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

Yoshida, M. , Galiñanes Reyes, S. G., Tsuda, S., Horinouchi, T., Furusawa, C. and Cronin, L. (2017) Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro. Nature Communications, 8, 15589. (doi: 10.1038/ncomms15589) (PMID:28593940) (PMCID:PMC5472167)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yoshida, Mari and Galinanes Reyes, Miss Sabrina and Tsuda, Dr Soichiro and Cronin, Professor Lee
Authors: Yoshida, M., Galiñanes Reyes, S. G., Tsuda, S., Horinouchi, T., Furusawa, C., and Cronin, L.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Nature Communications 8:15589
Publisher Policy:Reproduced under a Creative Commons License

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