ArticleThe Journal of biological chemistry2014
Biosynthesis and translocation of unsulfated acyltrehaloses in Mycobacterium tuberculosis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
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- The mycobacterial ATP burst is a lysis artifact and serves as an assay for drug-induced cell wall damage.bioRxiv : the preprint server for biology · 2025Article
- MmpL12 transports lipooligosaccharides and impacts virulence inMicrobiology (Reading, England) · 2025Article
- Deciphering the role of VapBC13 and VapBC26 toxin antitoxin systems in the pathophysiology of Mycobacterium tuberculosis.Communications biology · 2024Article
- Marine sponge microbe provides insights into evolution and virulence of the tubercle bacillus.PLoS pathogens · 2024Article
- Intricate link between siderophore secretion and drug efflux inAntimicrobial agents and chemotherapy · 2023Article
- Bedquiline Resistance Mutations: Correlations with Drug Exposures and Impact on the Proteome in M. tuberculosis.Antimicrobial agents and chemotherapy · 2023Article
- Target Identification in Anti-Tuberculosis Drug Discovery.International journal of molecular sciences · 2023Review
- Understanding the Phage-Host Interaction Mechanism toward Improving the Efficacy of Current Antibiotics inBiomedicines · 2023Article
- Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10.Communications biology · 2022Article
- Unveiling the Biosynthetic Pathway for Short Mycolic Acids in Nontuberculous Mycobacteria: Mycobacterium smegmatis MSMEG_4301 and Its Ortholog Mycobacterium abscessus MAB_1915 Are Essential for the Synthesis of α'-Mycolic Acids.Microbiology spectrum · 2022Article
- Mechanistic insights into the antimycobacterial action of unani formulation, Qurs Sartan Kafoori.Journal of traditional and complementary medicine · 2022Article
- Commonalities ofFrontiers in immunology · 2022Article
- Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell Envelope.Chemical reviews · 2021Review
- Complete Characterization of Polyacyltrehaloses fromBiochemistry · 2021Article
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- Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis.European journal of medicinal chemistry · 2020Article
- The final assembly of trehalose polyphleates takes place within the outer layer of the mycobacterial cell envelope.The Journal of biological chemistry · 2020Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
A number of species-specific polymethyl-branched fatty acid-containing trehalose esters populate the outer membrane of Mycobacterium tuberculosis. Among them, 2,3-diacyltrehaloses (DAT) and penta-acyltrehaloses (PAT) not only play a structural role in the cell envelope but also contribute to the ability of M. tuberculosis to multiply and persist in the infected host, promoting the intracellular survival of the bacterium and modulating host immune responses. The nature of the machinery, topology, and sequential order of the reactions leading to the biosynthesis, assembly, and export of these complex glycolipids to the cell surface are the object of the present study. Our genetic and biochemical evidence corroborates a model wherein the biosynthesis and translocation of DAT and PAT to the periplasmic space are coupled and topologically split across the plasma membrane. The formation of DAT occurs on the cytosolic face of the plasma membrane through the action of PapA3, FadD21, and Pks3/4; that of PAT occurs on the periplasmic face via transesterification reactions between DAT substrates catalyzed by the acyltransferase Chp2 (Rv1184c). The integral membrane transporter MmpL10 is essential for DAT to reach the cell surface, and its presence in the membrane is required for Chp2 to be active. Disruption of mmpL10 or chp2 leads to an important build-up of DAT inside the cells and to the formation of a novel form of unsulfated acyltrehalose esterified with polymethyl-branched fatty acids normally found in sulfolipids that is translocated to the cell surface.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.