Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo, 001-0020, Japan.
German Nepal Tuberculosis Project c/o Nepal Anti-Tuberculosis Association, Kalimati, Kathmandu, Post Box 1494, Nepal.
Tuberculosis (Edinb). 2020 Dec;125:101985. doi: 10.1016/j.tube.2020.101985. Epub 2020 Aug 8.
Mutation in rpsL (encoding ribosomal protein S12), rrs (encoding 16S ribosomal RNA) and gidB (encoding 7-methylguanosine methyltransferase) are associated with resistance to streptomycin (STR), which is used for the treatment of multi-drug resistant tuberculosis (MDR-TB) in Nepal. The aim of our study is to analyze the correlation between mutations in the target genes and STR-resistance in 197 Mycobacterium tuberculosis (MTB) isolates from Nepal. Mutations in rpsL was harbored by 65.9% of isolates, in which the most common mutation in rpsL is caused by K43R (58.8%) and were significantly associated with Beijing genotype (P < 0.001). About 13.2% of isolates harbored mutations in two highly mutable regions of rrs, the 530 loop and the 912 region. About 13.2% of gidB mutants do not show any mutation in rpsL and rrs, which might suggest the role of gidB mutations in STR-resistance in MTB. In addition, 5.6% of isolates do not show any mutations in three genes examined, suggesting the involvement of other mechanism in STR-resistance in MTB. Our findings can be implemented for the establishment of molecular STR-susceptibility testing, in which tuberculosis can be treated with appropriate drugs and can improve control strategies for DR-TB.
rpsL（编码核糖体蛋白 S12）、rrs（编码 16S 核糖体 RNA）和 gidB（编码 7-甲基鸟苷甲基转移酶）的突变与链霉素（STR）耐药性相关，STR 用于治疗尼泊尔的耐多药结核病（MDR-TB）。我们的研究目的是分析目标基因中的突变与来自尼泊尔的 197 株结核分枝杆菌（MTB）分离株的 STR 耐药性之间的相关性。rpsL 突变存在于 65.9%的分离株中，其中 rpsL 最常见的突变是由 K43R 引起的（58.8%），与北京基因型显著相关（P<0.001）。大约 13.2%的分离株携带 rrs 的两个高度易变区域 530 环和 912 区的突变。大约 13.2%的 gidB 突变体在 rpsL 和 rrs 中没有显示任何突变，这可能表明 gidB 突变在 MTB 的 STR 耐药性中起作用。此外，5.6%的分离株在三个检测的基因中没有显示任何突变，这表明 MTB 的 STR 耐药性可能涉及其他机制。我们的发现可以用于建立分子 STR 药敏检测，从而可以用适当的药物治疗结核病，并改善耐多药结核病的控制策略。
