Characterization of mutations conferring streptomycin resistance to multidrug-resistant Mycobacterium tuberculosis isolates from Myanmar
Characterization of mutations conferring streptomycin resistance to multidrug-resistant Mycobacterium tuberculosis isolates from Myanmar
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DOI：
10.1016/j.tube.2018.05.003
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发表时间：
2018-07-01
期刊：
影响因子：
3.2
通讯作者：
Suzuki, Yasuhiko
中科院分区：
文献类型：
--
作者：
Oo, Nan Aye Thida;San, Lai Lai;Suzuki, Yasuhiko
大量研究报告称，rpsL（编码S12蛋白）、rrs（编码16S rRNA）和gidB（编码rRNA甲基转移酶）的突变导致对链霉素（STR）产生耐药性，链霉素在缅甸通常用于耐多药结核病（MDR-TB）治疗和再治疗。本研究的目的是探讨缅甸141株耐药耐药耐药结核分离株中rpsL、rrs和gidB的变异和突变频率。多数分离株属于北京基因型（105株，74.5%）。69.5%（98/141）的耐药菌株存在rpsL突变，其中以Lys43Arg突变最为普遍（92.0%,90/98），且与北京基因型显著相关（P < 0.001）。在16.3%（23/141）的分离株中发现15种不同的gidB突变，其中大多数为新突变。此外，根据我们的研究结果，我们建议gidB中的A276C核苷酸取代作为缅甸北京家族的系统发育标记。rpsL、rrs和gidB序列分析的敏感性为83.7%，较好地预测了缅甸分离株的STR耐药性。然而，16.3%（23/141）的分离株没有检测到突变基因。因此，强烈建议进一步研究阐明其他可能的耐药机制。目前的发现可能有助于开发分子STR敏感性测定，从而有助于在缅甸开发结核病治疗和控制策略。
Numerous studies report that mutations of rpsL (encoding the S12 protein), rrs (encoding 16S rRNA) and gidB (encoding rRNA methyltransferase) are responsible for conferring resistance to streptomycin (STR), which is usually used in both multidrug-resistant tuberculosis (MDR-TB) treatments and re-treatments in Myanmar. The aim of this study was to explore the variation and frequency of mutations in rpsL, rrs and gidB in 141 STR-resistant MDR-TB isolates from Myanmar. Most isolates belonged to the Beijing genotype (105, 74.5%). Moreover, mutations in rpsL were identified in 69.5% (98/141) of the STR-resistant isolates, where the most prevalent (92.0%, 90/98) and significantly associated mutation with the Beijing genotype (P < 0.001) was Lys43Arg. Fifteen different mutations in gidB were found in 16.3% (23/141) of the isolates, and most of them were novel mutations. Moreover, based on our results, we suggest A276C nucleotide substitution in gidB as a phylogenetic marker for the Beijing family in Myanmar. Sequence analysis of rpsL, rrs and gidB with a sensitivity of 83.7% satisfactorily predicted STR resistance in Myanmar isolates. However, in 16.3% (23/141) of the isolates, none of the examined genes showed mutation. Hence, further studies are strongly recommended to elucidate other possible resistance mechanisms. The present findings may be useful in developing molecular STR susceptibility assays, which in turn could contribute to develop TB treatments and control strategies in Myanmar.