Mutations in the catalase-peroxidase gene from isoniazid-resistant Mycobacterium tuberculosis isolates.
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 approximately 11% of cases.
Altamirano
M
M
Department of Pathology, University of British Columbia, Vancouver, Canada.
Marostenmaki
J
J
Wong
A
A
FitzGerald
M
M
Black
W A
WA
Smith
J A
JA
D001426:Bacterial Proteins; D001483:Base Sequence; D002374:Catalase / Q000235:genetics*; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial / Q000235:genetics; D005798:Genes, Bacterial; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D010544:Peroxidases / Q000235:genetics*; D016133:Polymerase Chain Reaction
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010544:Peroxidases; D002374:Catalase; C076136:catalase HPI; D007538:Isoniazid