Role of OxyS of Mycobacterium tuberculosis in oxidative stress: overexpression confers increased sensitivity to organic hydroperoxides.
Mycobacterial genomics has uncovered a novel regulatory gene, oxyS, belonging to the LysR family. There is extensive similarity in the DNA-binding domain of OxyS with that of OxyR, the oxidative stress response protein of many bacteria. Since the oxyR gene of Mycobacterium tuberculosis has been multiply inactivated during evolution it was conceivable that some of its functions could be effected by OxyS. It is shown here that OxyS is produced at low levels and that there are at least three different oxyS alleles present in clinical isolates of M. tuberculosis that are susceptible or resistant to isoniazid. Overproduction or depletion of OxyS did not affect susceptibility to isoniazid but increasing the concentration of the regulator lowered levels of the alkyl hydroperoxide reductase, AhpC, and rendered the tubercle bacillus more susceptible to organic hydroperoxides.
Domenech
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Unité de génétique moléculaire bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.
Honoré
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Heym
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Cole
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D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology*; D054464:Peroxiredoxins; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010545:Peroxides; D012097:Repressor Proteins; D014157:Transcription Factors; D010544:Peroxidases; D054464:Peroxiredoxins; C076136:catalase HPI; D007538:Isoniazid