RAPID IDENTIFICATION OF A POINT MUTATION OF THE MYCOBACTERIUM-TUBERCULOSIS CATALASE-PEROXIDASE (KATG) GENE ASSOCIATED WITH ISONIAZID RESISTANCE

The complete catalase-peroxidase (katG) gene DNA sequence was determin ed for 15 strains of Mycobacterium tuberculosis with a wide range of s usceptibility to isoniazid. Five of 9 strains with isoniazid MICs grea ter than or equal to 1.0 mu g/mL had one or more missense mutations an d all 5 strains had a common G --> T transversion in codon 463, causin g the replacement of arginine with leucine and the loss of an NciI or MspI restriction site. None of 6 strains with an isoniazid MIC <1.0 mu g/mL had mutations affecting codon 463. Restriction analysis of 43 st rains with isoniazid MICs greater than or equal to 1.0 mu g/mL showed that 19 (44.2%) had lost the NciI-MspI restriction site at the locus o f codon 463 while only 1 of 32 strains with isoniazid MICs less than o r equal to 1.0 mu g/mL had this restriction polymorphism. These result s indicate that the mutation arginine --> leucine in codon 463 of the catalase-peroxidase gene occurs in a significant fraction (44.2%) of M . tuberculosis strains with isoniazid MICs greater than or equal to 1. 0 mu g/mL.