ArticleJournal of bacteriology2005
FbpA-Dependent biosynthesis of trehalose dimycolate is required for the intrinsic multidrug resistance, cell wall structure, and colonial morphology of Mycobacterium smegmatis.
Article in Journal of bacteriology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
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- Metabolic Tagging Reveals Surface-Associated Lipoproteins in Mycobacteria.ACS infectious diseases · 2025Article
- Loss ofbioRxiv : the preprint server for biology · 2025Article
- Metabolic tagging reveals surface-associated lipoproteins in mycobacteria.bioRxiv : the preprint server for biology · 2025Article
- Age-Dependent Pleomorphism inMicroorganisms · 2025Article
- Tuberculosis vaccines and therapeutic drug: challenges and future directions.Molecular biomedicine · 2025Review
- Mycolyltransferase is important for biofilm formation and pathogenesis ofEmerging microbes & infections · 2024Article
- Optimizing antigen selection for the development of tuberculosis vaccines.Cell insight · 2024Review
- Article
- Improving the biotransformation efficiency of soybean phytosterols inSynthetic and systems biotechnology · 2022Article
- Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- Comparative transcriptome analysis reveals that deletion of CheY influences gene expressions of ABC transports and metabolism in Haemophilus parasuis.Functional & integrative genomics · 2021Article
- The Pup-Proteasome System Protects Mycobacteria from Antimicrobial Antifolates.Antimicrobial agents and chemotherapy · 2021Article
- Review
- Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis.Clinical microbiology reviews · 2020Review
- Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis.mSystems · 2020Article
- Enhancing the bioconversion of phytosterols to steroidal intermediates by the deficiency of kasB in the cell wall synthesis of Mycobacterium neoaurum.Microbial cell factories · 2020Article
- Article
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3 authors.
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Abstract
Ligation of mycolic acids to structural components of the mycobacterial cell wall generates a hydrophobic, impermeable barrier that provides resistance to toxic compounds such as antibiotics. Secreted proteins FbpA, FbpB, and FbpC attach mycolic acids to arabinogalactan, generating mycolic acid methyl esters (MAME) or trehalose, generating alpha,alpha'-trehalose dimycolate (TDM; also called cord factor). Our studies of Mycobacterium smegmatis showed that disruption of fbpA did not affect MAME levels but resulted in a 45% reduction of TDM. The fbpA mutant displayed increased sensitivity to both front-line tuberculosis-targeted drugs as well as other broad-spectrum antibiotics widely used for antibacterial chemotherapy. The irregular, hydrophobic surface of wild-type M. smegmatis colonies became hydrophilic and smooth in the mutant. While expression of M. smegmatis fbpA restored defects of the mutant, heterologous expression of the Mycobacterium tuberculosis fbpA gene was less effective. A single mutation in the M. smegmatis FbpA esterase domain inactivated its ability to provide antibiotic resistance. These data show that production of TDM by FbpA is essential for the intrinsic antibiotic resistance and normal colonial morphology of some mycobacteria and support the concept that FbpA-specific inhibitors, alone or in combination with other antibiotics, could provide an effective treatment to tuberculosis and other mycobacterial diseases.
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