Significance of ahpC promoter mutations for the prediction of isoniazid resistance in Mycobacterium tuberculosis.
To determine the value of ahpC promoter mutations for the rapid prediction of isoniazid resistance, this genomic region was characterized in 50 isoniazid-resistant and 12 isoniazid-sensitive Mycobacterium tuberculosis isolates. Of the resistant isolates, 12 had ahpC promoter mutations, but only one possessed both an ahpC promoter mutation and a katG codon 315 substitution, although the latter was found in the majority (54%) of the isoniazid-resistant isolates investigated. This investigation presents empirical evidence that the central portion of the ahpC promoter is the most valuable genetic locus to complement katG codon 315 characterizations in order to increase the sensitivity of molecular tests for the prediction of isoniazid resistance.
Department of Infectious Diseases and Tropical Medicine, Klinikum Innenstadt, University of Munich, Germany.
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H
Rinder
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A
Thomschke
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Rüsch-Gerdes
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G
Bretzel
K
K
Feldmann
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Rifai
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T
Löscher
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D001483:Base Sequence; D003062:Codon; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics*; D010544:Peroxidases; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D004269:DNA, Bacterial; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; C076136:catalase HPI; D007538:Isoniazid