Rapid Identification Of A Point Mutation Of The Mycobacterium tuberculosis Catalase-Peroxidase (katG) Gene Associated With Isoniazid Resistance

Authors:
  • JUJames R. Uhl
    James R. Uhl
  • ZTZelalem Temesgen
    Zelalem Temesgen
  • YZYing Zhang
    Ying Zhang
  • LSLeslie Stockman
    Leslie Stockman
  • GRGlenn D. Roberts
    Glenn D. Roberts
  • DWDiana L. Williams
    Diana L. Williams
  • BKBruce C. Kline
    Bruce C. Kline
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Abstract
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 µg/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 µg/mL had mutations affecting codon 463. Restriction analysis of 43 strains with isoniazid MICs ⩽5? 1.0 µg/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 µg/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 ⩽5? 1.0 µg/mL.