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

In this study eight different mutations identified in an 81 bp section of a "hot spot" region of the rpoB gene of RMP resistant Mycobacterium tuberculosis clinical 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. Gene rpoB carrying mutations in codon 513 (Q/L) introduced into an M. tuberculosis laboratory 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.Mutations in an 81 bp "hot spot" region of the rpoB of M. tuberculosis lead to different levels of resistance to rifampin. Some mutations in this "hot spot" region of rpoB require a specific genetic background for the host strain to develop resistance to rifampin. Therefore, the identification of such mutations in a clinical M. tuberculosis strain is not enough to classify the given strain as resistant to rifampin.Tuberculosis (TB) is a devastating infectious disease causing high mortality and morbidity worldwide with 8 million new TB cases and 2–3 million deaths annually. The situation of TB is made even worse by the rising emergence of drug resistant strains of Mycobacterium tuberculosis. Multi-drug resistant TB (MDR-TB) is defined as resistant to at least isoniazid (INH) and rifampin (RMP), the two most active first-line drugs against TB. MDR-TB treatment takes up to 2 years with second line drugs, which are expensive and have side effects. In 2006 US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) drew attention to the emergence of M. tuberculosis with extensive drug resistance to second-line antituberculosis drugs (XDR). XDR-TB is resistant to at least INH and RMP among the first