Molecular characterization of multidrug-resistant isolates of Mycobacterium tuberculosis from patients in North India
Molecular characterization of multidrug-resistant isolates of Mycobacterium tuberculosis from patients in North India
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DOI：
10.1128/aac.46.2.443-450.2002
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发表时间：
2002-02-01
影响因子：
4.9
通讯作者：
Hasnain, SE
中科院分区：
文献类型：
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作者：
Siddiqi, N;Shamim, M;Hasnain, SE
世界卫生组织已将印度确定为结核分枝杆菌感染的主要热点地区。我们对来自印度的126株结核分枝杆菌临床分离株中与多药耐药相关的基因座序列进行了特征分析，以确定各自的突变。选择了rpoB(利福平)、katG和inh.4核糖体结合位点(异烟肼)、gyrA和gyrB(氧氟沙星)和rpsL和RRS(链霉素)。我们在这些基因座上发现了已知和新的突变。很少有rpoB基因突变与结核分枝杆菌分离株表现出的耐药水平相关，并且发生频率与先前报道的不同。密码子526至531的错义突变似乎是导致对利福平高度耐药的关键因素。我们在katG基因座上发现了一个常见的Arg463Leu替换，以及一些新的插入和缺失。Inh.4基因的核糖体结合部位也发生了突变。在对氧氟沙星耐药的菌株中观察到的最常见的突变是gyrA基因中的Ser95Thr替换。少数几个分离株在该基因座上显示出其他突变。7株链霉素耐药菌株在第121位赖氨酸残基发生沉默突变。虽然某些突变广泛存在，表明这些基因座的多态程度很大，但其他突变并不常见，这表明该地区流行的耐多药结核分枝杆菌菌株存在多样性。我们的研究结果还对多药耐药检测方法的发展具有指导意义，对未来临床治疗方案和药物设计策略的制定也有重要意义。
The World health Organization has identified India as a major hot-spot region for Mycobacterium tuberculosis infection. We have characterized the sequences of the loci associated with multidrug resistance in 126 clinical isolates of M. tuberculosis from India to identify the respective mutations. The loci selected were rpoB (rifampin), katG and the ribosomal binding site of inh.4 (isoniazid), gyrA and gyrB (ofloxacin), and rpsL and rrs (streptomycin). We found known as well as novel mutations at these loci. Few of the mutations at the rpoB locus could be correlated with the drug resistance levels exhibited by the M. tuberculosis isolates and occurred with frequencies different from those reported earlier. Missense mutations at codons 526 to 531 seemed to be crucial in conferring a high degree of resistance to rifampin. We identified a common Arg463Leu substitution in the katG locus and certain novel insertions and deletions. Mutations were also mapped in the ribosomal binding site of the inh.4 gene. A Ser95Thr substitution in the gyrA locus was the most common mutation observed in ofloxacin-resistant isolates. A few isolates showed other mutations in this locus. Seven streptomycin-resistant isolates had a silent mutation at the lysine residue at position 121. While certain mutations are widely present, pointing to the magnitude of the polymorphisms at these loci, others are not common, suggesting diversity in the multidrug-resistant M. tuberculosis strains prevalent in this region. Our results additionally have implications for the development of methods for multidrug resistance detection and are also relevant in the shaping of future clinical treatment regimens and drug design strategies.