Rifabutin susceptibility and rpoB gene mutations in multi-drug resistant mycobacterium tuberculosis

Shim, Tae Sun; Kim, Jin Sub; Park, Mi Sun; Lim, Chae Man; Lee, Sang Do; Koh, Youn Suk; Kim, Woo Sung; Kim, Dong Soon; Kim, Won Dong

Abstract

BACKGROUND
Following several decades of decline, the incidence of tuberculosis has recently begun to increase in many countries and the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutaitions of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB.
METHODS
Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients two visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the result were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB.
RESULTS
Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526.
CONCLUSION
The frequency and pattern of mutations of the rpoB gene of Korean MDR-Tb isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.