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 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.

Molecular Characterization of Carbapenemase-Nonproducing Clinical Isolates of <i>Escherichia coli</i> (from a Thai University Hospital) with Reduced Carbapenem Susceptibility

“…Carbapenem resistance can develop via porin loss or mutations in genes encoding porins, particularly in their constriction L3 loop region (24,25). In the present study, the frequency of an OmpF defect manifesting itself as a truncated protein (7 out of 11 isolates) is higher than that of OmpC defects (no truncated proteins in any isolate), in agreement with the in vitro study by Adler et al (26).…”

Conventional Antibiotics – Revitalized by New Agents

“…In the case of fluoroquinolones, outer membrane proteins play a key part in helping these molecules to cross the membrane [49,50]. In contrast, passive diffusion is thought to be important for translocation of the inner membrane of Gram-negatives and the single membrane of Gram-positives [51,52,53,54].…”

Stress responses, outer membrane permeability control and antimicrobial resistance in Enterobacteriaceae

“…Given the importance of the OM in controlling the uptake of beneficial as well as toxic compounds, one can expect that the expression of porins depends on environmental stresses and is well coordinated at the transcriptional and post-transcriptional levels [10,[14][15][16][17]. In this review, we will address the porin-mediated influx of antibiotics and give a perspective on the factors, including major regulatory pathways and antibiotic stresses, which control porin expression in E. coli and closely relative Enterobacteriaceae.…”