Mutations in the Catalase-Peroxidase Gene from Isoniazid-Resistant Mycobacterium tuberculosis Isolates

Authors:
  • JMJohanna Marostenmaki
    Johanna Marostenmaki
  • AWAlfred Wong
    Alfred Wong
  • MFMark FitzGerald
    Mark FitzGerald
  • WBWilliam A. Black
    William A. Black
  • JSJohn A. Smith
    John A. Smith
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Abstract
Isoniazid resistance in Mycobacterium tuberculosis has been associated with total deletion of the katG gene, which codes for catalase-peroxidase production. To determine whether this is a common mechanism of drug resistance, 9 isolates of isoniazid-resistant and 1 of isoniazid-sensitive M. tuberculosis were analyzed by polymerase chain reaction amplification of a 237-bp sequence of the katG gene. Amplification was observed in the isoniazid-sensitive isolate and in 8 resistant isolates; in only 1 isoniazid-resistant isolate was there no amplification of the expected band, suggesting gene deletion. DNA sequencing showed that 8 of the 9 isolates had point mutations, deletions, or insertions of 1–3 bases. Evidence corroborating the presence of mutations in the katG gene was obtained by single-strand conformation polymorphism analysis in these 8 isolates. Thus, mutations as well as insertions and deletions in the katG gene can account for inactive catalase peroxidase, leading to isoniazid resistance; gene deletion occurs only infrequently, in ∼11% of cases.