title: Mutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Mallika
authors.initials: M
authors.lastname: Lavania
authors.forename: Abu
authors.initials: A
authors.lastname: Hena
authors.forename: Hasanoor
authors.initials: H
authors.lastname: Reja
authors.forename: Astha
authors.initials: A
authors.lastname: Nigam
authors.forename: Nibir Kumar
authors.initials: NK
authors.lastname: Biswas
authors.forename: Itu
authors.initials: I
authors.lastname: Singh
authors.forename: Ravindra P
authors.initials: RP
authors.lastname: Turankar
authors.forename: Ud
authors.initials: U
authors.lastname: Gupta
authors.forename: Senthil
authors.initials: S
authors.lastname: Kumar
authors.forename: Latika
authors.initials: L
authors.lastname: Rewaria
authors.forename: Pradip K R
authors.initials: PK
authors.lastname: Patra
authors.forename: Utpal
authors.initials: U
authors.lastname: Sengupta
authors.forename: Basudeb
authors.initials: B
authors.lastname: Bhattacharya
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001681:Biological Assay; D004269:DNA, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D007917:Leprostatic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007917:Leprostatic Agents; D012293:Rifampin