Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer

Science. 2019 May 24;364(6442):778-782. doi: 10.1126/science.aav6390.


Drug-resistance dissemination by horizontal gene transfer remains poorly understood at the cellular scale. Using live-cell microscopy, we reveal the dynamics of resistance acquisition by transfer of the Escherichia coli fertility factor-conjugation plasmid encoding the tetracycline-efflux pump TetA. The entry of the single-stranded DNA plasmid into the recipient cell is rapidly followed by complementary-strand synthesis, plasmid-gene expression, and production of TetA. In the presence of translation-inhibiting antibiotics, resistance acquisition depends on the AcrAB-TolC multidrug efflux pump, because it reduces tetracycline concentrations in the cell. Protein synthesis can thus persist and TetA expression can be initiated immediately after plasmid acquisition. AcrAB-TolC efflux activity can also preserve resistance acquisition by plasmid transfer in the presence of antibiotics with other modes of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antiporters / antagonists & inhibitors
  • Antiporters / biosynthesis
  • Antiporters / genetics
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Conjugation, Genetic
  • DNA, Single-Stranded
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / physiology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / physiology*
  • F Factor / genetics
  • F Factor / physiology*
  • Microscopy
  • Protein Biosynthesis / drug effects
  • Tetracycline / pharmacology


  • AcrAB-TolC protein, E coli
  • Anti-Bacterial Agents
  • Antiporters
  • Bacterial Proteins
  • Carrier Proteins
  • DNA, Single-Stranded
  • Escherichia coli Proteins
  • tetA protein, Bacteria
  • Tetracycline