title: Efflux Pump Blockers in Gram-Negative Bacteria: The New Generation of Hydantoin Based-Modulators to Improve Antibiotic Activity.
abstract: Multidrug resistant (MDR) bacteria are an increasing health problem with the shortage of new active antibiotic agents. Among effective mechanisms that contribute to the spread of MDR Gram-negative bacteria are drug efflux pumps that expel clinically important antibiotic classes out of the cell. Drug pumps are attractive targets to restore the susceptibility toward the expelled antibiotics by impairing their efflux activity. Arylhydantoin derivatives were investigated for their potentiation of activities of selected antibiotics described as efflux substrates in Enterobacter aerogenes expressing or not AcrAB pump. Several compounds increased the bacterial susceptibility toward nalidixic acid, chloramphenicol and sparfloxacin and were further pharmacomodulated to obtain a better activity against the AcrAB producing bacteria.
authors.affiliation: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian UniversityKrakow, Poland; UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de PharmacieMarseille, France.
authors.forename: Ewa
authors.initials: E
authors.lastname: Otręebska-Machaj
authors.affiliation: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.affiliation: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.affiliation: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szymańska
authors.affiliation: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Schabikowski
authors.affiliation: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Boyer
authors.affiliation: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bolla
authors.affiliation: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
authors.affiliation: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
authors.affiliation: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alibert
keywords: AcrAB pump; antibiotics; efflux pump blocker; hydantoin; multidrug resistance