title: Dapsone resistance does not appear to be associated with a mutation in the dihydropteroate synthase-2 gene of Mycobacterium leprae.
abstract: Evidence suggests that resistance to dapsone (DDS) in Mycobacterium leprae is related to the enzyme dihydropteroate synthase (DHPS). Two M. leprae genes (folP-1 and folP-2) encoding DHPS-1 and DHPS-2, respectively, have been identified through the M. leprae genome project. We have studied DDS-susceptible and resistant strains of M. leprae to determine whether the DDS-resistant phenotype is associated with a mutation(s) in folP-2 and to establish the number of genomic copies of the gene encoding DHPS-2 (folP-2). RFLP analysis of genomic DNA from DDS-susceptible and resistant strains of M. leprae exhibited a unique 4.2 kb restriction fragment consistent with a single genomic copy of folP-2 in both phenotypes. DNA encoding folP-2 was amplified by PCR and sequenced from two susceptible and two resistant strains of M. leprae. The folP-2 sequences from these strains were identical indicating that resistance to DDS was not associated with mutation(s) in the gene encoding DHPS-2.
authors.affiliation: Molecular Biology Research Department, GW Long Hansen's Disease Centre, School of Veterinary Medicine, Louisiana State University, Baton Rouge, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Gillis
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004269:DNA, Bacterial / Q000032:analysis; D003622:Dapsone / Q000494:pharmacology*; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D007917:Leprostatic Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009166:Mycobacterium leprae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D007917:Leprostatic Agents; D003622:Dapsone; D004094:Dihydropteroate Synthase