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 determined for 15 strains of Mycobacterium tuberculosis with a wide range of susceptibility to isoniazid. Five of 9 strains with isoniazid MICs ≥5?1.0 �g/mL had one or more missense mutations and all 5 strains had a common G - T transversion in codon 463, causing the replacement of arginine with leucine and the loss of an Nci I or Msp I restriction site. None of 6 strains with an isoniazid MIC < 1.0 �g/mL had mutations affecting codon 463. Restriction analysis of 43 strains with isoniazid MICs <1.0 �g/mL showed that 19 (44.2%) had lost the Nci I-Msp I restriction site at the locus of codon 463 while only 1 of 32 strains with isoniazid MICs ≥1.0 �g/mL had this restriction polymorphism. These results 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 ≥1.0 �g/mL.