Ciprofloxacin, salicylate, and 2,4-dinitrophenol decrease production of AmpC-type β-lactamase in two Citrobacter freundii clinical isolates

Abstract

The effect of ciprofloxacin and two marPAB inducers on the susceptibility to beta-lactam antibiotics in two AmpC beta-lactamase semiconstitutive producer Citrobacter freundii clinical isolates (the DM1 and DM2 strains) was studied. Possible changes in outer membrane protein expression, permeability to cephaloridine, active efflux, and hydrolytic activity of beta-lactamase-crude extracts were evaluated under the influence of ciprofloxacin, sodium salicylate, and 2,4-dinitrophenol. Results were compared with those of the effect of the same three chemicals on a normally beta-lactamase-inducible wild-type C. freundii strain. The three assayed compounds decreased beta-lactamase hydrolysis on cephaloridine in both the two clinical isolates as well as in the wild-type strain. However, only the DM1 and DM2 strains showed increased susceptibility to beta-lactams. Sodium salicylate and 2,4-dinitrophenol, but not ciprofloxacin, reduced the expression of a 45-kDa outer membrane protein in the three studied strains, which was accompanied by a 4- to 20-fold diminution in permeability to cephaloridine. In conclusion, two marRAB inducers and ciprofloxacin induced the Mar phenotype and repressed AmpC beta-lactamase synthesis in the DM1 and DM2 clinical isolates.