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Microbiology Spectrum Oct 2014Proteasomes are ATP-dependent, barrel-shaped proteases found in all three domains of life. In eukaryotes, proteins are typically targeted for degradation by... (Review)
Review
Proteasomes are ATP-dependent, barrel-shaped proteases found in all three domains of life. In eukaryotes, proteins are typically targeted for degradation by posttranslational modification with the small protein ubiquitin. In 2008, the first bacterial protein modifier, Pup (prokaryotic ubiquitin-like protein), was identified in Mycobacterium tuberculosis. Functionally analogous to ubiquitin, conjugation with Pup serves as a signal for degradation by the mycobacterial proteasome. Proteolysis-dependent and -independent functions of the M. tuberculosis proteasome are essential for virulence of this successful pathogen. In this article we describe the discovery of the proteasome as a key player in tuberculosis pathogenesis and the biology and biochemistry of the Pup-proteasome system.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Mycobacterium tuberculosis; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Proteolysis; Ubiquitins
PubMed: 26104367
DOI: 10.1128/microbiolspec.MGM2-0008-2013 -
Archives of Microbiology Aug 2015Many pathogenic bacteria express filamentous appendages, termed pili, on their surface. These organelles function in several important bacterial processes, including... (Review)
Review
Many pathogenic bacteria express filamentous appendages, termed pili, on their surface. These organelles function in several important bacterial processes, including mediating bacterial interaction with, and colonization of the host, signalling events, locomotion, DNA uptake, electric conductance, and biofilm formation. In the last decade, it has been established that the tuberculosis-causing bacterium, Mycobacterium tuberculosis, produces two pili types: curli and type IV pili. In this paper, we review studies on M. tuberculosis pili, highlighting their structure and biological significance to M. tuberculosis pathogenesis, and discuss their potential as targets for therapeutic intervention and diagnostic test development.
Topics: Bacterial Adhesion; Fimbriae, Bacterial; Mycobacterium tuberculosis; Tuberculosis
PubMed: 25975850
DOI: 10.1007/s00203-015-1117-0 -
Current Microbiology Jul 2015NarGHJI operon encodes a nitrate reductase that can reduce nitrate to nitrite. This process enhances bacterial survival by nitrate respiration under anaerobic... (Review)
Review
NarGHJI operon encodes a nitrate reductase that can reduce nitrate to nitrite. This process enhances bacterial survival by nitrate respiration under anaerobic conditions. NarGHJI operon exists in many bacteria, especially saprophytic bacteria living in soil which play a key role in the nitrogen cycle. Most actinomycetes, including Mycobacterium tuberculosis, possess NarGHJI operons. M. tuberculosis is a facultative intracellular pathogen that expands in macrophages and has the ability to persist in a non-replicative form in granuloma lifelong. Nitrogen and nitrogen compounds play crucial roles in the struggle between M. tuberculosis and host. M. tuberculosis can use nitrate as a final electron acceptor under anaerobic conditions to enhance its survival. In this article, we reviewed the mechanisms regulating nitrate reductase expression and affecting its activity. Potential genes involved in regulating the nitrate reductase expression in M. tuberculosis were identified. The conserved NarG might be an alternative mycobacterium taxonomic marker.
Topics: Aerobiosis; Anaerobiosis; Mycobacterium tuberculosis; Nitrate Reductase; Nitrates; Nitrites; Operon; Phylogeny
PubMed: 25980349
DOI: 10.1007/s00284-015-0838-2 -
The Indian Journal of Medical Research Dec 2017Tuberculosis (TB) remains an escalating problem worldwide. The current diagnostic methods do not always guarantee reliable diagnosis. TB treatment is a time-consuming... (Review)
Review
Tuberculosis (TB) remains an escalating problem worldwide. The current diagnostic methods do not always guarantee reliable diagnosis. TB treatment is a time-consuming process that requires the use of several chemotherapeutics, to which mycobacteria are becoming increasingly resistant. This article focuses on the potential utility of biomarkers of mycobacterial origin with potential implications for TB diagnosis. Properly standardized indicators could become new diagnostic tools, improving and streamlining the identification of Mycobacterium tuberculosis infection and the implementation of appropriate therapy. These markers can also potentially provide a quick confirmation of effectiveness of new anti-mycobacterial drugs and TB vaccines, leading to a possible application in practice.
Topics: Antitubercular Agents; Biomarkers; Humans; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines
PubMed: 29664027
DOI: 10.4103/ijmr.IJMR_1441_16 -
Journal of Infection and Public Health Apr 2021Mycobacterium tuberculosis, the bacterium that causes tuberculosis, has long been an unpleasant neighbour of humans. Following transmission of the bacterium from... (Review)
Review
Mycobacterium tuberculosis, the bacterium that causes tuberculosis, has long been an unpleasant neighbour of humans. Following transmission of the bacterium from patients with active infection, new hosts do not immediately develop symptoms, as M. tuberculosis initially remains quiescent. However, it is eventually triggered, leading to the infection of other individuals. Humans are the exclusive host, and the rapid proliferation of the human population worldwide along with increasing globalisation have contributed to the pathogen's persistence, as have the survival strategies employed by M. tuberculosis, especially its resistance to several antimicrobials. Defeating this enemy will require novel approaches.
Topics: Antitubercular Agents; Humans; Mycobacterium tuberculosis; Tuberculosis
PubMed: 33743373
DOI: 10.1016/j.jiph.2021.01.005 -
Human Molecular Genetics Apr 2021For centuries, the Mycobacterium tuberculosis complex (MTBC) has infected numerous populations, both human and non-human, causing symptomatic tuberculosis (TB) in some... (Review)
Review
For centuries, the Mycobacterium tuberculosis complex (MTBC) has infected numerous populations, both human and non-human, causing symptomatic tuberculosis (TB) in some hosts. Research investigating the MTBC and how it has evolved with its host over time is sparse and has not resulted in many significant findings. There are even fewer studies investigating adaptation of the human host susceptibility to TB and these have largely focused on genome-wide association and candidate gene association studies. However, results emanating from these association studies are rarely replicated and appear to be population specific. It is, therefore, necessary to relook at the approach taken to investigate the relationship between the MTBC and the human host. Understanding that the evolution of the pathogen is coupled to the evolution of the host might be the missing link needed to effectively investigate their relationship. We hypothesize that this knowledge will bolster future efforts in combating the disease.
Topics: Adaptation, Physiological; Animals; DNA; Genetics, Population; Genome-Wide Association Study; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Tuberculosis
PubMed: 33258469
DOI: 10.1093/hmg/ddaa254 -
Nature Reviews. Microbiology Nov 2014Several major pathogens, including Mycobacterium tuberculosis, parasitize host cells and exploit host-derived nutrients to sustain their own metabolism. Although the... (Review)
Review
Several major pathogens, including Mycobacterium tuberculosis, parasitize host cells and exploit host-derived nutrients to sustain their own metabolism. Although the carbon sources that are used by M. tuberculosis have been extensively studied, the mechanisms by which mycobacteria capture and metabolize nitrogen, which is another essential constituent of biomolecules, have only recently been revisited. In this Progress article, we discuss central nitrogen metabolism in M. tuberculosis, the mechanisms that are used by this pathogen to obtain nitrogen from its host and the potential role of nitrogen capture and metabolism in virulence.
Topics: Carbon; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Nitrogen; Tuberculosis; Virulence
PubMed: 25244084
DOI: 10.1038/nrmicro3349 -
Microbiology Spectrum Mar 2017Reversible protein phosphorylation is the most common type of epigenetic posttranslational modification in living cells used as a major regulation mechanism of... (Review)
Review
Reversible protein phosphorylation is the most common type of epigenetic posttranslational modification in living cells used as a major regulation mechanism of biological processes. The Mycobacterium tuberculosis genome encodes for 11 serine/threonine protein kinases that are responsible for sensing environmental signals to coordinate a cellular response to ensure the pathogen's infectivity, survival, and growth. To overcome killing mechanisms generated within the host during infection, M. tuberculosis enters a state of nonreplicating persistence that is characterized by arrested growth, limited metabolic activity, and phenotypic resistance to antimycobacterial drugs. In this article we focus our attention on the role of M. tuberculosis serine/threonine protein kinases in sensing the host environment to coordinate the bacilli's physiology, including growth, cell wall components, and central metabolism, to establish a persistent infection.
Topics: Animals; Epigenesis, Genetic; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Phosphorylation; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases
PubMed: 28281439
DOI: 10.1128/microbiolspec.TBTB2-0005-2015 -
Advances in Experimental Medicine and... 2017The Mycobacterium tuberculosis Complex (MTBC) consists of a clonal group of several mycobacterial lineages pathogenic to a range of different mammalian hosts. In this... (Review)
Review
The Mycobacterium tuberculosis Complex (MTBC) consists of a clonal group of several mycobacterial lineages pathogenic to a range of different mammalian hosts. In this chapter, we discuss the origins and the evolutionary forces shaping the genomic diversity of the human-adapted MTBC. Advances in whole-genome sequencing have brought invaluable insights into the macro-evolution of the MTBC, and the biogeographical distribution of the different MTBC lineages, the phylogenetic relationships between these lineages. Moreover, micro-evolutionary processes start to be better understood, including those influencing bacterial mutation rates and those governing the fate of new mutations emerging within patients during treatment. Current genomic and epidemiological evidence reflect the fact that, through ecological specialization, the MTBC affecting humans became an obligate and extremely well-adapted human pathogen. Identifying the adaptive traits of human-adapted MTBC and unraveling the bacterial loci that interact with human genomic variation might help identify new targets for developing better vaccines and designing more effective treatments.
Topics: Adaptation, Physiological; Biological Coevolution; Evolution, Molecular; Genetic Variation; Genome, Bacterial; Genome, Human; Genotype; Host-Pathogen Interactions; Humans; Mycobacterium tuberculosis; Phenotype; Phylogeny; Phylogeography; Tuberculosis; Virulence
PubMed: 29116627
DOI: 10.1007/978-3-319-64371-7_1 -
Biological Chemistry Feb 2020Tuberculosis caused by Mycobacterium tuberculosis remains a serious threat to public health. The M. tuberculosis cell envelope is closely related to its virulence and... (Review)
Review
Tuberculosis caused by Mycobacterium tuberculosis remains a serious threat to public health. The M. tuberculosis cell envelope is closely related to its virulence and drug resistance. Mycobacterial membrane large proteins (MmpL) are lipid-transporting proteins of the efflux pump resistance nodulation cell division (RND) superfamily with lipid substrate specificity and non-transport lipid function. Mycobacterial membrane small proteins (MmpS) are small regulatory proteins, and they are also responsible for some virulence-related effects as accessory proteins of MmpL. The MmpL transporters are the candidate targets for the development of anti-tuberculosis drugs. This article summarizes the structure, function, phylogenetics of M. tuberculosis MmpL/S proteins and their roles in host immune response, inhibitors and regulatory system.
Topics: Antitubercular Agents; Membrane Transport Proteins; Microbial Sensitivity Tests; Mycobacterium tuberculosis
PubMed: 31652116
DOI: 10.1515/hsz-2019-0326