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

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Science  24 May 2019:
Vol. 364, Issue 6442, pp. 778-782
DOI: 10.1126/science.aav6390

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A race against time

Clinically relevant antimicrobial resistance is largely spread via plasmids that disperse among bacteria during conjugation. How quickly can a resistance gene be expressed after transfer? In susceptible bacterial cells, tetracycline should inhibit protein synthesis, including from the plasmid-transferred resistance gene tetA. Unexpectedly, Nolivos et al. found that TetA can be expressed despite the presence of tetracycline (see the Perspective by Povolo and Ackermann). Immediately after plasmid transfer into a cell, TetA synthesis starts because its repressor is slow to be expressed. In addition, the ubiquitous xenobiotic efflux pump AcrAB-TolC buys time for TetA translation by keeping tetracycline concentration below toxic levels.

Science, this issue p. 778; see also p. 737


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.

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