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From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins
09:55

From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins

Published on: July 4, 2016

Structure, Function and Regulation of Outer Membrane Proteins Involved in Drug Transport in Enterobactericeae: the

Muriel Masi1, Jean-Marie Pagès

  • 1CNRS-UMR 8619, Institut de Biophysique et de Biochimie Moléculaire et Cellulaire (IBBMC), Université Paris Sud, Orsay, France.

The Open Microbiology Journal
|April 10, 2013
PubMed

Insights

Gram-negative bacteria resist antibiotics by controlling membrane permeability through porins and TolC-like efflux pumps. Understanding these transport mechanisms is crucial for combating multidrug resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Gram-negative bacteria possess outer membranes that act as a barrier against antibiotics.
  • Resistance mechanisms often involve altering membrane permeability to limit antibiotic entry or facilitate efflux.
  • Multidrug resistance (MDR) is a significant clinical challenge, often linked to changes in bacterial membranes.

Purpose of the Study:

  • To review the structure, function, and regulation of porins and TolC-like channels in Enterobacteriaceae.
  • To elucidate the role of these membrane proteins in antibiotic transport and bacterial resistance.
  • To provide an updated understanding of antibiotic translocation mechanisms in the context of MDR.

Main Methods:

  • Literature review of recent studies on porins and TolC-like proteins.
  • Analysis of structural and functional data related to antibiotic transport.
  • Synthesis of information on porin assembly, regulation, and contribution to resistance.

Main Results:

  • General porins (e.g., OmpF/C) control the entry of hydrophilic antibiotics like beta-lactams and fluoroquinolones.
  • TolC-like proteins, part of multidrug efflux pumps, mediate the exit of a broad range of antibiotics.
  • Altered membrane permeability via porin modification or efflux pump overexpression is a hallmark of MDR in clinical isolates.

Conclusions:

  • Porins and TolC-like efflux pumps are critical determinants of antibiotic susceptibility and resistance in Gram-negative bacteria.
  • Understanding the intricate mechanisms of antibiotic transport through these channels is essential for developing new therapeutic strategies.
  • Continuous updates on antibiotic transport knowledge are vital to counteract evolving MDR strains.
Keywords:
AntibioticsEfflux pumpsMembrane permeabilityMultidrug resistancePorins.

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