trehalose-monomycolate and Tuberculosis

trehalose-monomycolate has been researched along with Tuberculosis* in 6 studies

Reviews

1 review(s) available for trehalose-monomycolate and Tuberculosis

ArticleYear
Tuberculosis vaccine candidates based on mycobacterial cell envelope components.
    Tuberculosis (Edinburgh, Scotland), 2019, Volume: 115

    Even after decades searching for a new and more effective vaccine against tuberculosis, the scientific community is still pursuing this goal due to the complexity of its causative agent, Mycobacterium tuberculosis (Mtb). Mtb is a microorganism with a robust variety of survival mechanisms that allow it to remain in the host for years. The structure and nature of the Mtb envelope play a leading role in its resistance and survival. Mtb has a perfect machinery that allows it to modulate the immune response in its favor and to adapt to the host's environmental conditions in order to remain alive until the moment to reactivate its normal growing state. Mtb cell envelope protein, carbohydrate and lipid components have been the subject of interest for developing new vaccines because most of them are responsible for the pathogenicity and virulence of the bacteria. Many indirect evidences, mainly derived from the use of monoclonal antibodies, support the potential protective role of Mtb envelope components. Subunit and DNA vaccines, lipid extracts, liposomes and membrane vesicle formulations are some examples of technologies used, with encouraging results, to evaluate the potential of these antigens in the protective response against Mtb.

    Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Bacterial Capsules; Bacterial Proteins; BCG Vaccine; Cell Membrane; Cell Wall; Cord Factors; Humans; Mice; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines; Virulence

2019

Other Studies

5 other study(ies) available for trehalose-monomycolate and Tuberculosis

ArticleYear
Protein kinases PknA and PknB independently and coordinately regulate essential Mycobacterium tuberculosis physiologies and antimicrobial susceptibility.
    PLoS pathogens, 2020, Volume: 16, Issue:4

    The Mycobacterium tuberculosis Ser/Thr protein kinases PknA and PknB are essential for growth and have been proposed as possible drug targets. We used a titratable conditional depletion system to investigate the functions of these kinases. Depletion of PknA or PknB or both kinases resulted in growth arrest, shortening of cells, and time-dependent loss of acid-fast staining with a concomitant decrease in mycolate synthesis and accumulation of trehalose monomycolate. Depletion of PknA and/or PknB resulted in markedly increased susceptibility to β-lactam antibiotics, and to the key tuberculosis drug rifampin. Phosphoproteomic analysis showed extensive changes in protein phosphorylation in response to PknA depletion and comparatively fewer changes with PknB depletion. These results identify candidate substrates of each kinase and suggest specific and coordinate roles for PknA and PknB in regulating multiple essential physiologies. These findings support these kinases as targets for new antituberculosis drugs and provide a valuable resource for targeted investigation of mechanisms by which protein phosphorylation regulates pathways required for growth and virulence in M. tuberculosis.

    Topics: Antitubercular Agents; Bacterial Proteins; Cord Factors; Gene Expression Regulation, Bacterial; Humans; Mycobacterium tuberculosis; Protein Serine-Threonine Kinases; Tuberculosis

2020
A piperidinol-containing molecule is active against
    The Journal of biological chemistry, 2019, 11-15, Volume: 294, Issue:46

    Topics: Antitubercular Agents; Bacterial Proteins; Biological Transport; Cord Factors; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Models, Molecular; Mycobacterium tuberculosis; Mycolic Acids; Piperidines; Tuberculosis

2019
Imaging mycobacterial growth and division with a fluorogenic probe.
    Proceedings of the National Academy of Sciences of the United States of America, 2018, 05-15, Volume: 115, Issue:20

    Control and manipulation of bacterial populations requires an understanding of the factors that govern growth, division, and antibiotic action. Fluorescent and chemically reactive small molecule probes of cell envelope components can visualize these processes and advance our knowledge of cell envelope biosynthesis (e.g., peptidoglycan production). Still, fundamental gaps remain in our understanding of the spatial and temporal dynamics of cell envelope assembly. Previously described reporters require steps that limit their use to static imaging. Probes that can be used for real-time imaging would advance our understanding of cell envelope construction. To this end, we synthesized a fluorogenic probe that enables continuous live cell imaging in mycobacteria and related genera. This probe reports on the mycolyltransferases that assemble the mycolic acid membrane. This peptidoglycan-anchored bilayer-like assembly functions to protect these cells from antibiotics and host defenses. Our probe, quencher-trehalose-fluorophore (QTF), is an analog of the natural mycolyltransferase substrate. Mycolyltransferases process QTF by diverting their normal transesterification activity to hydrolysis, a process that unleashes fluorescence. QTF enables high contrast continuous imaging and the visualization of mycolyltransferase activity in cells. QTF revealed that mycolyltransferase activity is augmented before cell division and localized to the septa and cell poles, especially at the old pole. This observed localization suggests that mycolyltransferases are components of extracellular cell envelope assemblies, in analogy to the intracellular divisomes and polar elongation complexes. We anticipate QTF can be exploited to detect and monitor mycobacteria in physiologically relevant environments.

    Topics: Bacterial Proteins; Cell Division; Cell Wall; Cord Factors; Corynebacterium glutamicum; Fluorescence; Fluorescent Dyes; Humans; Image Processing, Computer-Assisted; Mycobacterium tuberculosis; Peptidoglycan; Tuberculosis

2018
Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3.
    PloS one, 2013, Volume: 8, Issue:4

    Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP) and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This 'genetic phenotype' was further confirmed by a 'chemical phenotype', whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice.

    Topics: Animals; Antitubercular Agents; Bacterial Proteins; Bridged Bicyclo Compounds, Heterocyclic; Chromatography, Thin Layer; Cord Factors; Disease Models, Animal; Dogs; Drug Resistance, Bacterial; Genotype; Hep G2 Cells; Humans; Kinetics; Mice; Microbial Sensitivity Tests; Microbial Viability; Mutation; Mycobacterium tuberculosis; Pyrazoles; Rats; Spiro Compounds; Treatment Outcome; Tuberculosis

2013
Diverse humoral immune responses and changes in IgG antibody levels against mycobacterial lipid antigens in active tuberculosis.
    Microbiology (Reading, England), 2005, Volume: 151, Issue:Pt 6

    Humoral immune responses of active TB patients against six mycobacterial lipid antigens [trehalose 6,6'-dimycolate (TDM) from Mycobacterium bovis BCG (TDM-T) and Mycobacterium avium complex (TDM-M), trehalose 6-monomycolate (TMM) from M. bovis BCG (TMM-T) and M. avium complex (TMM-M), triacyl (PL-2) and tetraacyl (PL-1) phosphatidylinositol dimannosides] were examined by ELISA. IgG antibodies of TB patients with active disease reacted against the six lipid antigens distinctively, but heterogeneously. If tests were combined and an overall positive was scored cumulatively when any one of the six tests was positive, a good discrimination between patient and normal subject was obtained. A positive result in any one of the six tests was obtained in 91.5% of all 924 hospitalized patients and 93.3% of 210 patients at their first visit to the outpatient clinic. The IgG antibody response differed considerably from patient to patient, and the response patterns were grouped into several types. IgG antibody levels paralleled the bacterial burden; however, the smear-negative (culture-positive) patient group also showed high positive rates and mean ELISA DeltaA values against the six lipid antigens. There were also marked differences in positive rate and mean DeltaA values between cavity-positive and -negative groups, the former being higher than the latter. After anti-TB chemotherapy was initiated, IgG antibody levels decreased dramatically, paralleling the decrease in the amount of excretion of bacteria. Since multiple-antigen ELISA using particular lipid antigens was highly sensitive, and IgG antibody levels vary greatly at different stages of the disease, this technique is applicable for early diagnosis of smear-negative (and -positive) active TB and the prognosis for completion of anti-TB chemotherapy.

    Topics: Adult; Aged; Antibodies, Bacterial; Antigens, Bacterial; Cord Factors; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Inpatients; Japan; Kinetics; Lipids; Male; Middle Aged; Mycobacterium; Mycobacterium avium Complex; Mycobacterium bovis; Mycobacterium tuberculosis; Outpatients; Phosphatidylinositols; Time Factors; Tuberculosis

2005
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