title: Mutations in the rpoB gene of rifampicin-resistant Mycobacterium tuberculosis strains from Thailand and its evolutionary implication.
abstract: Novel mutations in the rpoB gene are reported for 70 rifampicin-resistant (RIFr) M. tuberculosis strains from Thailand. Sequence analysis of these strains revealed mutations in a 435 base-pair region of the rpoB gene. Twenty-eight strains (40%) had single mutations, and 26 of those strains had mutations at positions never before reported, of which, just one had a substitution at Val-432 (Asp), and the remaining 25, a silent mutation at Gln-517. All other strains had multiple mutations, of which 24 (34%) had mutations at two positions; 9(13%), at three positions; 2(3%), at five positions; and 1(1%) at six positions. Five strains (7%), reported to have the RIFr phenotype, contained no mutation in the examined region of the rpoB gene. Surprisingly, one RIFr strain had silent mutations at 29 positions. By far the dominant mutation was the silent mutations at Gln-517 (86%). This investigation demonstrates that mutations in the rpoB gene of M. tuberculosis strains from Thailand are more varied than previously reported for RIFr M. tuberculosis strains. Screening by means of PCR-SSCP clearly separated RIFr strains from rifampicin-susceptible (RIFs) strains. There was no correlation between RIFr mutations and random amplified polymorphic DNA (RAPD) types.
authors.affiliation: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. tmprt@mahidol.ac.th
authors.forename: Pongrama
authors.initials: P
authors.lastname: Ramasoota
authors.forename: Pannamthip
authors.initials: P
authors.lastname: Pitaksajjakul
authors.forename: Wanchai
authors.initials: W
authors.lastname: Phatihattakorn
authors.forename: Vijittra
authors.initials: V
authors.lastname: Pransujarit
authors.forename: Jirakan
authors.initials: J
authors.lastname: Boonyasopun
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012293:Rifampin / Q000494:pharmacology*; D013785:Thailand
chemical_list: D000904:Antibiotics, Antitubercular; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin