Cockerill F R, Uhl J R, Temesgen Z, Zhang Y, Stockman L, Roberts G D, Williams D L, Kline B C
Division of Clinical Microbiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
J Infect Dis. 1995 Jan;171(1):240-5. doi: 10.1093/infdis/171.1.240.
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.
对15株对异烟肼敏感性差异较大的结核分枝杆菌菌株测定了过氧化氢酶-过氧化物酶（katG）基因的完整DNA序列。在9株异烟肼最低抑菌浓度（MIC）≥1.0微克/毫升的菌株中，有5株存在一个或多个错义突变，并且所有这5株菌株在密码子463处都有一个共同的G→T颠换，导致精氨酸被亮氨酸取代，并丢失了一个NciI或MspI限制性酶切位点。6株异烟肼MIC＜1.0微克/毫升的菌株中均没有影响密码子463的突变。对43株异烟肼MIC≥1.0微克/毫升的菌株进行限制性分析显示，19株（44.2%）在密码子463位点处丢失了NciI-MspI限制性酶切位点，而在32株异烟肼MIC≤1.0微克/升的菌株中只有1株有这种限制性多态性。这些结果表明，过氧化氢酶-过氧化物酶基因密码子463处的精氨酸→亮氨酸突变在异烟肼MIC≥1.0微克/毫升的结核分枝杆菌菌株中占相当比例（44.2%）。
