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Year : 2020  |  Volume : 9  |  Issue : 2  |  Page : 212-215

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

1 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Mycobacteriology, Laboratory Division, National Tuberculosis Institute, Bengaluru, Karnataka, India
3 Department of Public Health, RTL, Northern Region, World Health Organization, India
4 Department of Public Health, NPOTB and Laboratories, World Health Organization, India

Correspondence Address:
Manish Soneja
Department of Medicine, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmy.ijmy_30_20

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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 × 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.

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