Theresa Wilson1, Desmond M. Collins1
1AgResearch, Wallaceville Animal Research Centre, PO Box 40063, Upper Hutt, New Zealand
Tóm tắt
A gene conferring low‐level isoniazid (INH) resistance on Mycobacterium smegmatis was isolated from a cosmid library of the genome of an INH‐resistant Mycobacterium bovis strain. The gene had good homology with ahpC, the product of which is a subunit of alkyl hydroperoxide reductase, and also with a family of thiol‐specific antioxidant enzymes. A mutation was found in the promoter upon comparison with the equivalent DNA sequence from the INH‐sensitive parent strain. Promoter sequences from other INH‐sensitive and INH‐resistant M. bovis and Mycobacterium tuberculosis strains were sequenced and the mutation was found only in the INH‐resistant strains. An INH‐resistant M. tuberculosis strain also had an additional mutation in the promoter region. The wild‐type promoter and promoters with one and two mutations were ligated into a reporter plasmid containing the lacZ gene. The presence of the first mutation resulted in a sixfold induction of β‐galactosidase activity, and the presence of both mutations caused a 10‐fold induction. Increased expression of AhpC may account for some of the INH resistance of strains of the M. tuberculosis complex.
