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Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):E2629-34. doi: 10.1073/pnas.1310333110. Epub 2013 Jun 24.

Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels.

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  • 1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.

Abstract

Small, hydrophilic compounds such as β-lactams diffuse across the outer membrane of Gram-negative bacteria through porin channels, which were originally thought to be nonspecific channels devoid of any specificity. However, since the discovery of an ampicillin-binding site within the OmpF channel in 2002, much attention has been focused on the potential specificity of the channel, where the binding site was assumed either to facilitate or to retard the penetration of β-lactams. Since the earlier studies on porin permeability were done without the knowledge of the contribution of multidrug efflux pumps in the overall flux process across the cell envelope, in this study we have carefully studied both the porin permeability and active efflux of ampicillin and benzylpenicillin. We found that the influx occurs apparently by a spontaneous passive diffusion without any indication of specific binding within the concentration range relevant to the antibiotic action of these drugs, and that the higher permeability for ampicillin is totally as expected from the gross property of this drug as a zwitterionic compound. The active efflux by AcrAB was more effective for benzylpenicillin due to the stronger affinity and high degree of positive cooperativity. Our data now give a complete quantitative picture of the influx, efflux, and periplasmic degradation (catalyzed by AmpC β-lactamase) of these two compounds, and correlate closely with the susceptibility of Escherichia coli strains used here, thus validating not only our model but also the parameters obtained in this study.

KEYWORDS:

AcrB; OmpC

PMID:
23798411
[PubMed - indexed for MEDLINE]
PMCID:
PMC3710850
Free PMC Article
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