Abstract:
:The exceptional sensitivity of Mycobacterium tuberculosis to isonicotinic acid hydrazide (INH) lacks satisfactory definition. M. tuberculosis is a natural mutant in oxyR, a central regulator of peroxide stress response. The ahpC gene, which encodes a critical subunit of alkyl hydroperoxide reductase, is one of the targets usually controlled by oxyR in bacteria. Unlike in mycobacterial species less susceptible to INH, the expression of ahpC was below detection limits at the protein level in INH-sensitive M. tuberculosis and Mycobacterium bovis strains. In contrast, AhpC was detected in several series of isogenic INH-resistant (INHr) derivatives. In a demonstration of the critical role of ahpC in sensitivity to INH, insertional inactivation of ahpC on the chromosome of Mycobacterium smegmatis, a species naturally insensitive to INH, dramatically increased its susceptibility to this compound. These findings suggest that AhpC counteracts the action of INH and that the levels of its expression may govern the intrinsic susceptibility of mycobacteria to this front-line antituberculosis drug.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhang Y,Dhandayuthapani S,Deretic Vdoi
10.1073/pnas.93.23.13212subject
Has Abstractpub_date
1996-11-12 00:00:00pages
13212-6issue
23eissn
0027-8424issn
1091-6490journal_volume
93pub_type
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