Efflux pumps

Efflux pumps are membrane transport proteins found in bacteria that actively pump antimicrobial agents out of the cell, reducing their intracellular concentration and contributing to antibiotic resistance. These pumps can extrude a wide range of antibiotics, making them a significant mechanism of multidrug resistance (MDR). There are several types of efflux pumps, classified based on their structure, energy source, and substrate specificity. Here are some common types:

1. ATP-Binding Cassette (ABC) Transporters:

   • ABC transporters are energy-dependent efflux pumps that utilize ATP hydrolysis to transport substrates across the membrane.
   • Examples include:
     • PmrA/PmrB: Confers resistance to polymyxins in Gram-negative bacteria.
     • LmrA: Found in Lactococcus lactis and confers resistance to multiple antibiotics.
     • MsrA/MsrB: Involved in macrolide resistance in Staphylococcus aureus.
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2. Resistance-Nodulation-Division (RND) Transporters:

   • RND transporters are tripartite efflux systems composed of an inner membrane pump, a periplasmic adaptor protein, and an outer membrane channel.
   • These pumps use the proton motive force to extrude substrates across the outer membrane.
   • Examples include:
     • AcrAB-TolC: Confers resistance to a wide range of antibiotics in Enterobacteriaceae.
     • MexAB-OprM: Found in Pseudomonas aeruginosa and mediates resistance to multiple antibiotics.
     • CmeABC: Involved in resistance to antibiotics in Campylobacter spp.
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3. Major Facilitator Superfamily (MFS) Transporters:

   • MFS transporters are secondary active transporters that use the electrochemical gradient to drive substrate transport.
   • They typically catalyze uniport, symport, or antiport of substrates across the membrane.
   • Examples include:
     • NorA: Found in Staphylococcus aureus and confers resistance to fluoroquinolones.
     • TetA: Confers resistance to tetracyclines in various bacterial species.
     • EmrAB: Involved in multidrug resistance in Escherichia coli.
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4. Small Multidrug Resistance (SMR) Family:

   • SMR transporters are small membrane proteins that typically function as homodimers and catalyze proton-driven antiport of substrates.
   • They are commonly found in Gram-positive bacteria and mitochondria.
   • Examples include:
     • QacA/B: Confers resistance to quaternary ammonium compounds and other cationic disinfectants.
     • EmrE: Mediates multidrug resistance in Escherichia coli.
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5. Multidrug and Toxic Compound Extrusion (MATE) Family:

   • MATE transporters are secondary active transporters that use the proton motive force to export substrates out of the cell.
   • They are widespread in bacteria and play a role in resistance to multiple antibiotics and toxic compounds.
   • Examples include:
     • NorM: Confers resistance to multiple antibiotics in various bacterial species.
     • MepA: Found in Staphylococcus aureus and contributes to multidrug resistance.

Efflux pumps are crucial determinants of bacterial resistance to antimicrobial agents and contribute to the persistence of infections caused by MDR pathogens. Understanding the diversity and mechanisms of efflux pumps is essential for the development of strategies to combat antibiotic resistance.