Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy
| Autor: | Jean-Marie Pagès, Winfried V. Kern, Jacqueline Chevalier, Abdallah Mahamoud, Sandrine Alibert-Franco |
|---|---|
| Přispěvatelé: | Transporteurs membranaires, chimioresistance et drug-design (TMCD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Infectious Diseases and Travel Medicine, University Hospital Freiburg, Alibert, Sandrine |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Microbiology (medical)
drug efflux pumps ATP Binding Cassette Transporter Subfamily B Gram-negative bacteria antibiotic resistance medicine.drug_class [CHIM.THER] Chemical Sciences/Medicinal Chemistry Antibiotics Biological Transport Active ATP-binding cassette transporter [CHIM.THER]Chemical Sciences/Medicinal Chemistry Microbiology 03 medical and health sciences Antibiotic resistance Gram-Negative Bacteria medicine Pharmacology (medical) 030304 developmental biology Antibacterial agent efflux pump inhibitors Pharmacology 0303 health sciences biology 030306 microbiology Membrane transport biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Anti-Bacterial Agents 3. Good health Infectious Diseases Biochemistry [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Quinolines [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Efflux [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Bacteria |
| Zdroj: | Journal of Antimicrobial Chemotherapy Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2007, 59 (6), pp.1223-1229. ⟨10.1093/jac/dkl493⟩ |
| ISSN: | 0305-7453 1460-2091 |
| DOI: | 10.1093/jac/dkl493⟩ |
| Popis: | International audience; After several decades of continuously successful antibiotic therapy against bacterial infections, we are now facing a worrying prospect: the accelerated evolution of antibiotic resistance to important human pathogens and the scarcity of new anti-infective drug families under development. Efflux is a general mechanism responsible for bacterial resistance to antibiotics. This active drug transport is involved in low intrinsic susceptibility, cross-resistance to chemically unrelated classes of molecules, and selec-tion/acquisition of additional mechanisms of resistance. Thus, inhibition of bacterial efflux mechanisms appears to be a promising target in order to (i) increase the intracellular concentration of antibiotics that are expelled by efflux pumps, (ii) restore the drug susceptibility of resistant clinical strains, and (iii) reduce the capability for acquired additional resistance. Structurally unrelated classes of efflux pump inhibitors (EPIs) have been described and tested in the last decade, including some analogues of antibiotic substrates and new chemical molecules. Among the current collection of EPIs, only a few compounds have been studied taking into account the structure– activity relationships and the spectrum of activity in terms of antibiotics, pumps and bacteria. While large efforts have characterized an increasing number of bacterial efflux pumps and generated several potentially active EPIs, they have not elucidated the molecular basis of efflux transport and inhibition. Recent studies of pump – substrate complexes, the 3D resolution of the efflux pumps, the synthesis of novel compounds and molecular dynamic studies may generate new clues to decipher and select novel targets inside the efflux mechanisms and, finally, may result in a clinically useful molecule. |
| Databáze: | OpenAIRE |
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