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Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria

Nature Reviews Microbiology volume 18, pages 164–176 (2020)Cite this article

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Abstract

Gram-negative bacteria and their complex cell envelope, which comprises an outer membrane and an inner membrane, are an important and attractive system for studying the translocation of small molecules across biological membranes. In the outer membrane of Enterobacteriaceae, trimeric porins control the cellular uptake of small molecules, including nutrients and antibacterial agents. The relatively slow porin-mediated passive uptake across the outer membrane and active efflux via efflux pumps in the inner membrane creates a permeability barrier. The synergistic action of outer membrane permeability, efflux pump activities and enzymatic degradation efficiently reduces the intracellular concentrations of small molecules and contributes to the emergence of antibiotic resistance. In this Review, we discuss recent advances in our understanding of the molecular and functional roles of general porins in small-molecule translocation in Enterobacteriaceae and consider the crucial contribution of porins in antibiotic resistance.

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Fig. 1: Structural aspects of enterobacterial porins.
Fig. 2: Structural differences in enterobacterial porins have implications for permeation and antibiotic resistance.
Fig. 3: Mechanism of translocation and model of permeation of molecules through general porins.

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Acknowledgements

The authors gratefully acknowledge R. A. Stavenger for stimulating and helpful discussions. The research leading to this article was conducted as part of the TRANSLOCATION consortium, and it has received support from the Innovative Medicines Initiatives Joint Undertaking under Grant Agreement no. 115525, resources that are composed of financial contributions from the European Union’s seventh framework programme (FP7/2007–2013) and the European Federation of Pharmaceutical Industries and Associations companies in kind contribution. J.M.P. was also partially supported by Aix-Marseille Université, Service de Santé des Armées and INSERM. M.C. was partially supported by the Italian MIUR, PRIN Project 2015795S5W_005. L.M. was also supported by the ND4BB ENABLE Consortium under grant agreement no. 115583. The authors apologize to those researchers whose articles are not cited owing to space limitations.

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Nature Reviews Microbiology thanks H. Zgurskaya, S. Bezrukov and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Author notes

  1. These authors contributed equally: Julia Vergalli, Igor V. Bodrenko, Muriel Masi

Authors and Affiliations

  1. UMR-MD1, U-1261, Aix-Marseille Université, INSERM, SSA, IRBA, MCT, Faculté de Pharmacie, Marseille, France

    Julia Vergalli, Muriel Masi, Anne Davin-Regli & Jean-Marie Pagès

  2. Department of Physics, University of Cagliari, Cagliari, Italy

    Igor V. Bodrenko, Silvia Acosta-Gutiérrez & Matteo Ceccarelli

  3. CNR/IOM, Cittadella Universitaria di Monserrato, Monserrato, Italy

    Igor V. Bodrenko, Silvia Acosta-Gutiérrez & Matteo Ceccarelli

  4. Institut de Biologie Intégrative de la Cellule (I2BC), UMR9198, CNRS, CEA, Université Paris Sud, Université Paris Saclay, Gif-sur-Yvette, France

    Muriel Masi

  5. Division of Structural Biology, Nuffield Department of Medicine, Oxford, UK

    Lucile Moynié & James H. Naismith

  6. Rosalind Franklin Institute, Rutherford Appleton Laboratory, Didcot, UK

    Lucile Moynié & James H. Naismith

  7. Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, UK

    Bert van den Berg

  8. Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany

    Mathias Winterhalter

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Contributions

All authors researched data for article. J.-M.P., J.V., I.V.B., M.M., L.M., J.H.N., A.D.-R., M.C., B.v.d.B. and M.W. contributed substantially to the discussion of the content. J.-M.P., J.V., I.V.B., M.M., L.M., S.A.-G., J.H.N., M.C., B.v.d.B. and M.W. wrote the article. and J.-M.P., J.V., J.H.N., M.C., B.v.d.B. and M.W. reviewed and edited the manuscript before submission.

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Correspondence to Jean-Marie Pagès.

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TRANSLOCATION consortium: https://www.imi.europa.eu/projects-results/project-factsheets/translocation

Supplementary information

Glossary

β-barrels

β-barrels comprise an even number of β-strands, ranging from 8 to 24, that are arranged in an antiparallel fashion.

β-Lactamases

Bacterial enzymes located in the periplasm of Gram-negative bacteria that cleave β-lactam antibiotics such as penicillins, cephalosporins and carbapenems.

Counterion

Ion accompanying a charged amino acid to maintain charge neutrality. Whereas the amino acid is fixed, the counterion is solubilized in the aqueous phase and moves with the electric field.

Graphics processing units

Hardware components of a computer able to increase computational speed by performing parallel calculations. They are typically used for gaming, but their use has been extended to use by scientific software that runs much faster (a factor of 10–100) than on a normal central processing unit.

Dipole moment

Electric dipole moment applied to compounds or molecules. It provides information on the distribution of charges in the scaffold. A zwitterionic molecule possesses a large dipole when the two charged groups are far apart.

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Vergalli, J., Bodrenko, I.V., Masi, M. et al. Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria. Nat Rev Microbiol 18, 164–176 (2020). https://doi.org/10.1038/s41579-019-0294-2

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