Induction of fibronectin-binding proteins and increased adhesion of quinolone-resistant Staphylococcus aureus by subinhibitory levels of ciprofloxacin

We recently reported that strain EN1252a, a fluoroquinolone-resistant deriv ative of Staphylococcus aureus NCTC8325 with mutations in grlA and gyrA, ex pressed increased levels of fibronectin-binding proteins (FnBPs) and showed a significantly higher attachment to fibronectin-coated polymer surfaces a fter growth in the presence of subinhibitory concentrations of ciprofloxaci n. The present study evaluated the occurrence and frequency of fluoroquinol one-induced FnBP-mediated adhesion in clinical isolates of fluoroquinolone- resistant methicillin-resistant S. aureus (MRSA) and methicillin-susceptibl e S. aureus (MSSA). Eight of ten MRSA isolates and four of six MSSA isolate s with grlA and gyrA mutations exhibited significant increases in attachmen t to fibronectin-coated surfaces after growth in the presence of one-quarte r the MIC of ciprofloxacin. Fluoroquinolone-induced FnBP-mediated adhesion of one clinical MRSA strain and the double mutant strain EN1252a also occur red on coverslips removed from the subcutaneous space of guinea pigs. For s train EN1252a, the regulation of fnb transcription by sub-MICs of ciproflox acin was studied on reporter plasmids carrying fnb-luxAB fusions. One-quart er of the MIC of ciprofloxacin significantly increased fnbB, hut not fnbA, promoter activity of the fluoroquinolone-resistant mutant but not its fluor oquinolone-susceptible parent ISP794. This response was abolished by pretre atment with rifampin, indicating an effect at the level of transcription. A ctivation of the fnbB promoter was not due to an indirect effect of ciprofl oxacin on growth rate and still occurred in an agr mutant of strain EN1252a . These data suggest that sub-MIC levels of ciprofloxacin activate the fnbB promoter of some laboratory and clinical isolates, thus contributing to in creased production of FnBP(s) and leading to higher levels of bacterial att achment to fibronectin-coated or subcutaneously implanted coverslips.