Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates.
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.
Malléa
Monique
M
EA2197, IFR48, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
Mahamoud
Abdallah
A
Chevalier
Jacqueline
J
Alibert-Franco
Sandrine
S
Brouant
Pierre
P
Barbe
Jacques
J
Pagès
Jean-Marie
JM
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*
D000634:Aminoquinolines; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D002701:Chloramphenicol