THE EXTREME SENSITIVITY OF MYCOBACTERIUM-TUBERCULOSIS TO THE FRONT-LINE ANTITUBERCULOSIS DRUG ISONIAZID

Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolo g of the central regulator of peroxide stress response in enteric bact eria, Inactivation of oxyR is specific for M. tuberculosis and other m embers of the M. tuberculosis complex, This phenomenon appears as a pa radox due to the ability of this organism to parasitize host macrophag es, in which the ingested organisms are likely to be exposed to reacti ve oxygen intermediates, However, the surprising finding that M. tuber culosis has multiple deletions, nonsense and frameshift mutations in o xyR may help explain the exceptionally high sensitivity of M. tubercul osis to the potent antituberculosis agent isoniazid. One of the genes affected by oxyR lesions, ahpC (encoding an alkylhydroperoxide reducta se) may determine the intrinsic sensitivity of mycobacteria to isoniaz id.