RNA Polymerase Inhibitors with Activity against Rifampin-Resistant Mutants of Staphylococcus aureus

A collection of rifampin-resistant mutants of Staphylococcus aureus with characterized RNA polymerase β-subunit (rpoB) gene mutations was cross-screened against a number of other RNA polymerase inhibitors to correlate susceptibility with specific rpoB genotypes. The rpoB mutants were cross-resistant to streptolydigin and sorangicin A. In contrast, thiolutin, holomycin, corallopyronin A, and ripostatin A retained activity against the rpoB mutants. The second group of inhibitors may be of interest as drug development candidates.