Back to Journals » Infection and Drug Resistance » Volume 11

Enriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains

Authors Lavania M, Singh I, Turankar RP, Gupta AK, Ahuja M, Pathak V, Sengupta U

Received 19 September 2017

Accepted for publication 13 November 2017

Published 25 January 2018 Volume 2018:11 Pages 169—175

DOI https://doi.org/10.2147/IDR.S152082

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Joachim Wink


Mallika Lavania,1 Itu Singh,1 Ravindra P Turankar,1 Anuj Kumar Gupta,2 Madhvi Ahuja,1 Vinay Pathak,1 Utpal Sengupta1

1Stanley Browne Laboratory, The Leprosy Mission Trust India, TLM Community Hospital Nand Nagari, 2Agilent Technologies India Pvt Ltd, Jasola District Centre, New Delhi, India

Abstract: Despite more than three decades of multidrug therapy (MDT), leprosy remains a major public health issue in several endemic countries, including India. The emergence of drug resistance in Mycobacterium leprae (M. leprae) is a cause of concern and poses a threat to the leprosy-control program, which might ultimately dampen the achievement of the elimination program of the country. Rifampicin resistance in clinical strains of M. leprae are supposed to arise from harboring bacterial strains with mutations in the 81-bp rifampicin resistance determining region (RRDR) of the rpoB gene. However, complete dynamics of rifampicin resistance are not explained only by this mutation in leprosy strains. To understand the role of other compensatory mutations and transmission dynamics of drug-resistant leprosy, a genome-wide sequencing of 11 M. leprae strains – comprising five rifampicin-resistant strains, five sensitive strains, and one reference strain – was done in this study. We observed the presence of compensatory mutations in two rifampicin-resistant strains in rpoC and mmpL7 genes, along with rpoB, that may additionally be responsible for conferring resistance in those strains. Our findings support the role for compensatory mutation(s) in RNA polymerase gene(s), resulting in rifampicin resistance in relapsed leprosy patients.

Keywords: leprosy, rifampicin resistance, compensatory mutations, next generation sequencing, relapsed, MDT, India

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]