Inhibitors of antibiotic efflux in resistant Enterobacter aerogenes and Klebsiella pneumoniae strains

Abstract

In Enterobacter aerogenes and Klebsiella pneumoniae, efflux provides efficient extrusion of antibiotics and contributes to the multidrug resistance phenotype. One of the alkoxyquinoline derivatives studied here, 2,8-dimethyl-4-(2'-pyrrolidinoethyl)-oxyquinoline, restores noticeable drug susceptibility to resistant clinical strains. Analyses of energy-dependent chloramphenicol efflux indicate that this compound inhibits the efflux pump mechanism and improves the activity of structurally unrelated antibiotics on multidrug-resistant E. aerogenes and K. pneumoniae isolates.

FIG. 1.

Effect of compound 905 on chloramphenicol accumulation in E. aerogenes EA27. Exponential-phase bacteria in Luria-Bertani broth were removed, resuspended in sodium phosphate buffer, and incubated with radiolabeled chloramphenicol for various times (15, 22). Intracellular accumulations were followed in the absence (+) or presence of compound 905 (□) or PAβN (▵) at 0.1 mM. Values (expressed as counts per minute/optical density [cpm/OD]) were obtained from independent duplicate measurements.