RIFAMPICIN RESISTANCE AND MUTATION OF THE RPOB GENE IN MYCOBACTERIUM-TUBERCULOSIS

Using 39 clinical isolates of Mycobacterium tuberculosis strains with a broad range of susceptibility to rifampicin, we examined the relatio nship between the degree of resistance to rifampicin and mutational si tes of the rpoB gene. All rifampicin-resistant strains had missense mu tations. Twenty strains (95%) had a mutation in the cluster I region, which has also been reported in Escherichia coli [Jin and Gross (1988) J. Mol. Biol. 202, 45-58], and the remaining one strain had a mutatio n at codon 381 [Ala-->Val] in the N-terminal region, which has not bee n reported in E. coli. Among 18 rifampicin-susceptible strains, two ha d a mutation in the cluster I region and the other three strains had a mutation in the cluster In region. The mutations at codons 513 (5%), 526 (33%) or 531 (43%) in the cluster I region led to high level resis tance to rifampicin (50 mu g ml(-1)less than or equal to MIC). The mut ations at the other sites, in the cluster III region (codons 679 or 68 7) and even in the cluster I region (codon 514, 521, or 533), showed l ow level (MIG = 12.5 mu g ml(-1)) or no (MIC < 0.39 mu g ml(-1)) resis tance to rifampicin. These results suggest that mutations in the rpoB gene are, mostly, but not necessarily, associated with rifampicin resi stance of M. tuberculosis, and the sites of mutations on the rpoB gene will affect the level of resistance to rifampicin.