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Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro

Author

Listed:
  • Mari Yoshida

    (WestCHEM, School of Chemistry, The University of Glasgow)

  • Sabrina Galiñanes Reyes

    (WestCHEM, School of Chemistry, The University of Glasgow)

  • Soichiro Tsuda

    (WestCHEM, School of Chemistry, The University of Glasgow)

  • Takaaki Horinouchi

    (Quantitative Biology Center, RIKEN)

  • Chikara Furusawa

    (Quantitative Biology Center, RIKEN
    University of Tokyo)

  • Leroy Cronin

    (WestCHEM, School of Chemistry, The University of Glasgow)

Abstract

Multi-drug strategies have been attempted to prolong the efficacy of existing antibiotics, but with limited success. Here we show that the evolution of multi-drug-resistant Escherichia coli can be manipulated in vitro by administering pairs of antibiotics and switching between them in ON/OFF manner. Using a multiplexed cell culture system, we find that switching between certain combinations of antibiotics completely suppresses the development of resistance to one of the antibiotics. Using this data, we develop a simple deterministic model, which allows us to predict the fate of multi-drug evolution in this system. Furthermore, we are able to reverse established drug resistance based on the model prediction by modulating antibiotic selection stresses. Our results support the idea that the development of antibiotic resistance may be potentially controlled via continuous switching of drugs.

Suggested Citation

  • Mari Yoshida & Sabrina Galiñanes Reyes & Soichiro Tsuda & Takaaki Horinouchi & Chikara Furusawa & Leroy Cronin, 2017. "Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15589
    DOI: 10.1038/ncomms15589
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    Cited by:

    1. Teemu Kuosmanen & Johannes Cairns & Robert Noble & Niko Beerenwinkel & Tommi Mononen & Ville Mustonen, 2021. "Drug-induced resistance evolution necessitates less aggressive treatment," PLOS Computational Biology, Public Library of Science, vol. 17(9), pages 1-22, September.

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