ACTIVE EFFLUX AS A MECHANISM OF RESISTANCE TO CIPROFLOXACIN IN STREPTOCOCCUS-PNEUMONIAE

The accumulation of fluoroquinolones (FQs) was studied in a FQ-suscept ible laboratory strain of Streptococcus pneumoniae (strain R6). Uptake of FQs was not saturable, was rapidly reversible, and appeared to occ ur by passive diffusion. In the presence of glucose, which energizes b acteria, the uptake of FQs decreased. Inhibitors of the proton motive force and ATP synthesis increased the uptake of FQs in previously ener gized bacteria. Similar results were observed with the various FQs tes ted and may be explained to be a consequence simply of the pH gradient that exists across the cytoplasmic membrane. From a clinical suscepti ble strain (strain SPn5907) we isolated in vitro on ciprofloxacin an F Q-resistant mutant (strain SPn5929) for which the MICs of hydrophilic molecules were greater than those of hydrophobic molecules, and the mu tant,vas resistant to acriflavine, cetrimide, and ethidium bromide. St rain SPn5929 showed a significantly decreased uptake of ciprofloxacin, and its determinant of resistance to ciprofloxacin was transferred by transformation to susceptible laboratory strain R6 (strain R6tr5929). No mutations in the quinolone resistance-determining regions of the g yrA and parC genes were found. In the presence of arsenate or carbonyl cyanide m-chlorophenylhydrazone, the levels of uptake of ciprofloxaci n by the two resistant strains, SPn5929 and R6tr5929, reached the leve ls of uptake of their susceptible parents. These results suggest an ac tive efflux of ciprofloxacin in strain SPn5929.