title: Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates.
abstract: Over the last decade, MDR (multidrug resistance) has increased worldwide in microbial pathogens by efflux mechanisms, leading to treatment failures in human infections. Several Gram-negative bacteria efflux pumps have been described. These proteinaceous channels are capable of expelling structurally different drugs across the envelope and conferring antibiotic resistance in various bacterial pathogens. Combating antibiotic resistance is an urgency and the blocking of efflux pumps is an attractive response to the emergence of MDR phenotypes in infectious bacteria. In the present study, various alkylaminoquinolines were tested as potential inhibitors of drug transporters. We showed that alkylaminoquinolines are capable of restoring susceptibilities to structurally unrelated antibiotics in clinical isolates of MDR Gram-negative bacteria. Antibiotic efflux studies indicated that 7-nitro-8-methyl-4-[2'-(piperidino)ethyl]aminoquinoline acts as an inhibitor of the AcrAB-TolC efflux pump and restores a high level of intracellular drug concentration. Inhibitory activity of this alkylaminoquinoline is observed on clinical isolates showing different resistance phenotypes.
authors.affiliation: EA2197, IFR48, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Malléa
authors.forename: Abdallah
authors.initials: A
authors.lastname: Mahamoud
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alibert-Franco
authors.forename: Pierre
authors.initials: P
authors.lastname: Brouant
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbe
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002701:Chloramphenicol / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D021902:Enterobacter aerogenes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000634:Aminoquinolines; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D002701:Chloramphenicol