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Related Experiment Videos

Antibiotic efflux pumps.

F Van Bambeke1, E Balzi, P M Tulkens

  • 1Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Brussels, Belgium. vanbambeke@facm.ucl.ac.be

Biochemical Pharmacology
|June 30, 2000
PubMed
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Antibiotic efflux pumps in cells significantly impact drug activity and resistance. Understanding these pumps is crucial for developing new antimicrobial therapies and combating infectious diseases effectively.

Area of Science:

  • Microbiology
  • Pharmacology
  • Molecular Biology

Background:

  • Active efflux by antibiotic pumps modulates drug activity in both prokaryotic and eukaryotic cells.
  • Numerous drug efflux pump classes facilitate effective antibiotic transport.
  • These pumps are implicated in both intrinsic and acquired antimicrobial resistance.

Purpose of the Study:

  • To review the classification and significance of antibiotic efflux pumps in prokaryotic and eukaryotic cells.
  • To highlight the role of efflux pumps in antimicrobial resistance and their impact on therapeutic outcomes.
  • To emphasize the importance of considering efflux pumps in the development of novel antimicrobials.

Main Methods:

  • Classification of primary active transporters (ATP-binding cassette superfamily) and secondary active transporters (SMR, MET, MAR, RND, MFS superfamilies) involved in antibiotic efflux.

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  • Review of literature on the substrate specificity, expression, and mechanisms of antibiotic efflux pumps.
  • Analysis of the role of efflux pumps in modulating antimicrobial accumulation and transport in host cells.

    • Main Results:

    • Six families of ATP-binding cassette superfamily pumps (e.g., P-glycoprotein, MRP) and ten families across five superfamilies of secondary active transporters (SMR, MET, MAR, RND, MFS) are responsible for antibiotic efflux.
    • Antibiotic efflux pumps contribute significantly to acquired bacterial resistance due to broad substrate recognition and cooperation with other resistance mechanisms.
    • In eukaryotes, these pumps regulate antimicrobial levels in phagocytic cells and are key in transepithelial transport.

    Conclusions:

    • Antibiotic efflux pumps are critical determinants of antimicrobial efficacy and resistance.
    • Their involvement in intrinsic and acquired resistance necessitates their consideration in antimicrobial drug design.
    • Targeting antibiotic efflux pumps with specific inhibitors presents a promising strategy for future infectious disease control.