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Nature Microbiology Sep 2023
Topics: Humans; Mycobacterium tuberculosis; Educational Personnel
PubMed: 37587200
DOI: 10.1038/s41564-023-01454-3 -
Future Microbiology Dec 2023Almost 3% of the proteins of (), the main causative agent of human tuberculosis, are lipoproteins. These lipoproteins are characteristic of the mycobacterial cell... (Review)
Review
Almost 3% of the proteins of (), the main causative agent of human tuberculosis, are lipoproteins. These lipoproteins are characteristic of the mycobacterial cell envelope and participate in many mechanisms involved in the pathogenesis of . In this review, the authors provide an updated analysis of lipoproteins and categorize them according to their demonstrated or predicted functions, including transport of compounds to and from the cytoplasm, biosynthesis of the mycobacterial cell envelope, defense and resistance mechanisms, enzymatic activities and signaling pathways. In addition, this updated analysis revealed that at least 40% of lipoproteins are glycosylated.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis; Cell Membrane; Cell Wall; Lipoproteins; Bacterial Proteins
PubMed: 37962486
DOI: 10.2217/fmb-2023-0088 -
Microbiology (Reading, England) May 2024(Mtb) senses and adapts to host environmental cues as part of its pathogenesis. One important cue sensed by Mtb is the acidic pH of its host niche - the macrophage.... (Review)
Review
(Mtb) senses and adapts to host environmental cues as part of its pathogenesis. One important cue sensed by Mtb is the acidic pH of its host niche - the macrophage. Acidic pH induces widespread transcriptional and metabolic remodelling in Mtb. These adaptations to acidic pH can lead Mtb to slow its growth and promote pathogenesis and antibiotic tolerance. Mutants defective in pH-dependent adaptations exhibit reduced virulence in macrophages and animal infection models, suggesting that chemically targeting these pH-dependent pathways may have therapeutic potential. In this review, we discuss mechanisms by which Mtb regulates its growth and metabolism at acidic pH. Additionally, we consider the therapeutic potential of disrupting pH-driven adaptations in Mtb and review the growing class of compounds that exhibit pH-dependent activity or target pathways important for adaptation to acidic pH.
Topics: Mycobacterium tuberculosis; Hydrogen-Ion Concentration; Adaptation, Physiological; Animals; Humans; Tuberculosis; Macrophages; Virulence; Gene Expression Regulation, Bacterial; Bacterial Proteins; Antitubercular Agents
PubMed: 38717801
DOI: 10.1099/mic.0.001458 -
Microbes and Infection Apr 2020
Topics: Antitubercular Agents; Humans; Mycobacterium tuberculosis; Tuberculosis
PubMed: 31629824
DOI: 10.1016/j.micinf.2019.09.003 -
Frontiers in Cellular and Infection... 2022Bacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious... (Review)
Review
Bacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious risk the possibility to treat infectious diseases in the near future. One of the infection at higher risk to become incurable is tuberculosis, due to the few drugs available in the market against . Drug resistance in this species is usually due to point mutations in the drug target or in proteins required to activate prodrugs. However, another interesting and underexplored aspect of bacterial physiology with important impact on drug susceptibility is represented by the changes in transcriptional regulation following drug exposure. The main regulators involved in this phenomenon in are the sigma factors, and regulators belonging to the WhiB, GntR, XRE, Mar and TetR families. Better understanding the impact of these regulators in survival to drug treatment might contribute to identify new drug targets and/or to design new strategies of intervention.
Topics: Drug Resistance, Multiple, Bacterial; Gene Expression Regulation; Humans; Mycobacterium tuberculosis; Prodrugs; Tuberculosis, Lymph Node
PubMed: 36118045
DOI: 10.3389/fcimb.2022.990312 -
Frontiers in Cellular and Infection... 2019
Topics: Host-Pathogen Interactions; Mycobacterium tuberculosis; Tuberculosis; Virulence
PubMed: 31649893
DOI: 10.3389/fcimb.2019.00331 -
Nature Communications Dec 2023Mycobacterium tuberculosis has evolved several mechanisms to counter host defense arsenals for its proliferation. Here we report that M. tuberculosis employs a...
Mycobacterium tuberculosis has evolved several mechanisms to counter host defense arsenals for its proliferation. Here we report that M. tuberculosis employs a multi-pronged approach to modify host epigenetic machinery for its survival. It secretes methyltransferase (MTase) Rv2067c into macrophages, trimethylating histone H3K79 in a non-nucleosomal context. Rv2067c downregulates host MTase DOT1L, decreasing DOT1L-mediated nucleosomally added H3K79me3 mark on pro-inflammatory response genes. Consequent inhibition of caspase-8-dependent apoptosis and enhancement of RIPK3-mediated necrosis results in increased pathogenesis. In parallel, Rv2067c enhances the expression of SESTRIN3, NLRC3, and TMTC1, enabling the pathogen to overcome host inflammatory and oxidative responses. We provide the structural basis for differential methylation of H3K79 by Rv2067c and DOT1L. The structures of Rv2067c and DOT1L explain how their action on H3K79 is spatially and temporally separated, enabling Rv2067c to effectively intercept the host epigenetic circuit and downstream signaling.
Topics: Methyltransferases; Mycobacterium tuberculosis; Methylation; Histones; Epigenesis, Genetic
PubMed: 38129415
DOI: 10.1038/s41467-023-43940-6 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Tuberculosis; Mycobacterium tuberculosis
PubMed: 38089813
DOI: 10.3389/fcimb.2023.1332084 -
Critical Reviews in Microbiology Feb 2021Tuberculosis (TB) is a fatal epidemic disease usually caused by (). Pervasive latent infection, multidrug- and extensively drug-resistant tuberculosis (MDR- and... (Review)
Review
Tuberculosis (TB) is a fatal epidemic disease usually caused by (). Pervasive latent infection, multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB), and TB/HIV co-infection make TB a global health problem, which emphasises the design and development of efficient vaccines and diagnostic biomarkers. Extracellular vesicles (EVs) secretion is a conserved phenomenon in all the domains of life. Various cargos such as nucleic acids, toxins, lipoproteins, and enzymes have been recognised in these nano-sized vesicles that may be involved in bacterial physiology and pathogenesis. The intrinsic adjuvant effect, native immunogenic cargo, sensing by host immune cells, circulation in all body fluids, and comprehensive distribution of antigens introduce EVs as a promising tool for designing novel vaccines, diagnostic biomarkers, and drug delivery systems. Genetic engineering of the EV-producing bacteria and the subsequent production of proper EVs could facilitate the development of the EV-based therapeutic applications. Recently, it was demonstrated that thick-walled mycobacteria release EVs, which contain immunodominant cargos such as lipoglycans and lipoproteins. The present article is a comprehensive review on the recent findings of EVs biology and the exploitation of EVs for the vaccine technology and diagnostic methods.
Topics: Animals; Extracellular Vesicles; Humans; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines; Vaccines
PubMed: 33044878
DOI: 10.1080/1040841X.2020.1830749 -
Microbiology and Molecular Biology... Nov 2020Pathogenic mycobacteria cause chronic and acute diseases ranging from human tuberculosis (TB) to nontubercular infections. causes both acute and chronic human... (Review)
Review
Pathogenic mycobacteria cause chronic and acute diseases ranging from human tuberculosis (TB) to nontubercular infections. causes both acute and chronic human tuberculosis. Environmentally acquired nontubercular mycobacteria (NTM) cause chronic disease in humans and animals. Not surprisingly, NTM and often use shared molecular mechanisms to survive within the host. The ESX-1 system is a specialized secretion system that is essential for virulence and is functionally conserved between and is an NTM found in both salt water and freshwater that is often used to study mycobacterial virulence. Since the discovery of the secretion system in 2003, the use of both and has defined the conserved molecular mechanisms underlying protein secretion and the lytic and regulatory activities of the ESX-1 system. Here, we review the trajectory of the field, including key discoveries regarding the ESX-1 system. We highlight the contributions of studies and the conserved and unique aspects of the ESX-1 secretion system.
Topics: Animals; Bacterial Proteins; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Humans; Models, Biological; Mycobacterium marinum; Mycobacterium tuberculosis; Protein Transport; Tuberculosis; Type VII Secretion Systems; Virulence
PubMed: 32878966
DOI: 10.1128/MMBR.00082-19