MOLECULAR MECHANISM OF ACTION OF THE ANTIBIOTIC RIFAMPICIN

The lopophilic antibiotic rifampicin is successfully used in the treatment of tuberculosis. On the molecular level it interferes with the metabolism of Eubacteria by blocking RNA synthesis. This effect is the consequence of the tight binding of the drug to a single and highly specific binding site on the DNA-dependent RNA polymerase. The enzyme-bound drug strongly inhibits RNA chain initiation and chain elongation. This inhibition can be explained by the influence of enzyme-bound rifampicin on binding sites for the reaction products diphosphate and RNA. In order to reach its target the antibiotic must penetrate into the cytoplasm of the bacteria. Mutants have been discovered which are resistant to rifampicin because its uptake from the medium is significantly reduced.