Characterization of rifampin-resistant isolates of Mycobacterium tuberculosis from Sichuan in China.

Rifampin is a key component of standard short-course first-line therapy against Mycobacterium tuberculosis, and rifampin resistance of this pathogen has been reported to be related to rpoB gene mutations. The objective of this study was to characterize the rpoB gene mutations in rifampin-resistant M. tuberculosis isolates circulated in Sichuan. Sequencing of rpoB gene and spoligotyping were performed on 268 randomly selected isolates from January 2008 to May 2010. The results indicated that 207 (97.2%) rifampin-resistant isolates had mutations at 26 codons in the amplified region with 50 different genotypes, while 1 (1.8%) of 55 susceptible isolates had a nonsense mutation. The most common mutations were in codon 531 (55.9%), 526 (16.4%), 516 (10.3%) and 511 (8.9%). Among the 213 resistant isolates, 150 (70.4%) belonged to the Beijing family and mutation at codon 531 (TCG→TTG) was associated with Beijing genotype (χ(2), 9.8305; p, 0.0017). It is demonstrated that the frequency of 511 (CTG→CCG) mutations in Sichuan was higher than in other provinces of China, as well as other geographic regions worldwide. It is suggested that only a small portion (2.7%) of rifampin-resistant Beijing genotype isolates in Sichuan be spread by clonal expansion during the study period.