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Frontiers in microbiology
2016;7 622.

Efflux Pump Blockers in Gram-Negative Bacteria: The New Generation of Hydantoin Based-Modulators to Improve Antibiotic Activity.

Ewa Otręebska-Machaj, Jacqueline Chevalier, Jadwiga Handzlik, Ewa Szymańska, Jakub Schabikowski, Gérard Boyer, Jean-Michel Bolla, Katarzyna Kieć-Kononowicz, Jean-Marie Pagès, Sandrine Alibert
Author Information
  1. Ewa Otręebska-Machaj: 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.
  2. Jacqueline Chevalier: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
  3. Jadwiga Handzlik: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
  4. Ewa Szymańska: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
  5. Jakub Schabikowski: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
  6. Gérard Boyer: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
  7. Jean-Michel Bolla: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
  8. Katarzyna Kieć-Kononowicz: Department of Technology and Biotechnology of Drugs, Medical College, Jagiellonian University Krakow, Poland.
  9. Jean-Marie Pagès: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
  10. Sandrine Alibert: UMR-MD1, Aix Marseille Université/IRBA, Facultés de Médecine et de Pharmacie Marseille, France.
PMID: 27199950 DOI: 10.3389/fmicb.2016.00622

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.

Keywords

AcrAB pump antibiotics efflux pump blocker hydantoin multidrug resistance

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