Genetic analysis of Staphylococcus aureus RNA polymerase mutants.
Spontaneous mutants of Staphylococcus aureus resistant to rifampin, rifamycin SV, streptovaricin, or streptolydigin were isolated and shown to be resistant due to chromosomal rather than plasmid mutations. Based on data concerning spontaneous mutation rates, genetic cotransduction rates, and in vitro sensitivity studies, four major antibiotic cross-resistance patterns were found. The genetic markers responsible for these cross-resistance patterns were shown to be separable by transduction. Nonpurified RNA polymerase activity in lysates of mutants showed the same sensitivity to these antibiotics as shown by the mutants on solid media. A model is proposed explaining possible structure-function relationships involved in the binding of these antibiotics to the RNA polymerase molecule and the mutations resulting in resistance to these antibiotics. This model includes generally overlapping but different-sized binding sites on the RNA polymerase protein coded for by similarly arranged mutable sites on the DNA.
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D005796:Genes; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology; D012294:Rifamycins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D013310:Streptovaricin / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012294:Rifamycins; D013310:Streptovaricin; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin