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Strategy 2: Eliminating antimicrobial agents from the cell with expulsion via efflux pumps.

To be effective, antimicrobial agents must also be present at a sufficiently high concentration within the bacterial cell.  Some bacteria possess membrane proteins that act as an export or efflux pump for certain antimicrobials, extruding the antibiotic out of the cell as fast as it can enter.  This results in low intracellular concentrations that are insufficient to elicit an effect.  Some efflux pumps selectively extrude specific antibiotics such as macrolides, lincosamides, streptogramins and tetracyclines, whereas others (referred to as multiple drug resistance pumps) expel a variety of structurally diverse anti-infectives with different modes of action. 

This strategy has been observed in:

  • E.coli and other Enterobacteriaceae against tetracyclines
  • Enterobacteriaceae against chloramphenicol
  • Staphylococci against macrolides and streptogramins
  • Staphylococcus aureus and Streptococcus pneumoniae against fluoroquinolones

 

Trivia: Efflux pumps

These efflux pumps are variants of membrane pumps possessed by all bacteria, both pathogenic and non-pathogenic, to move lipophilic or amphipathic molecules in and out of the cells.  Some are used by antibiotic producers to pump antibiotics out of the cells as fast as they are made, and so constitute an immunity protective mechanism for the bacteria to prevent being killed by their own chemical weapons (Walsh, 2000).

 

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