Mutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin.

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TitleMutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin.
Publication TypeJournal Article
AuthorsLavania M, Hena A, Reja H, Nigam A, Biswas NK, Singh I, Turankar RP, Gupta U, Kumar S, Rewaria L, Patra PKR, Sengupta U, Bhattacharya B
Abbrev. JournalLepr Rev
JournalLeprosy review
Year of Publication2016
Volume87
Issue1
Pagination93-100
Publication Languageeng
KeywordsAdult, Amino Acid Sequence, Animals, Bacterial Proteins, Biological Assay, DNA, Bacterial, Gene Expression Regulation, Bacterial, Humans, Leprostatic Agents, Male, Mice, Mice, Inbred BALB C, Mutation, Mycobacterium leprae, Polymerase Chain Reaction, Rifampin, Young Adult
Abstract

BACKGROUND: Rifampicin is the major drug in the treatment of leprosy. The rifampicin resistance of Mycobacterium leprae results from a mutation in the rpoB gene, encoding the β subunit of RNA polymerase. As M. leprae is a non-cultivable organism observation of its growth using mouse food-pad (MFP) is the only Gold Standard assay used for confirmation of "in-vivo" drug resistance.

OBJECTIVE: Any mutation at molecular level has to be verified by MFP assay for final confirmation of drug resistance in leprosy.

MATERIAL AND METHODS: In the present study, M. leprae strains showing a mutation only at codon 442 Gln-His and along with mutation either at codon 424 Val-Gly or at 438 Gln-Val within the Rifampicin Resistance Determining Region (RRDR) confirmed by DNA sequencing and by high resolution melting (HRM) analysis were subjected for its growth in MFP.

RESULT AND CONCLUSION: The M. leprae strain having the new mutation at codon 442 Gln-His was found to be sensitive to all the three drugs and strains having additional mutations at 424 Val-Gly and 438 Gln-Val were conferring resistance with Multi drug therapy (MDT) in MFP. These results indicate that MFP is the gold standard method for confirming the mutations detected by molecular techniques.

PubMed URL

http://www.ncbi.nlm.nih.gov/pubmed/27255062?dopt=Abstract

Link to full texthttps://www.lepra.org.uk/platforms/lepra/files/lr/Mar16/15-0039.pdf