Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
Department of Mycobacteriology, Laboratory Division, National Tuberculosis Institute, Bengaluru, Karnataka, India.
Int J Mycobacteriol. 2020 Apr-Jun;9(2):212-215. doi: 10.4103/ijmy.ijmy_30_20.
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.
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 × DR-TB culture specimens were included. All specimens were evaluated for genetic analysis using predesigned primers of atpE and Rv0678 genes.
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.
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.
atpE 基因突变或转录阻遏子 Rv0678 基因突变分别与三磷酸腺苷合酶抑制和外排泵上调有关，可能导致体外对贝达喹啉的耐药性。这是印度首例研究与这种新型药物相关的突变。
2019 年（1 月至 6 月），共纳入 68 例实验室确诊的耐多药结核病（XDR-TB）（氟喹诺酮耐药[n=52]和二线注射剂耐药[n=12]）和 4×DR-TB 培养标本。所有标本均采用预先设计的 atpE 和 Rv0678 基因引物进行基因分析。
在耐多药结核病（XDR-TB）分离株（n=64）中，未发现 atpE 或 Rv0678 基因的突变。然而，在 XDR-TB 分离株（n=4）中，有 1 个标本（25%）与 atpE 基因 49 位的突变有关，导致亮氨酸被脯氨酸取代（L-49-P）。Rv0678 基因未观察到突变。
本研究显示，仅有四分之一的 XDR-TB 分离株的 atpE 基因突变；Rv0678 基因未发现其他突变。据我们所知，atpE 基因中的这种新型突变（L-49-P）在印度北部首次报道。
