ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex.

Abstract:

: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 beta-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.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Wilson TM,Collins DM

doi

10.1046/j.1365-2958.1996.449980.x

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

1025-34

issue

5

eissn

0950-382X

issn

1365-2958

journal_volume

19

pub_type

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