J Korean Med Sci.  1997 Apr;12(2):92-98. 10.3346/jkms.1997.12.2.92.

Isoniazid resistance and the point mutation of codon 463 of katG gene of Mycobacterium tuberculosis

• Shim TS
• Yoo CG
• Han SK
• Shim YS
• Kim YW

• KMID: 1079653
• DOI: http://doi.org/10.3346/jkms.1997.12.2.92

Abstract

It has long been known that almost all isoniazid (INH) resistant mycobacteria lose the catalase and peroxidase activities along with reduced or no virulence for guinea pigs. Recently resistance to INH has become known to be associated with mutations of katG gene encoding the HPI (Hydroperoxidase I) type catalase and peroxidase. Among these mutations, the point mutation of codon 463 of katG gene is found frequently, and is suggested as being associated with INH resistance. Therefore we performed this study in order to confirm the correlation between the point mutation of codon 463 of the katG gene and INH resistance of M. tuberculosis in Korea. Fifty isolates, 32 of which were resistant to INH, and 18 of which were sensitive to INH, were selected for this study. We used PCR-SSCP and RFLP analysis to detect the point mutation of the codon 463 of katG gene and confirmed the CGG (arginine) to CTG (leucine) mutation by direct sequencing analysis. Among 32 resistant isolates, 7 isolates (22%) had the same restriction pattern compared with that of the reference strain (H37Rv), and 25 isolates (78%) showed a different restriction pattern. Among 18 sensitive isolates, 7 isolates (39%) had the same restriction pattern compared with that of H37Rv, and 11 isolates (61%) showed a different restriction pattern. These results suggest that the CGG to CTG change of codon 463 of katG gene of M. tuberculosis may be a polymorphism not related with INH resistance.

MeSH Terms

Antitubercular Agents/pharmacology*
Codon*
Deoxyribonuclease HpaII/metabolism
Deoxyribonucleases, Type II Site-Specific/metabolism
Drug Resistance, Microbial/genetics
Human
Isoniazid/pharmacology*
Mycobacterium tuberculosis/genetics
Mycobacterium tuberculosis/enzymology*
Mycobacterium tuberculosis/drug effects
Peroxidases/genetics*
Point Mutation*
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Sequence Analysis, DNA