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Here we show that the evolution of multi-drug-resistant <jats:italic>Escherichia coli<\/jats:italic> can be manipulated <jats:italic>in vitro<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/ncomms15589","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T11:12:46Z","timestamp":1496920366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro"],"prefix":"10.1038","volume":"8","author":[{"given":"Mari","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Gali\u00f1anes","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Tsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Horinouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikara","family":"Furusawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-5757","authenticated-orcid":false,"given":"Leroy","family":"Cronin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,8]]},"reference":[{"key":"BFncomms15589_CR1","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S1473-3099(13)70318-9","volume":"13","author":"R Laxminarayan","year":"2013","unstructured":"Laxminarayan, R. et al. 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