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Mutation in atpE and Rv0678 genes associated with bedaquline resistance among drug-resistant tuberculosis patients: A pilot study from a high-burden setting in Northern India

机译:ATPE和RV0678基因的突变与耐药结核病患者的Bedaquline抗性相关:印度北部高负担环境的试验研究

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Background: Mutations in atpE gene or transcriptional repressor Rv0678 gene associated with inhibition of adenosine 5 '-triphosphate synthase and upregulation of efflux pumps, respectively, may potentially lead to in vitro resistance to bedaquiline. This is the first study from India, which looks at mutations associated with this novel drug. Methods: In 2019 (January to June), a total of 68 laboratory-confirmed pre-extensively drug-resistant tuberculosis (XDR-TB) (fluoroquinolone resistant [n = 52] and second-line injectables resistant [n = 12]) and 4 x DR-TB culture specimens were included. All specimens were evaluated for genetic analysis using predesigned primers of atpE and Rv0678 genes. Results: Among the pre-XDR-TB isolates (n = 64), there were no mutations found in either atpE or Rv0678. However, among the XDR-TB isolates (n = 4), one specimen (25%) was found to be associated with a mutation in atpE gene at position 49, resulting in the amino acid leucine replaced by proline (L-49-P). No mutations were observed with the Rv0678 gene. Conclusion: In this study, genetic analysis showed that only one-fourth XDR-TB isolates had a mutation in the atpE gene; there were no other mutations found in the Rv0678 gene. To the best of our knowledge, this novel mutation (L-49-P) in atpE gene is being reported for the first time in northern India.
机译:背景:分别与腺苷5' - 三磷酸三磷酸三磷酸合酶的抑制相关的ATPE基因或转录抑制的RV0678基因的突变可能导致对床奎石的体外抗性。这是印度的第一次研究,它看起来与这种新药相关的突变。方法:2019年(1月至6月),共有68例实验室确认的预抗药性结核(XDR-TB)(氟代喹啉酮抗性[N = 52]和抗性[n = 12])和4×DR-TB培养标本包括在内。使用ATPE和RV0678基因的预测引物评估所有标本进行遗传分析。结果:在XDR-TB预分离物(n = 64)中,ATPE或RV0678中没有发现突变。然而,在XDR-TB分离物(n = 4)中,发现一个样本(25%)与ATPE基因的突变在49处与ATPE基因的突变相关联,导致脯氨酸替代的氨基酸亮氨酸(L-49-P. )。用RV0678基因没有观察到突变。结论:在本研究中,遗传分析表明,只有四分之一XDR-TB分离物在ATPE基因中突变; RV0678基因中没有发现其他突变。据我们所知,在印度北部首次报道ATPE基因中的这种新型突变(L-49-P)。

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