Publication Date:
1996-06-14
Description:
Mutations that eliminate KatG catalase-peroxidase activity prevent activation of isoniazid and are a major mechanism of resistance to this principal drug for the treatment of Mycobacterium tuberculosis infections. However, the loss of KatG activity in clinical isolates seemed paradoxical because KatG is considered an important factor for the survival of the organism. Expression of either KatG or the recently identified alkyl hydroperoxidase AhpC was sufficient to protect bacilli against the toxic effects of organic peroxides. To survive during infection, isoniazid-resistant KatG mutants have apparently compensated for the loss of KatG catalase-peroxidase activity by a second mutation, resulting in hyperexpression of AhpC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sherman, D R -- Mdluli, K -- Hickey, M J -- Arain, T M -- Morris, S L -- Barry, C E 3rd -- Stover, C K -- Z01 AI000783-11/Intramural NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1641-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Tuberculosis and Molecular Microbiology, PathoGenesis Corporation, Seattle, Washington 98119, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658136" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Antitubercular Agents/*pharmacology
;
*Bacterial Proteins
;
Base Sequence
;
Cloning, Molecular
;
DNA, Bacterial
;
Drug Resistance, Microbial/genetics
;
Drug Synergism
;
Enzyme Induction
;
Gene Expression Regulation, Bacterial
;
Hydrogen Peroxide/pharmacology
;
Isoniazid/*pharmacology
;
Molecular Sequence Data
;
Mutation
;
Mycobacterium bovis/drug effects/genetics
;
Mycobacterium tuberculosis/*drug effects/*genetics
;
Oxidoreductases/*genetics
;
Peroxidases/biosynthesis/genetics/metabolism
;
Peroxiredoxins
;
Promoter Regions, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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