title: New pyridoquinoline derivatives as potential inhibitors of the fluoroquinolone efflux pump in resistant Enterobacter aerogenes strains.
abstract: Enterobacter aerogenes, one of the most frequently isolated nosocomial pathogens in France, is exhibiting increasing multidrug resistance mechanisms associated with a change in membrane permeability. For drugs of the quinolone family, mutations in the target and active efflux play a prominent role in the resistance. We report here the effect of several pyridoquinoline derivatives that restore a noticeable fluoroquinolone accumulation to resistant strains that overexpress the MarA activator. Studies of the energy-dependent quinolone efflux indicate that the most efficient derivatives tested probably inhibit the resistance process by acting as substrate competitors on the pump extruding intracellular norfloxacin.
authors.affiliation: CJF9606-EA2197, Faculté de Médecine, Université de la Méditerranée, 13385 Marseille, Cedex 05, France.
authors.forename: J
authors.initials: J
authors.lastname: Chevalier
authors.forename: S
authors.initials: S
authors.lastname: Atifi
authors.forename: A
authors.initials: A
authors.lastname: Eyraud
authors.forename: A
authors.initials: A
authors.lastname: Mahamoud
authors.forename: J
authors.initials: J
authors.lastname: Barbe
authors.forename: J M
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004336:Drug Antagonism; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D021902:Enterobacter aerogenes / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C080002:MarA protein, E coli; D011804:Quinolines; D009643:Norfloxacin