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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
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Related Experiment Video

Updated: Oct 2, 2025

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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Molecular Determinants for OMF Selectivity in Tripartite RND Multidrug Efflux Systems.

Esther Boyer1, Jean Dessolin1, Margaux Lustig2

  • 1CBMN UMR 5248, Bordeaux INP, CNRS, Université de Bordeaux, 33600 Pessac, France.

Antibiotics (Basel, Switzerland)
|February 25, 2022
PubMed
Summary

A specific mutation in MexA enhances antibiotic resistance by promoting the assembly of tripartite efflux pumps. This finding reveals key molecular determinants for outer membrane factor recruitment in Gram-negative bacteria.

Keywords:
RNDantibiotic resistanceefflux pump

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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
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Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • Gram-negative bacteria utilize tripartite multidrug RND efflux systems for drug expulsion.
  • Previous structural studies showed limited contact between outer membrane factors (OMFs) and periplasmic adaptor proteins (PAPs), obscuring OMF recruitment mechanisms.

Purpose of the Study:

  • To investigate the role of a MexA Q93R mutation in tripartite efflux complex assembly and function.
  • To elucidate the molecular determinants governing OMF recruitment and selectivity.

Main Methods:

  • Expression of MexA-MexB-OprM and mutant strains.
  • Single-particle electron microscopy for structural analysis.
  • Biochemical assays to assess complex formation and function.

Main Results:

  • The MexA Q93R mutation increased antibiotic resistance and promoted tripartite complex formation with cognate and non-cognate OMFs.
  • MexAQ93R self-assembled into hexamers, suggesting altered interprotomer interactions.
  • OprM C-terminal deletion impaired complex formation with wild-type MexA but not with MexAQ93R.

Conclusions:

  • The Q93R MexA mutation and the OprM C-terminal peptide are critical for modulating tripartite efflux pump assembly.
  • These findings provide insights into the mechanisms of OMF selectivity during complex formation, even with components outside the direct interface.