Nature Medicine
3, 567 - 570 (1997)
doi:10.1038/nm0597-567
The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutolAmalio Telenti1, 2, 4, Wolfgang J. Philipp1, Srinand Sreevatsan3, Claudia Bernasconi1, Kathryn E. Stockbauer3, Brigitte Wieles1, James M. Musser3
& William R. Jacobs Jr.2
1Institute for Medical Microbiology, University of Bern, 3010 Bern, Switzerland
2Department of Microbiology and Immunology and Howard Hughes Medical Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461, USA
3Section of Molecular Pathobiology, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
4Correspondence should be addressed to A.T. 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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