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

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 inEnterobacteriaceae. 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.