01759nas a2200253   4500000000100000008004100001260001300042653001200055653003100067653001100098653002300109653001200132653003200144653002500176100001500201700001700216245004800233856005900281300001000340490001300350050003200363520109600395022001401491       2000                            d  c2000 Dec10aDapsone10aDrug Resistance, Microbial10aHumans10aLeprostatic Agents10aleprosy10aMicrobial Sensitivity Tests10aMycobacterium leprae1 aGillis T P1 aWilliams D L00aDapsone resistance in Mycobacterium leprae.  uhttp://leprev.ilsl.br/pdfs/2000/v71s1/pdf/v71s1a19.pdf  aS91-50 v71 Suppl  aInfolep Library - available3 a<p>The folP1 gene of Mycobacterium leprae, which encodes dihydropteroate synthase (DHPS), was studied for the presence of mutations associated with resistance to dapsone (DDS). When the folP1 of several DDS-resistant clinical isolates of M. leprae were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting isoleucine for threonine in DHPS-1, and a second mutation occurred in codon 55, substituting arginine for proline. DNA sequencing of strains of M. leprae resistant to 0.01 g% DDS in the mouse diet revealed that 13 of 14 strains contained either the 53 or 55 folP1 mutation. None of the susceptible strains and only one of five strains resistant to 0.001 g% DDS revealed a mutation in folP1, suggesting that only high-level DDS resistance is associated with the mutations identified in folP1. Development and application of simple molecular tests to assess drug-related mutations in M. leprae could establish current levels of drug resistance in leprosy as a reference point for future monitoring of drug resistance at the global level.</p>  a0305-7518