A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus.
Fluoroquinolones such as ciprofloxacin and ofloxacin are potent antimicrobial agents that antagonize the A subunit of DNA gyrase. We selected and mapped a novel fluoroquinolone resistance gene on the Staphylococcus aureus chromosome. Resistant mutants were selected with ciprofloxacin or ofloxacin and were uniformly localized to the A fragment of chromosomal DNA digested with SmaI and arrayed by pulsed-field gel electrophoresis. Several mutants (cfxB, ofxC) were genetically mapped between the thr and trp loci in the A fragment. A majority of A fragment fluoroquinolone resistance mutations were associated with reduced susceptibility to novobiocin, an antagonist of the B subunit of DNA gyrase. Two genes previously associated with fluoroquinolone resistance, the gyrA gene of DNA gyrase and the norA gene (associated with decreased drug accumulation), were localized to the G and D fragments, respectively. Thus, the fluoroquinolone resistance mutations in the A fragment are distinct from previously identified fluoroquinolone resistance mutations in gyrA and norA. Whether mutations in the A fragment after a second topoisomerase or another gene controlling supercoiling or affect drug permeation is unknown.
Trucksis
M
M
Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Wolfson
J S
JS
Hooper
D C
DC
D000890:Anti-Infective Agents / Q000494:pharmacology*; D015139:Blotting, Southern; D002874:Chromosome Mapping; D004269:DNA, Bacterial / Q000235:genetics; D004352:Drug Resistance, Microbial; D004587:Electrophoresis, Agar Gel; D005798:Genes, Bacterial; D008040:Genetic Linkage; D008970:Molecular Weight; D009154:Mutation; D015363:Quinolones / Q000494:pharmacology*; D015183:Restriction Mapping; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D015363:Quinolones