Structure, Function and Regulation of Outer Membrane Proteins Involved in Drug Transport in Enterobactericeae: the OmpF/C – TolC Case



Muriel Masi 1, Jean-Marie Pagès 2, 3, *
1 CNRS-UMR 8619, Institut de Biophysique et de Biochimie Moléculaire et Cellulaire (IBBMC), Université Paris Sud, Orsay, France
2 UMR-MD1, Université d’Aix-Marseille, IRBA, Marseille, France
3 COST Action BM0701 (ATENS), Brusells, Belgium


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© Masi and Pages; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the UMR-MD1, Transporteurs Membranaires, Chimiorésistance et Drug Design, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France; Tel: (33) 4 91 32 45 87; Fax: (33) 4 91 32 46 06; E-mail: jean-marie.pages@univmed.fr


Abstract

Antibiotic translocation across membranes of Gram-negative bacteria is a key step for the activity on their specific intracellular targets. Resistant bacteria control their membrane permeability as a first line of defense to protect themselves against external toxic compounds such as antibiotics and biocides. On one hand, resistance to small hydrophilic antibiotics such as ß-lactams and fluoroquinolones frequently results from the « closing » of their way in: the general outer membrane porins. On the other hand, an effective way out for a wide range of antibiotics is provided by TolC-like proteins, which are outer membrane components of multidrug efflux pumps. Accordingly, altered membrane permeability, including porin modifications and/or efflux pumps’ overexpression, is always associated to multidrug resistance (MDR) in a number of clinical isolates.

Several recent studies have highlighted our current understanding of porins/TolC structures and functions in Enterobacteriaceae. Here, we review the transport of antibiotics through the OmpF/C general porins and the TolC-like channels with regards to recent data on their structure, function, assembly, regulation and contribution to bacterial resistance.

Because MDR strains have evolved global strategies to identify and fight our antibiotic arsenal, it is important to constantly update our global knowledge on antibiotic transport.

Keywords: Antibiotics, Efflux pumps, Membrane permeability, Multidrug resistance, Porins.