title: Activity of and development of resistance to corallopyronin A, an inhibitor of RNA polymerase.
abstract: We explored the properties of corallopyronin A (CorA), a poorly characterized inhibitor of bacterial RNA polymerase (RNAP). It displayed a 50% inhibitory concentration of 0.73 μM against RNAP, compared with 11.5 nM for rifampin. The antibacterial activity of CorA was also inferior to rifampin, and resistant mutants of Staphylococcus aureus were easily selected. The mutations conferring resistance resided in the rpoB and rpoC subunits of RNAP. We conclude that CorA is not a promising antibacterial drug candidate.
authors.affiliation: Antimicrobial Research Centre and Institute of Molecular and Cellular Biology, School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Katherine
authors.initials: K
authors.lastname: Mariner
authors.forename: Martin
authors.initials: M
authors.lastname: McPhillie
authors.forename: Rachel
authors.initials: R
authors.lastname: Trowbridge
authors.forename: Catriona
authors.initials: C
authors.lastname: Smith
authors.forename: Alex J
authors.initials: AJ
authors.lastname: O'Neill
authors.forename: Colin W G
authors.initials: CW
authors.lastname: Fishwick
authors.forename: Ian
authors.initials: I
authors.lastname: Chopra
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000235:genetics; D007783:Lactones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007783:Lactones; C532894:corallopyronin A; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin