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The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol

Nature Medicine volume 3, pages 567–570 (1997)Cite this article

Abstract

Ethambutol (EMB), a frontline antituberculous drug, targets the mycobacterial cell wall, a unique structure among prokaryotes which consists of an outer layer of mycolic acids covalently bound to peptidoglycan via the arabinogalactan. EMB inhibits the polymerization of cell wall arabinan, and results in the accumulation of the lipid carrier decaprenol phosphoarabinose1,2, which suggests that the drug interferes with the transfer of arabinose to the cell wall acceptor. Unfortunately, resistance to EMB has been described in up to 4% of clinical isolates of Mycobacterium tuberculosis and is prevalent among isolates from patients with multidrug-resistant tuberculosis3. We used resistance to EMB as a tool to identify genes participating in the biosynthesis of the mycobacterial cell wall. This approach led to the identification of the embCAB gene cluster, recently proposed to encode for mycobacterial arabinosyl transferases4. Resistance to EMB results from an accumulation of genetic events determining overexpression of the Emb protein(s), structural mutation in EmbB, or both. Further characterization of these proteins might provide information on targets for new chemotherapeutic agents and might help development of diagnostic strategies for the detection of resistant M. tuberculosis.

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Authors and Affiliations

  1. Institute for Medical Microbiology, University of Bern, 3010, Bern, Switzerland

    Amalio Telenti, Wolfgang J. Philipp, Claudia Bernasconi & Brigitte Wieles

  2. Department of Microbiology and Immunology and Howard Hughes Medical Research Institute, Albert Einstein College of Medicine, Bronx, New York, 10461, USA

    Amalio Telenti & William R. Jacobs Jr.

  3. Section of Molecular Pathobiology, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Srinand Sreevatsan, Kathryn E. Stockbauer & James M. Musser

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Telenti, A., Philipp, W., Sreevatsan, S. et al. The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med 3, 567–570 (1997). https://doi.org/10.1038/nm0597-567

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