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

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TitleEnriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains.
Publication TypeJournal Article
AuthorsLavania M, Singh I, Turankar RP, Gupta AK, Ahuja M, Pathak V, Sengupta U
Abbrev. JournalInfect Drug Resist
JournalInfection and drug resistance
Year of Publication2018
Volume11
Pagination169-175
Publication Languageeng
KeywordsCompensatory mutations, India, Leprosy, MDT, Next generation sequencing, relapsed, Rifampicin resistance
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.

PubMed URL

http://www.ncbi.nlm.nih.gov/pubmed/29416362?dopt=Abstract

DOI10.2147/IDR.S152082
Download PDFhttps://www.dovepress.com/getfile.php?fileID=40285
PubMed Central IDPMC5790067