000151312 001__ 151312
000151312 005__ 20181203021959.0
000151312 0247_ $$2doi$$a10.1111/j.1365-2958.1995.mmi_17050889.x
000151312 022__ $$a0950-382X
000151312 02470 $$2PMID$$a8596438
000151312 037__ $$aARTICLE
000151312 245__ $$aMycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid
000151312 260__ $$c1995
000151312 269__ $$a1995
000151312 336__ $$aJournal Articles
000151312 520__ $$aThe systems participating in detoxification of reactive oxygen intermediates in Mycobacterium tuberculosis are believed to play a dual role in the biology of this highly adapted human pathogen: (i) they may contribute to the survival of this bacterium in the host; and (ii) alterations in the gene encoding catalase/peroxidase have been linked to this organism's resistance to the front-line antituberculosis drug isoniazid. These relationships prompted us to extend investigations of the oxidative-stress-response systems in M. tuberculosis by analysing the alkyl hydroperoxide reductase gene ahpC and its putative regulator oxyR. Surprisingly, the oxyR gene was found to be inactivated by multiple lesions in M. tuberculosis H37Rv. These alterations were observed in all M. tuberculosis strains tested, and in members of the M. tuberculosis complex: Mycobacterium bovis BCG, Mycobacterium africanum, and Mycobacterium microti. The corresponding region carrying these genes in Mycobacterium leprae, an organism not sensitive to isoniazid, has a complete oxyR gene divergently transcribed from ahpC. An increase in minimal inhibitory concentration for isoniazid was observed upon transformation of M. tuberculosis H37Rv with cosmids carrying the oxyR-ahpC region of M. leprae. In keeping with the observed inactivation of oxyR, transcriptional activity of the corresponding region in M. tuberculosis was an order of magnitude lower than that of the oxyR gene from M. leprae. While the loss of this putative regulator of oxidative-stress response in M. tuberculosis is paradoxical considering the fact that survival in host macrophages is regarded as a critical feature of this pathogen, it offers a partial explanation for the exquisite sensitivity of M. tuberculosis to isoniazid.
000151312 6531_ $$aDNA-Binding Proteins
000151312 6531_ $$aGenes
000151312 6531_ $$aBacterial
000151312 6531_ $$aGenes
000151312 6531_ $$aRegulator
000151312 6531_ $$aMutation
000151312 700__ $$aDeretic, V
000151312 700__ $$aPhilipp, W
000151312 700__ $$aDhandayuthapani, S
000151312 700__ $$aMudd, M H
000151312 700__ $$aCurcic, R
000151312 700__ $$aGarbe, T
000151312 700__ $$aHeym, B
000151312 700__ $$aVia, L E
000151312 700__ $$0243892$$aCole, S T$$g177247
000151312 773__ $$j17$$k5$$q889-900$$tMolecular microbiology
000151312 909C0 $$0252302$$pUPCOL$$xU11742
000151312 909CO $$ooai:infoscience.tind.io:151312$$pSV$$particle
000151312 917Z8 $$x148230
000151312 917Z8 $$x148230
000151312 937__ $$aEPFL-ARTICLE-151312
000151312 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000151312 980__ $$aARTICLE