Through these regulations, fungal pathogens effectively alter their protein pool, respond to various stress, and undergo morphogenesis, leading to efficient and comprehensive changes in fungal physiology. The regulation of virulence through post-transcriptional and translational regulatory mechanisms is mediated through mRNA elements (cis factors) or effector molecules (trans factors). The untranslated regions upstream and downstream of the mRNA, as well as various RNA-binding proteins involved in translation initiation or circularization of the mRNA, play pivotal roles in the regulation of morphology and virulence by influencing protein synthesis, protein isoforms, and mRNA stability. Therefore, post-transcriptional and translational mechanisms regulating the morphology, virulence and drug-resistance processes in fungal pathogens can be the target for new therapeutics. With improved "omics" technologies, these regulatory mechanisms are increasingly coming to the forefront of basic biology and drug discovery. This review aims to discuss various modes of post-transcriptional and translation regulations, and how these mechanisms exert influence in the virulence and morphogenesis of fungal pathogens.
Topics: Adaptation, Physiological; Gene Expression Regulation, Fungal; Humans; Protein Biosynthesis; Protein Processing, Post-Translational; Virulence
PubMed: 34497025
DOI: 10.1016/j.mam.2021.101017 -
Journal of Molecular Biology Nov 2019Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course... (Review)
Review
Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course of an infection, subpopulations occur, which differ in certain virulence-relevant factors, stress adaptation functions or physiological and metabolic abilities. The mechanisms driving this heterogeneity are divergent reactions of the pathogens to differences in host tissue microenvironments. In addition, certain genetic regulatory circuits with positive feedback loops and stochastic differences in gene expression can generate endogenous fluctuations in regulatory components leading to bistable expression of virulence-associated functions. Here, we focus on the occurrence of phenotypic heterogeneity in populations of well-studied examples of pathogens, which enables cooperative, social behavior where a subpopulation of producers shares fitness- and/or virulence-relevant goods and traits with non-producers. We further highlight that this strategy allows preadaptation of a subgroup of cells to recurrent and thus predictable changes of the environment that they encounter during the different stages of the infection. The diversity within bacterial communities has a significant influence on the survival of the pathogens within their hosts and the progression of the disease.
Topics: Adaptation, Physiological; Bacteria; Bacterial Physiological Phenomena; Biological Variation, Population; Host-Pathogen Interactions; Microbiological Phenomena; Nitric Oxide; Oxidation-Reduction; Phenotype; Reactive Oxygen Species; Stress, Physiological; Type III Secretion Systems; Virulence; Virulence Factors
PubMed: 31260693
DOI: 10.1016/j.jmb.2019.06.024 -
Microbiological Research Dec 2023Fusarium spp. comprise various species of filamentous fungi that cause severe diseases in plant crops of both agricultural and forestry interest. These plant pathogens... (Review)
Review
Fusarium spp. comprise various species of filamentous fungi that cause severe diseases in plant crops of both agricultural and forestry interest. These plant pathogens produce a wide range of molecules with diverse chemical structures and biological activities. Genetic functional analyses of some of these compounds have shown their role as virulence factors (VF). However, their mode of action and contributions to the infection process for many of these molecules are still unknown. This review aims to analyze the state of the art in Fusarium VF, emphasizing their biological targets on the plant hosts. It also addresses the current experimental approaches to improve our understanding of their role in virulence and suggests relevant research questions that remain to be answered with a greater focus on species of agroeconomic importance. In this review, a total of 37 confirmed VF are described, including 22 proteinaceous and 15 non-proteinaceous molecules, mainly from Fusarium oxysporum and Fusarium graminearum and, to a lesser extent, in Fusarium verticillioides and Fusarium solani.
Topics: Virulence Factors; Fusarium; Virulence; Crops, Agricultural; Plant Diseases
PubMed: 37783182
DOI: 10.1016/j.micres.2023.127506 -
Fungal Biology May 2023The Botryosphaeriaceae family comprises numerous fungal pathogens capable of causing economically meaningful diseases in a wide range of crops. Many of its members can...
The Botryosphaeriaceae family comprises numerous fungal pathogens capable of causing economically meaningful diseases in a wide range of crops. Many of its members can live as endophytes and turn into aggressive pathogens following the onset of environmental stress events. Their ability to cause disease may rely on the production of a broad set of effectors, such as cell wall-degrading enzymes, secondary metabolites, and peptidases. Here, we conducted comparative analyses of 41 genomes representing six Botryosphaeriaceae genera to provide insights into the genetic features linked to pathogenicity and virulence. We show that these Botryosphaeriaceae genomes possess a large diversity of carbohydrate-active enzymes (CAZymes; 128 families) and peptidases (45 families). Botryosphaeria, Neofusicoccum, and Lasiodiplodia presented the highest number of genes encoding CAZymes involved in the degradation of the plant cell wall components. The genus Botryosphaeria also exhibited the highest abundance of secreted CAZymes and peptidases. Generally, the secondary metabolites gene cluster profile was consistent in the Botryosphaeriaceae family, except for Diplodia and Neoscytalidium. At the strain level, Neofusicoccum parvum NpBt67 stood out among all the Botryosphaeriaceae genomes, presenting a higher number of secretome constituents. In contrast, the Diplodia strains showed the lowest richness of the pathogenicity- and virulence-related genes, which may correlate with their low virulence reported in previous studies. Overall, these results contribute to a better understanding of the mechanisms underlying pathogenicity and virulence in remarkable Botryosphaeriaceae species. Our results also support that Botryosphaeriaceae species could be used as an interesting biotechnological tool for lignocellulose fractionation and bioeconomy.
Topics: Virulence; Ascomycota; Plant Diseases
PubMed: 37142361
DOI: 10.1016/j.funbio.2023.03.004 -
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 -
Virulence Dec 2021Lipids are complex organic compounds made up of carbon, oxygen, and hydrogen. These play a diverse and intricate role in cellular processes like membrane trafficking,... (Review)
Review
Lipids are complex organic compounds made up of carbon, oxygen, and hydrogen. These play a diverse and intricate role in cellular processes like membrane trafficking, protein sorting, signal transduction, and bacterial infections. Both Gram-positive bacteria (.) and Gram-negative bacteria (, etc.) can hijack the various host-lipids and utilize them structurally as well as functionally to mount a successful infection. The pathogens can deploy with various arsenals to exploit host membrane lipids and lipid-associated receptors as an attachment for toxins' landing or facilitate their entry into the host cellular niche. Bacterial species like sp. can also modulate the host lipid metabolism to fetch its carbon source from the host. The sequential conversion of host membrane lipids into arachidonic acid and prostaglandin E2 due to increased activity of cPLA-2 and COX-2 upon bacterial infection creates immunosuppressive conditions and facilitates the intracellular growth and proliferation of bacteria. However, lipids' more debatable role is that they can also be a blessing in disguise. Certain host-lipids, especially sphingolipids, have been shown to play a crucial antibacterial role and help the host in combating the infections. This review shed light on the detailed role of host lipids in bacterial infections and the current understanding of the lipid in therapeutics. We have also discussed potential prospects and the need of the hour to help us cope in this race against deadly pathogens and their rapidly evolving stealthy virulence strategies.
Topics: Animals; Bacteria; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Host-Pathogen Interactions; Humans; Lipid Metabolism; Membrane Lipids; Mice; Signal Transduction; Virulence
PubMed: 33356849
DOI: 10.1080/21505594.2020.1869441 -
Memorias Do Instituto Oswaldo Cruz 2022Mycolicibacterium fortuitum is an opportunistic pathogen associated with human and animal infection worldwide. Studies concerning this species are mainly represented by...
BACKGROUND
Mycolicibacterium fortuitum is an opportunistic pathogen associated with human and animal infection worldwide. Studies concerning this species are mainly represented by case reports, some of them addressing drug susceptibility with a focus on a specific geographic region, so there is a gap in relation to the global epidemiological scenario.
OBJECTIVES
We aimed determine the global epidemiological scenario of M. fortuitum and analyse its traits associated with pathogenicity.
METHODS
Based on publicly available genomes of M. fortuitum and a genome from Brazil (this study), we performed a genomic epidemiology analysis and in silico and in vitro characterisation of the resistome and virulome of this species.
FINDINGS
Three main clusters were defined, one including isolates from the environment, human and animal infections recovered over nearly a century. An apparent intrinsic resistome comprises mechanisms associated with macrolides, beta-lactams, aminoglycosides and antitubercular drugs such as rifampin. Besides, the virulome presented Type VII secretion systems (T7SS), including ESX-1, ESX-3, ESX-4 and ESX-4-bis, some of which play a role on the virulence of Mycobacteriaceae species.
MAIN CONCLUSIONS
Here, M. fortuitum was revealed as a reservoir of an expressive intrinsic resistome, as well as a virulome that may contribute to its success as a global opportunist pathogen.
Topics: Antitubercular Agents; Brazil; Genomics; Humans; Virulence
PubMed: 35019071
DOI: 10.1590/0074-02760210247 -
Biochemical Society Transactions Jun 2021Interferon (IFN)-induced guanosine triphosphate hydrolysing enzymes (GTPases) have been identified as cornerstones of IFN-mediated cell-autonomous defence. Upon IFN... (Review)
Review
Interferon (IFN)-induced guanosine triphosphate hydrolysing enzymes (GTPases) have been identified as cornerstones of IFN-mediated cell-autonomous defence. Upon IFN stimulation, these GTPases are highly expressed in various host cells, where they orchestrate anti-microbial activities against a diverse range of pathogens such as bacteria, protozoan and viruses. IFN-induced GTPases have been shown to interact with various host pathways and proteins mediating pathogen control via inflammasome activation, destabilising pathogen compartments and membranes, orchestrating destruction via autophagy and the production of reactive oxygen species as well as inhibiting pathogen mobility. In this mini-review, we provide an update on how the IFN-induced GTPases target pathogens and mediate host defence, emphasising findings on protection against bacterial pathogens.
Topics: Animals; Bacteria; Bacterial Infections; GTP Phosphohydrolases; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferons; Signal Transduction; Virulence
PubMed: 34003245
DOI: 10.1042/BST20200900