Quinoline Derivatives as Promising Inhibitors of Antibiotic Efflux Pump in Multidrug Resistant Enterobacter Aerogenes Isolates

Abdallah      Mahamoud; Jacqueline      Chevalier; Anne      Davin-Regli; Jacques      Barbe; Jean-Marie      Pages

Abstract

Efflux pumps protect the bacterial cell by expelling toxic compounds before they reach intracellular targets. Because this mechanism actively contributes to the resistance of a given bacterium to more than one class of antibiotics, molecules that are able to block the relevant efflux pump are of potential significance to combat drug resistance caused by efflux pumps. Different quinoline derivatives including alkoxy, alkylamino, thioalkoxy and chloroquinolines have been previously reported to make Enterobacter aerogenes resistant isolates that over express the mechanism of efflux, noticeably more susceptible to structurally unrelated antibiotics. In addition, various quinoline derivatives significantly increase the intracellular concentration of chloramphenicol as reported with other inhibitors, thereby suggesting the inhibition of the drug transport by AcrAB-TolC pump, which is fully active in the clinicaly resistant isolates investigated. Here, we discuss the respective properties of this molecular family, taking into account the recent insights into the structural data of AcrB pump.

Keywords: Antibiotic resistance, CCCP (carbonyl cyanide m-chlorophenylhydrazone), quinoline derivatives, Drug efflux, pump, Efflux pump inhibitors, Enterobacter aerogenes, PAβN (phenylalanine arginine β-naphthylamide)