The extreme sensitivity of Mycobacterium tuberculosis to the front-line antituberculosis drug isoniazid.

Abstract:

:Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolog of the central regulator of peroxide stress response in enteric bacteria. Inactivation of oxyR is specific for M. tuberculosis and other members of the M. tuberculosis complex. This phenomenon appears as a paradox due to the ability of this organism to parasitize host macrophages, in which the ingested organisms are likely to be exposed to reactive oxygen intermediates. However, the surprising finding that M. tuberculosis has multiple deletions, nonsense and frameshift mutations in oxyR may help explain the exceptionally high sensitivity of M. tuberculosis to the potent antituberculosis agent isoniazid. One of the genes affected by oxyR lesions, ahpC (encoding an alkylhydroperoxide reductase) may determine the intrinsic sensitivity of mycobacteria to isoniazid.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Deretic V,Pagán-Ramos E,Zhang Y,Dhandayuthapani S,Via LE

doi

10.1038/nbt1196-1557

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

1557-61

issue

11

eissn

1087-0156

issn

1546-1696

journal_volume

14

pub_type

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