Growth of Staphylococcus aureus in the presence of salicylate leads to reduced ciprofloxacin and ethidium accumulation and increased resistance to ethidium. Salicylate induced reduction in ciprofloxacin accumulation is energy-independent while salicylate induced alterations in ethidium accumulation and efflux is proton motive force-dependent. NorA is an intrinsic multidrug efflux pump that contributes to intrinsic levels of fluoroquinolone and ethidium resistance in S. aureus. The NorA inhibitor reserpine did not dramatically affect the ability of salicylate to induce increased ciprofloxacin and ethidium resistance. Inactivation of norA did not alter the ability of salicylate to induce increased ciprofloxacin and ethidium resistance levels and a reduction in ciprofloxacin accumulation. These data demonstrate that NorA is not absolutely required for the salicylate-inducible multidrug resistance mechanism of S. aureus.
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