Mechanisms of fluoroquinolone resistance in Staphylococcus aureus.
Fluoroquinolone resistance that arose in the test strain during ciprofloxacin therapy of experimental Staphylococcus aureus endocarditis was studied. In two isolates, resistance was due to a decreased sensitivity of the process of DNA synthesis to fluoroquinolones, suggesting the presence of an altered DNA gyrase. Another isolate had an enhanced energy-dependent mechanism, possibly an efflux system, by which cell-associated [3H]norfloxacin was reduced. When a 2.7-kb SphI-KpnI chromosomal fragment from this organism was cloned into pUC19, fluoroquinolone resistance was expressed in an Escherichia coli host, and such organisms acquired an energy-dependent ability to reduce cell-associated [3H]norfloxacin. Lack of homology between this DNA and other cloned gyrA genes indicated that its protein products are distinct from the gyrA protein. S. aureus has the capability of decreasing the quantity of cell-associated fluoroquinolone. An enhancement of this system by an as yet undefined mechanism and an alteration in DNA gyrase are two means by which this organism can develop resistance to fluoroquinolones.
Kaatz
G W
GW
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan.
Seo
S M
SM
Ruble
C A
CA
D000667:Ampicillin / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000032:analysis; D002939:Ciprofloxacin / Q000494:pharmacology; D003001:Cloning, Molecular; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004269:DNA, Bacterial / Q000096:biosynthesis; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D009154:Mutation; D009643:Norfloxacin / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D011815:R Factors; D015183:Restriction Mapping; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; D002939:Ciprofloxacin; D000667:Ampicillin; D004250:DNA Topoisomerases, Type II; D009643:Norfloxacin