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

  title={Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria},
  author={Julia Vergalli and Igor V. Bodrenko and Muriel Masi and Lucile Moyni{\'e} and Silvia Acosta-Guti{\'e}rrez and J. Naismith and Anne Davin-Regli and Matteo Ceccarelli and Bert van den Berg and Mathias Winterhalter and Jean-Marie Pag{\'e}s},
  journal={Nature Reviews Microbiology},
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… 
Outer membrane permeability: Antimicrobials and diverse nutrients bypass porins in Pseudomonas aeruginosa
Porin-independent permeation of antibiotics through the outer-membrane lipid bilayer was hampered by carboxylate groups, consistent with nutrient data, and challenge common assumptions about the role of porins.
Measurement of Accumulation of Small Molecules into Gram-negative Bacteria
The development of the Bacterial Chloro-Alkane Penetration Assay (BaCAPA), which employs the use of a genetically encoded protein called HaloTag, to measure the uptake and accumulation of molecules into Gram-negative bacteria, is described.
Role of the lipid bilayer in outer membrane protein folding in Gram-negative bacteria
The roles of the lipid environment and the OM in modulating the OMP-folding landscape are highlighted and an understanding of the folding properties of OMPs in vitro can help explain the challenges they encounter during folding in vivo is explained.
Assembly and Maintenance of Lipids at the Bacterial Outer Membrane.
This Review describes the trans-envelope lipid transport systems that have been identified to participate in outer-membrane biogenesis: LPS transport through the Lpt machine, and phospholipid transport via the Mla pathway and several recently proposed transporters.
The Whole Is Bigger than the Sum of Its Parts: Drug Transport in the Context of Two Membranes with Active Efflux.
This review surveys key experimental and computational approaches to the investigation of transport by individual translocators and in whole cells, summarizes key findings from these studies and outlines implications for antibiotic discovery.
Antibiotic uptake through porins located in the outer membrane of Gram-negative bacteria
  • M. Winterhalter
  • Biology, Environmental Science
    Expert opinion on drug delivery
  • 2020
A larger dataset of single channel permeabilities under various condition will be a powerful tool for understanding and improving the activity of antibiotics.
Kanamycin uptake into Escherichia coli is facilitated by OmpF and OmpC porin channels located in the outer membrane.
Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here,
The crystal structure of the TonB-dependent transporter YncD reveals a positively charged substrate binding site
The structure and phylogenetic distribution of the TonB-dependent transporter YncD are determined, showing that despite a distant evolutionary relationship, it shares structural features with the ferriccitrate transporter FecA, including a compact positively-charged substrate-binding site.


The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria
The bacterial response towards antibiotic stress on altered membrane permeability is outlined and recent advances in molecular approaches that are improving knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channels are discussed.
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
  • H. Nikaido
  • Biology
    Microbiology and Molecular Biology Reviews
  • 2003
This review summarizes the development in the field since the previous review and begins to understand how this bilayer of the outer membrane can retard the entry of lipophilic compounds, owing to increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopoly Saccharide structure is modified by environmental conditions.
Outer Membrane Porins.
This work highlights some recent structural biology reports and functional assays that have substantially contributed to understanding of the mechanism that mediates uptake of small molecules, including antibiotics, across the outer membrane of Enterobacteriaceae and reviews advances in the regulation of porin expression and porin biogenesis.
Membrane permeability and regulation of drug "influx and efflux" in enterobacterial pathogens.
In Enterobacteriaceae, membrane permeability is a key in the level of susceptibility to antibiotics. Modification of the bacterial envelope by decreasing the porin production or increasing the
Mechanisms of envelope permeability and antibiotic influx and efflux in Gram-negative bacteria
The biological underpinnings of drug permeability and export using several prototypical influx and efflux systems are discussed, highlighting how new methods for the determination of antibacterial activities enable more careful quantitation and may provide a way forward for capturing and correlating the modes of action and kinetics of antibiotic uptake inside bacterial cells.
Gram-negative trimeric porins have specific LPS binding sites that are essential for porin biogenesis
Specific LPS binding sites are revealed on OM porin proteins that allow them to stabilize, rather than disrupt, the ordered network of LPS molecules, and it is demonstrated that one such site is essential for porin assembly in the OM.
Ampicillin permeation across OmpF, the major outer-membrane channel in Escherichia coli
It is found that the solute-induced ion current fluctuation is 10 times higher with penicilloic acid than with ampicillin, and OmpF can impose selective permeation on similar sized molecules based on their structure and their dipolar properties.
Microbe-Host Interactions: Structure and Role of Gram-Negative Bacterial Porins
The role that porins play in activating immunological responses, in inducing signaling pathways and their influence on antibiotic resistance mechanisms that involve modifications of the properties of the OM lipid barrier are discussed.
Bacterial Outer Membrane Porins as Electrostatic Nanosieves: Exploring Transport Rules of Small Polar Molecules.
A general model for transport of polar molecules through these electrostatic nanosieves is proposed, helping to further understand the basis for permeability in Gram-negative pathogens, contributing to fill in the innovation gap that has limited the discovery of effective antibiotics in the last 20 years.
Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores
It is hypothesized that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have “evolved” to be channel-specific.