02166nas a2200289   4500000000100000008004100001653002600042653001300068653003100081653000800112653001200120653001000132653002700142100001400169700001200183700001500195700001300210700001200223700001300235700001500248245015200263856007600415300001200491490000700503520135200510022001401862       2018                            d10aRifampicin resistance10arelapsed10aNext generation sequencing10aMDT10aleprosy10aIndia10aCompensatory mutations1 aLavania M1 aSingh I1 aTurankar R1 aGupta AK1 aAhuja M1 aPathak V1 aSengupta U00aEnriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790067/pdf/idr-11-169.pdf  a169-1750 v113 a<p>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.</p>
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