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 > or = 1.0 microgram/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 NciI or MspI restriction site. None of 6 strains with an isoniazid MIC < 1.0 microgram/mL had mutations affecting codon 463. Restriction analysis of 43 strains with isoniazid MICs > or = 1.0 microgram/mL showed that 19 (44.2%) had lost the NciI-MspI restriction site at the locus of codon 463 while only 1 of 32 strains with isoniazid MICs < or = 1.0 microgram/L 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 > or = 1.0 microgram/mL.
Cockerill
F R
FR
Division of Clinical Microbiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Uhl
J R
JR
Temesgen
Z
Z
Zhang
Y
Y
Stockman
L
L
Roberts
G D
GD
Williams
D L
DL
Kline
B C
BC
D001426:Bacterial Proteins; D001483:Base Sequence; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D004352:Drug Resistance, Microbial; D005798:Genes, Bacterial; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D014397:Tuberculosis, Pulmonary / Q000382:microbiology
D001426:Bacterial Proteins; D017931:DNA Primers; D010544:Peroxidases; D002374:Catalase; C076136:catalase HPI; D007538:Isoniazid