Mutation Analysis of theMycobacterium leprae folP1Gene and Dapsone Resistance

Abstract

ABSTRACTDiaminodiphenylsulfone (dapsone) has long been used as a first-line drug worldwide for the treatment of leprosy. Diagnosis for dapsone resistance ofMycobacterium lepraeby DNA tests would be of great clinical value, but the relationship between the nucleotide substitutions and susceptibility to dapsone must be clarified before use. In this study, we constructed recombinant strains of cultivableMycobacterium smegmatiscarrying theM. leprae folP1gene with or without a point mutation, disrupting their ownfolPgene on the chromosome. Dapsone susceptibilities of the recombinant bacteria were measured to examine influence of the mutations. Dapsone MICs for most of the strains with mutations at codon 53 or 55 ofM. leprae folP1were 2 to 16 times as high as the MIC for the strain with the wild-typefolP1sequence, but mutations that changed Thr to Ser at codon 53 showed somewhat lower MIC values than the wild-type sequence. Strains with mutations at codon 48 or 54 showed levels of susceptibility to dapsone comparable to the susceptibility of the strain with the wild-type sequence. This study confirmed that point mutations at codon 53 or 55 of theM. leprae folP1gene result in dapsone resistance.