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Cell Chemical Biology Feb 2016When it comes to lipid diversity, no bacterial genus approaches Mycobacterium. In this issue of Cell Chemical Biology, Burbaud et al. (2016) provide a multi-genic...
When it comes to lipid diversity, no bacterial genus approaches Mycobacterium. In this issue of Cell Chemical Biology, Burbaud et al. (2016) provide a multi-genic working model for the biosynthesis of trehalose polyphleate (TPP), one of the largest known lipids in mycobacteria. They demonstrate that this lipid is made by diverse mycobacterial species, including those of medical importance.
Topics: Lipids; Membrane Lipids; Mycobacterium; Mycobacterium Infections; Mycobacterium bovis; Mycobacterium tuberculosis; Trehalose
PubMed: 26971870
DOI: 10.1016/j.chembiol.2016.02.004 -
International Journal of Infectious... Aug 2020A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In...
OBJECTIVES
A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections.
METHODS
We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method.
RESULTS
We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively.
CONCLUSIONS
These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massiliense infections.
Topics: Actinomycetales Infections; Amikacin; Anti-Bacterial Agents; Clarithromycin; Doxycycline; Humans; Imipenem; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Mycobacteriaceae; Sequence Analysis, DNA; beta-Lactams
PubMed: 32526389
DOI: 10.1016/j.ijid.2020.06.007 -
Frontiers in Cellular and Infection... 2022Mycobacteria are members of the Actinomycetales order, and they are classified into one family, Mycobacteriaceae. More than 20 mycobacterial species cause disease in... (Review)
Review
Mycobacteria are members of the Actinomycetales order, and they are classified into one family, Mycobacteriaceae. More than 20 mycobacterial species cause disease in humans. The Mycobacterium group, called the complex (MTBC), has nine closely related species that cause tuberculosis in animals and humans. TB can be detected worldwide and one-fourth of the world's population is contaminated with tuberculosis. According to the WHO, about two million dies from it, and more than nine million people are newly infected with TB each year. () is the most potential causative agent of tuberculosis and prompts enormous mortality and morbidity worldwide due to the incompletely understood pathogenesis of human tuberculosis. Moreover, modern diagnostic approaches for human tuberculosis are inefficient and have many lacks, while MTBC species can modulate host immune response and escape host immune attacks to sustain in the human body. "Multi-omics" strategies such as genomics, transcriptomics, proteomics, metabolomics, and deep sequencing technologies could be a comprehensive strategy to investigate the pathogenesis of mycobacterial species in humans and offer significant discovery to find out biomarkers at the early stage of disease in the host. Thus, in this review, we attempt to understand an overview of the mission of "omics" approaches in mycobacterial pathogenesis, including tuberculosis, leprosy, and other mycobacterial diseases.
Topics: Animals; Genomics; Humans; Leprosy; Mycobacterium tuberculosis; Proteomics; Tuberculosis
PubMed: 35281437
DOI: 10.3389/fcimb.2022.792617 -
Nature Reviews. Microbiology Aug 2014Mycobacterium tuberculosis, which is the aetiological agent of tuberculosis, owes much of its success as a pathogen to its unique cell wall and unusual mechanism of... (Review)
Review
Mycobacterium tuberculosis, which is the aetiological agent of tuberculosis, owes much of its success as a pathogen to its unique cell wall and unusual mechanism of growth, which facilitate its adaptation to the human host and could have a role in clinical latency. Asymmetric growth and division increase population heterogeneity, which may promote antibiotic tolerance and the fitness of single cells. In this Review, we describe the unusual mechanisms of mycobacterial growth, cell wall biogenesis and division, and discuss how these processes might affect the survival of M. tuberculosis in vivo and contribute to the persistence of infection.
Topics: Cell Division; Cell Wall; Mycobacterium; Mycobacterium tuberculosis; Peptidoglycan
PubMed: 24998739
DOI: 10.1038/nrmicro3299 -
The European Respiratory Journal Sep 2017
Topics: Humans; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Phenotype
PubMed: 28954776
DOI: 10.1183/13993003.01380-2017 -
Saudi Medical Journal Jul 2021To optimize an enzyme-linked immunosorbent assay (ELISA) for measuring the HspX protein (α-crystallin) levels and then evaluate its correlation with the accumulation of...
OBJECTIVES
To optimize an enzyme-linked immunosorbent assay (ELISA) for measuring the HspX protein (α-crystallin) levels and then evaluate its correlation with the accumulation of lipid bodies in ( during hypoxia and exposure to nitric oxide.
METHODS
This study was conducted at Prince Sultan Military Medical City, Riyadh, Saudi Arabia between 2016 and 2017. We first optimized ELISA conditions for the detection of HspX. The optimization protocol focused on minimizing concentrations of the capture antibody, detection antibody, and conjugated secondary antibody, and determining the minimum detection limit of the antigen, HspX. Bacteria were grown either in shaking culture or in stationary flasks mimicking hypoxic environments. A standard Bradford assay was used to determine the total protein and HspX was detected using the optimized ELISA protocol. The effect of hypoxic environment and nitric oxide on the levels of HspX and lipid bodies, detected by staining with Nile red, was also evaluated.
RESULTS
An optimized ELISA protocol was established for the detection of HspX from . Exposure to nitric oxide and hypoxic conditions led to an increase in the levels of HspX protein. The increase in HspX associated with nitric oxide treatment and hypoxic conditions correlated with higher levels of lipid bodies mainly found in pathogenic mycobacteria.
CONCLUSIONS
The optimized ELISA protocol in this study can detect HspX protein levels in growing in normal and hypoxic environments. Importantly, hypoxia led to enhanced expression of HspX protein, which correlated with the enhanced production of lipid bodies. Lipid body production is a survival strategy of pathogenic mycobacteria.
Topics: Antigens, Bacterial; Bacterial Proteins; Enzyme-Linked Immunosorbent Assay; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Saudi Arabia
PubMed: 34187915
DOI: 10.15537/smj.2021.42.7.20200582 -
Infection Jun 2023
Topics: Humans; Abscess; Mycobacterium; Muscles; Nontuberculous Mycobacteria
PubMed: 36472781
DOI: 10.1007/s15010-022-01961-1 -
Emerging Microbes & Infections 2019Of the more than 190 distinct species of Mycobacterium genus, many are economically and clinically important pathogens of humans or animals. Among those mycobacteria... (Review)
Review
Of the more than 190 distinct species of Mycobacterium genus, many are economically and clinically important pathogens of humans or animals. Among those mycobacteria that infect humans, three species namely Mycobacterium tuberculosis (causative agent of tuberculosis), Mycobacterium leprae (causative agent of leprosy) and Mycobacterium abscessus (causative agent of chronic pulmonary infections) pose concern to global public health. Although antibiotics have been successfully developed to combat each of these, the emergence of drug-resistant strains is an increasing challenge for treatment and drug discovery. Here we describe the impact of the rapid expansion of genome sequencing and genome/pathway annotations that have greatly improved the progress of structure-guided drug discovery. We focus on the applications of comparative genomics, metabolomics, evolutionary bioinformatics and structural proteomics to identify potential drug targets. The opportunities and challenges for the design of drugs for M. tuberculosis, M. leprae and M. abscessus to combat resistance are discussed.
Topics: Animals; Bacterial Proteins; Computational Biology; Drug Discovery; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Molecular Sequence Annotation; Mycobacterium; Mycobacterium abscessus; Mycobacterium leprae; Mycobacterium tuberculosis; Protein Conformation; Proteomics; Sequence Analysis, DNA
PubMed: 30866765
DOI: 10.1080/22221751.2018.1561158 -
Seminars in Immunopathology Jun 2020Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing... (Review)
Review
Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.
Topics: Buruli Ulcer; Humans; Mycobacterium; Mycobacterium ulcerans; Skin
PubMed: 32100087
DOI: 10.1007/s00281-020-00790-4 -
International Journal of Molecular... Sep 2022The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that... (Review)
Review
The emergence of drug-resistant mycobacteria, including Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria (NTM), poses an increasing global threat that urgently demands the development of new potent anti-mycobacterial drugs. One of the approaches toward the identification of new drugs is fragment-based drug discovery (FBDD), which is the most ingenious among other drug discovery models, such as structure-based drug design (SBDD) and high-throughput screening. Specialized techniques, such as X-ray crystallography, nuclear magnetic resonance spectroscopy, and many others, are part of the drug discovery approach to combat the Mtb and NTM global menaces. Moreover, the primary drawbacks of traditional methods, such as the limited measurement of biomolecular toxicity and uncertain bioavailability evaluation, are successfully overcome by the FBDD approach. The current review focuses on the recognition of fragment-based drug discovery as a popular approach using virtual, computational, and biophysical methods to identify potent fragment molecules. FBDD focuses on designing optimal inhibitors against potential therapeutic targets of NTM and Mtb (PurC, ArgB, MmpL3, and TrmD). Additionally, we have elaborated on the challenges associated with the FBDD approach in the identification and development of novel compounds. Insights into the applications and overcoming the challenges of FBDD approaches will aid in the identification of potential therapeutic compounds to treat drug-sensitive and drug-resistant NTMs and Mtb infections.
Topics: Crystallography, X-Ray; Drug Design; Drug Discovery; Humans; Mycobacterium Infections; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 36142582
DOI: 10.3390/ijms231810669