title: Rapid identification of a point mutation of the Mycobacterium tuberculosis catalase-peroxidase (katG) gene associated with isoniazid resistance.
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 > 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.
authors.affiliation: Division of Clinical Microbiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
authors.forename: F R
authors.initials: FR
authors.lastname: Cockerill
authors.forename: J R
authors.initials: JR
authors.lastname: Uhl
authors.forename: Z
authors.initials: Z
authors.lastname: Temesgen
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Stockman
authors.forename: G D
authors.initials: GD
authors.lastname: Roberts
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
authors.forename: B C
authors.initials: BC
authors.lastname: Kline
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D010544:Peroxidases; D002374:Catalase; C076136:catalase HPI; D007538:Isoniazid