Genetic evaluation of relationship between mutations in rpoB and resistance of Mycobacterium tuberculosis to rifampin

BMC Microbiology - Tập 9 Số 1 - 2009
Anna Żaczek1, Anna Brzostek1, Ewa Augustynowicz‐Kopeć2, Zofia Zwolska2, Jarosław Dziadek1
1Institute for Medical Biology, Polish Academy of Sciences, Lodz, Poland
2Department of Microbiology, National Research Institute of Tuberculosis and Lung Diseases, Warsaw, Poland

Tóm tắt

AbstractBackgroundRifampin is a first line antituberculosis drug active against bacilli in logarithmic and stationary phase, which interferes with RNA synthesis by binding to bacterial RNA polymerase. Tubercle bacilli achieve resistance to rifampin by accumulation of mutations in a short-81 bp region of therpoBgene. Among many mutations identified in therpoB gene, few were verified by molecular genetic methods as responsible for resistance to rifampin (RMP).ResultsIn this study eight different mutations identified in an 81 bp section of a "hot spot" region of therpoB gene of RMP resistantMycobacterium tuberculosisclinical strains were evaluated in respect to drug resistance. It was found that: mutations in positions 526 (H/D), 516 (D/V) and 531 (S/L) result in high level resistance to rifampin; mutations in positions 516 (D/Y), 515 (M/I), 510 (Q/H) or a double mutation in codons 512 (S/I) and 516 (D/G) relate to low level of resistance. GenerpoB carrying mutations in codon 513 (Q/L) introduced into anM. tuberculosislaboratory strain did not cause resistance to rifampin, however the same gene introduced into two different clinical strains did, with the level of resistance depending on the host strain.ConclusionMutations in an 81 bp "hot spot" region of therpoBofM. tuberculosislead to different levels of resistance to rifampin. Some mutations in this "hot spot" region ofrpoBrequire a specific genetic background for the host strain to develop resistance to rifampin. Therefore, the identification of such mutations in a clinicalM. tuberculosisstrain is not enough to classify the given strain as resistant to rifampin.

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