title: Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria.
abstract: In Gram-negative bacteria, the envelope is a sophisticated barrier protecting the cell against external toxic compounds. Membrane transporters, e.g., porins or efflux pumps, are main filters regulating the internal accumulation of various hydrophilic molecules. Regarding bacterial susceptibility towards antibacterial agents, membrane permeability is part of the early bacterial defense. The bacterium manages the translocation process, influx and efflux, to control the intracellular concentration of various molecules. Antibiotics and biocides are substrates of these mechanisms and the continuing emergence of multidrug resistant isolates is a growing worldwide health concern. Different strategies could be proposed to bypass the bacterial membrane barrier, comprising influx and efflux mechanisms, in order to restore the activity of antibiotics against resistant bacteria.
authors.affiliation: UMR-MD1, Transporteurs Membranaires, Chimiorésistance et Drug Design, Facultés de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bolla
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alibert-Franco
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Abdallah
authors.initials: A
authors.lastname: Mahamoud
authors.forename: Gérard
authors.initials: G
authors.lastname: Boyer
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D006090:Gram-Negative Bacteria / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents