Hillemann D, Kubica T, Agzamova R, Venera B, Rüsch-Gerdes S, Niemann S
National Reference Center for Mycobacteria, Forschungszentrum Borstel, Borstel, Germany.
Int J Tuberc Lung Dis. 2005 Oct;9(10):1161-7.
To analyse possible associations of specific mutations conferring rifampicin (RMP) and isoniazid (INH) resistance with Beijing and non Beijing genotype strains of Mycobacterium tuberculosis from Kazakhstan.
Genotypic analysis of 92 multidrug-resistant (MDR), 50 INH but not RMP-resistant (INHr/RMPs) and 10 fully susceptible strains of M. tuberculosis from Kazakhstan was performed. In the MDR group, 59 strains (64.1%), and within the INHr/RMPs group, 32 strains (64.0%) were classified as Beijing genotype.
Analysis of the rpoB gene of the MDR strains revealed 10 different mutations in five codons, with rpoB codons 531 (65.2%), 526 (23.9%) and 516 (7.6%) most frequently affected. A significantly higher proportion of the rpoB S531L mutation was found among Beijing genotype strains compared with non Beijing strains (71.2% vs. 46.2%, P = 0.027). All 92 MDR isolates (100%), irrespective of their genotype, carried a mutation in codon 315 of the katG gene (S315T). However, in the INHr/RMPS control group, the S315T mutation was significantly more prevalent in the Beijing than in the non Beijing group (96.9% vs. 71.4%, P = 0.012).
The high similarity of mutations supports the assumption that transmission of resistant strains is a major reason for the emergence of drug resistance in this region.
分析赋予利福平（RMP）和异烟肼（INH）耐药性的特定突变与来自哈萨克斯坦的结核分枝杆菌北京基因型和非北京基因型菌株之间可能存在的关联。
对来自哈萨克斯坦的92株耐多药（MDR）、50株仅耐INH但不耐RMP（INHr/RMPs）以及10株完全敏感的结核分枝杆菌菌株进行基因分型分析。在MDR组中，59株（64.1%），在INHr/RMPs组中，32株（64.0%）被归类为北京基因型。
对MDR菌株的rpoB基因分析显示，在五个密码子中有10种不同突变，其中rpoB密码子531（65.2%）、526（23.9%）和516（7.6%）受影响最为频繁。与非北京基因型菌株相比，北京基因型菌株中rpoB S531L突变的比例显著更高（71.2%对46.2%，P = 0.027）。所有92株MDR分离株（100%），无论其基因型如何，katG基因密码子315均发生突变（S315T）。然而，在INHr/RMPS对照组中，S315T突变在北京基因型组中比非北京基因型组更为普遍（96.9%对71.4%，P = 0.012）。
突变的高度相似性支持了以下假设，即耐药菌株的传播是该地区耐药性出现的主要原因。
