Unissa A Nusrath, Selvakumar N, Narayanan Sujatha, Suganthi C, Hanna L E
Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (NIRT), Indian Council of Medical Research (ICMR), No. 1 Mayor Sathyamoorthy Road, Chetput, Chennai, Tamil Nadu 600 031, India.
Biomed Res Int. 2015;2015:257983. doi: 10.1155/2015/257983. Epub 2015 Jan 28.
Mutation at codon 315 of katG gene is the major cause for isoniazid (INH) resistance in Mycobacterium tuberculosis (M. tuberculosis). Substitution at codon 315 of katG gene was analyzed in 85 phenotypically resistant isolates collected from various parts of southern India by direct sequencing method. The obtained results were interpreted in the context of minimum inhibitory concentration (MIC) of INH. Of the 85 phenotypically resistant isolates, 56 (66%) were also correlated by the presence of resistance mutations in the katG gene; 47 of these isolates had ACC, 6 had AAC, 2 had ATC, and one had CGC codon. The frequency of Ser315 substitution in katG gene was found to be higher (70%) amongst multidrug-resistant (MDR) strains than among non-MDR (61%) INH-resistant isolates. Further, the frequency of mutations was found to be greater (74%) in isolates with higher MIC values in contrast to those isolates with low MIC values (58%). Therefore, the study identified high prevalence of Ser315Thr substitution in katG gene of INH-resistant isolates from south India. Also, isolates harboring this substitution were found to be associated with multidrug and high level INH resistance.
katG基因第315位密码子突变是结核分枝杆菌对异烟肼（INH）耐药的主要原因。采用直接测序法对从印度南部不同地区收集的85株表型耐药菌株的katG基因第315位密码子的替换情况进行了分析。所得结果结合INH的最低抑菌浓度（MIC）进行解读。在85株表型耐药菌株中，有56株（66%）也与katG基因中耐药突变的存在相关；其中47株为ACC密码子，6株为AAC密码子，2株为ATC密码子，1株为CGC密码子。发现katG基因中Ser315替换的频率在耐多药（MDR）菌株中（70%）高于非MDR耐INH菌株（61%）。此外，与低MIC值的菌株（58%）相比，高MIC值的菌株中突变频率更高（74%）。因此，该研究确定了印度南部耐INH菌株的katG基因中Ser315Thr替换的高流行率。此外，发现携带这种替换的菌株与耐多药和高水平INH耐药相关。
