Mechanisms of Fluoroquinolone Resistance in Staphylococcus aureus

Fluoroquinolone resistance that arose in the test strain during ciproftoxacin 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 ftuoroquinolones, 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]norfioxacin was reduced. When a 2.7-kb SphI-KpnI chromosomal fragment from this organism wasclonedinto pUC19, fluoroquinolone resistance was expressed in an Escherichia coli host, and such organism sacquired an energy dependent ability to reduce cell-associated [3H]norftoxacin. 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.