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1Department of Microbiology and Immunologyl, Howard Hughes Medical Institute, and Department of Biochemistry
2Albert Einstein College of Medicine, Bronx, NY 10461, USA
1 Author for correspondence: William R. Jacobs, Jr. Tel: + 1 718 430 2888. Fax: + 1 718 518 0366.e-mail: jacobs@aecom.yu.edu
ABSTRACT
SUMMARY: A target of the anti-tuberculosis drugs isoniazid (INH) and ethionamide (ETH) has been shown to be an enoyl reductase, encoded by the inhA gene. The mabA (mycolic acid biosynthesis A) gene is located immediately upstream of inhA in Mycobacterium tuberculosis, Mycobacterium bo wis and Mycobacterium smegmatis. The MabA protein from M. tuberculosis was expressed in Escherichia coli and shown to have 3-ketoacyl reductase activity, consistent with a role in mycolic acid biosynthesis. In M. smegmatis, inhA and mabA are independently transcribed, but in M. tuberculosis and M. bowis BCG, mabA and inhA constitute a single operon. Several INH-ETH-resistant M. tuberculosis clinical isolates contain point mutations in the ribosome-binding site of mabA in the mabA-inhA operon. However, genetic dissection of this operon reveals that the INH-ETH-resistance phenotype is encoded only by hhA, and not by mabA.
Present address: Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, NY 10021, USA.
Present address: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
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