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 beta-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.
O'Neill
A
A
Antimicrobial Research Centre and Division of Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Oliva
B
B
Storey
C
C
Hoyle
A
A
Fishwick
C
C
Chopra
I
I
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004352:Drug Resistance, Microbial; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007769:Lactams; D007783:Lactones / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011760:Pyrrolidinones / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D004791:Enzyme Inhibitors; D007769:Lactams; D007783:Lactones; D011760:Pyrrolidinones; C096600:ripostatin A; C006361:acetopyrrothine; C015265:holomycin; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin