ArticleAntimicrobial agents and chemotherapy2009
The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 3 of them syntheses that pooled it.
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83 citing papers in PubMed, 3 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019Guideline
- Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis.The Journal of antimicrobial chemotherapy · 2014Pooled it
- MetaMerge: scaling up genome-scale metabolic reconstructions with application to Mycobacterium tuberculosis.Genome biology · 2012Pooled it
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- Pilot Study on the Effects of First-Line Antituberculosis Drugs and Their Combinations on Selected Reproductive Endpoints in Female Rats.Life (Basel, Switzerland) · 2026Article
- Enhancing the bioconversion of phytosterols to 22-hydroxy-23,24- bisnorchol-4-ene-3-one in Mycobacterium neoaurum ZS-15 through genetic modification of kstD1 and wecA.Microbial cell factories · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- ACA kills Mycobacterium tuberculosis and M. bovis by targeting cell wall core assembling protein CpsA.Communications biology · 2025Article
- Common Biological Properties ofACS infectious diseases · 2025Article
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- Increased proportion of growth-arrested bacilli in acidic pH adaptation promotesbioRxiv : the preprint server for biology · 2025Article
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- Structural insights into terminal arabinosylation of mycobacterial cell wall arabinan.Nature communications · 2025Article
- Tuberculosis vaccines and therapeutic drug: challenges and future directions.Molecular biomedicine · 2025Review
- Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Flavin and deazaflavin biosynthesis in mycobacteria: relevance to physiology, implications for drug discovery, MR-1 antigenicity, and vaccine development.Frontiers in immunology · 2025Review
- A scoping review about smoking, smoking cessation and their effects on anti-tuberculosis agents: insights into drug metabolisms, safety, and effectiveness.Frontiers in pharmacology · 2025Review
23 more citing papers are in PubMed but not listed here.
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4 authors at 3 institutions in 2 countries.
Funding
Abstract
Ethambutol (EMB) is an antimycobacterial drug used extensively for the treatment of tuberculosis caused by Mycobacterium tuberculosis. EMB targets the biosynthesis of the cell wall, inhibiting the synthesis of both arabinogalactan and lipoarabinomannan (LAM), and is assumed to act via inhibition of three arabinosyltransferases: EmbA, EmbB, and EmbC. EmbA and EmbB are required for the synthesis of arabinogalactan, and at least one enzyme (M. tuberculosis EmbA [EmbA(Mt)]) is essential in M. tuberculosis. EmbC(Mt) is also essential for the viability of M. tuberculosis but is involved in the synthesis of LAM. We show that mutations in EmbC(Mt) that reduce its arabinosyltransferase activity result in increased sensitivity to EMB and the production of smaller LAM species in M. tuberculosis. Overexpression of EmbC(Mt) was not tolerated in M. tuberculosis, but overexpression of Mycobacterium smegmatis EmbC (EmbC(Ms)) led to EMB resistance and the production of larger LAM species in M. tuberculosis. Treatment of wild-type M. tuberculosis strains with EMB led to inhibition of LAM synthesis, resulting in the production of smaller species of LAM. In contrast, no change in LAM production was seen in EMB-resistant strains. Overexpression of EmbB(Ms) in M. tuberculosis also resulted in EMB resistance, but at a lower level than that caused by EmbC(Ms). Overexpression of EmbA(Mt) in M. tuberculosis had no effect on EMB resistance. Thus, there is a direct correlation between EmbC activity and EMB resistance, as well as between EmbC activity and the size of the LAM species produced, confirming that EmbC is one of the cellular targets of EMB action.
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