在吉尔吉斯斯坦的耐利福平及异烟肼结核分枝杆菌中 rpoB、katG、inhA 和 ahp 基因突变。
Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic.
机构信息
Institute of Molecular Biology and Medicine, 3 Togolok Moldo street, 720040, Bishkek, Kyrgyzstan.
School of Public Health, Al-Farabi Kazakh National University, Al-Farabi avenue 71, Almaty, Kazakhstan, 050040.
出版信息
BMC Microbiol. 2018 Mar 22;18(1):22. doi: 10.1186/s12866-018-1168-x.
BACKGROUND
The aim of this study was to identify mutations of rpoB, katG, inhA and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium tuberculosis susceptibility to RIF and INH using culture method of absolute concentrations, and commercially available test named "TB-BIOCHIP" (Biochip-IMB, Moscow, Russian Federation).
RESULTS
For RIF-resistance, TB-BIOCHIP's sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and 90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533 (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 > Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315→Thr (88.6%) was the most prevalent mutation leading to resistance to INH.
CONCLUSIONS
In Kyrgyz Republic, the most prevalent mutation in RIF-resistant strains was Ser531 → Leu in rpoB gene, as opposed to Ser315 → Thr in katG gene in INH-resistant Mycobacterium tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium tuberculosis were strains with combined mutations Ser531 → Leu in rpoB gene and Ser315 → Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the advantage of obtaining results in only two days.
背景
本研究旨在鉴定与吉尔吉斯斯坦结核分枝杆菌对利福平（RIF）和异烟肼（INH）耐药相关的 rpoB、katG、inhA 和 ahp-基因的突变。我们研究了 633 份来自原发性肺结核（TB）患者的涂片样本。我们使用绝对浓度培养方法和名为“TB-BIOCHIP”（Biochip-IMB，莫斯科，俄罗斯联邦）的商业可用测试来验证结核分枝杆菌对 RIF 和 INH 的敏感性。
结果
对于 RIF 耐药性，TB-BIOCHIP 的灵敏度和特异性分别为 88%和 97%，对于 INH 耐药性分别为 84%和 95%，对于多药耐药（MDR）分别为 90%和 97%。在 RIF 耐药株中，TB-BIOCHIP 显示 rpoB 基因密码子 531（64.8%）、526（17.3%）、516（8.1%）、511（5.4%）、533（3.2%）、522（0.6%）和 513（0.6%）的突变。最常见的是 Ser531>Leu 突变（63.7%）。导致 INH 耐药的突变中，91.2%发生在 katG 基因，7%发生在 inhA 基因，1.8%发生在 ahpC 基因。导致 INH 耐药的最常见突变是 Ser315→Thr（88.6%）。
结论
在吉尔吉斯斯坦，RIF 耐药株最常见的突变是 rpoB 基因中的 Ser531→Leu，而 INH 耐药结核分枝杆菌中的 katG 基因是 Ser315→Thr。在吉尔吉斯斯坦，MDR 结核分枝杆菌的主要储存库是 rpoB 基因中 Ser531→Leu 与 katG 基因中 Ser315→Thr 联合突变的菌株。TB-BIOCHIP 的灵敏度中等，但优势在于仅需两天即可获得结果。
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