title: Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective.
abstract: Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed. Expert opinion: Efflux pumps are new targets for the development of adjuvant in antibiotic treatments by of efflux pump inhibition. They may allow us to rejuvenate old antibiotics acting on their concentration inside the bacteria and thus potentiating their activity while blocking the release of virulence factors. It is a pharmacodynamic challenge to finalize new combined therapy.
authors.affiliation: a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alibert
authors.affiliation: a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
authors.forename: Joannah
authors.initials: J
authors.lastname: N'gompaza Diarra
authors.affiliation: a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hernandez
authors.affiliation: a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Stutzmann
authors.affiliation: b Pharmaceutical Chemistry Department, Faculty of Pharmacy , Cairo University , Giza , Egypt.
authors.forename: Marwa
authors.initials: M
authors.lastname: Fouad
authors.affiliation: a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Boyer
authors.affiliation: a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins
keywords: Efflux pump; Gram-negative bacteria; antibiotic; inhibitor; multidrug resistance