1] School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China [2] Department of Medical Microbiology and Parasitology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
J Antibiot (Tokyo). 2014 Apr;67(4):291-7. doi: 10.1038/ja.2013.133. Epub 2013 Dec 11.
Rifampicin (RIF) and isoniazid (INH) Mycobacterium tuberculosis isolates were characterized from south-central China and transmission patterns within the Beijing genotype were detected in multidrug-resistant isolates. Six genetic regions, including rpoB for RIF, and katG, inhA, ahpC, mabA-inhA promoter and oxyR-ahpC intergenic region for INH were analyzed by DNA sequencing in 60 multidrug-resistant isolates, including 7 extensively drug-resistant isolates. The genomic deletion RD105 was characterized by genotyping. The results showed that 91.7% of MDR isolates carried mutations in the rpoB gene and 85.0% of the MDR isolates had at least one mutation in the INH resistance-associated loci detected. In total, these six genetic regions are responsible for 95.0% of MDR isolates. Mutations in the XDR isolates were focused on rpoB 531 or rpoB 526, and katG 315, correlating to a higher frequency level of resistance to RIF MIC ⩾8 μg ml⁻¹ and INH MIC ⩾4 μg m⁻¹. Three novel katG mutants (G273S, I266T and P232S) and three new alleles (E458A, S509R and P535S) in the rpoB gene were identified. Among the 85 clinical isolates, 78 are Beijing genotypes and the other 7 are non-Beijing genotypes. The results present the identification of genetic markers in M. tuberculosis isolates, some of which may be unique to this particular geographic niche. An understanding of the mutations in these drug-resistant strains may aid in choosing the appropriate chemotherapy regimens on the pharmacogenetic properties of the mutations for the prevention and control of tuberculosis.
从中国中南部分离的利福平（RIF）和异烟肼（INH）结核分枝杆菌分离株，并在耐多药分离株中检测到北京基因型内的传播模式。对 60 株耐多药分离株（包括 7 株广泛耐药分离株）进行 DNA 测序，分析了包括 rpoB 基因（用于 RIF）和 katG、inhA、ahpC、mabA-inhA 启动子和 oxyR-ahpC 基因间隔区在内的 6 个遗传区域。通过基因分型鉴定了 RD105 基因组缺失。结果显示，91.7%的耐多药分离株 rpoB 基因发生突变，85.0%的耐多药分离株 INH 耐药相关基因座至少发生 1 个突变。总的来说，这 6 个遗传区域占耐多药分离株的 95.0%。XDR 分离株的突变主要集中在 rpoB531 或 rpoB526 和 katG315，与更高频率的 RIF MIC ⩾8μg/ml⁻¹和 INH MIC ⩾4μg/ml⁻¹耐药相关。鉴定出 rpoB 基因中的 3 种新 katG 突变体（G273S、I266T 和 P232S）和 3 种新等位基因（E458A、S509R 和 P535S）。在 85 株临床分离株中，78 株为北京基因型，其余 7 株为非北京基因型。这些结果表明，在结核分枝杆菌分离株中鉴定出了遗传标记，其中一些可能是该特定地理小生境所特有的。了解这些耐药株的突变可能有助于根据突变的药物遗传学特性选择适当的化疗方案，以预防和控制结核病。
