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Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only \u03b2-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.\n                  <\/jats:p>","DOI":"10.7554\/elife.68876","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T08:00:29Z","timestamp":1627459229000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68876","source":"Crossref","is-referenced-by-count":61,"title":["High potency of sequential therapy with only \u03b2-lactam antibiotics"],"prefix":"10.7554","volume":"10","author":[{"given":"Aditi","family":"Batra","sequence":"first","affiliation":[{"name":"Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany"},{"name":"Max Planck Institute for Evolutionary Biology, Ploen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-5261","authenticated-orcid":true,"given":"Roderich","family":"Roemhild","sequence":"additional","affiliation":[{"name":"Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany"},{"name":"Max Planck Institute for Evolutionary Biology, Ploen, Germany"},{"name":"Institute of Science and Technology, Klosterneuburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Borstel Research Centre, National Reference Center for Mycobacteria, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6ren","family":"Franzenburg","sequence":"additional","affiliation":[{"name":"Competence Centre for Genomic Analysis Kiel, University of Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-0684","authenticated-orcid":true,"given":"Stefan","family":"Niemann","sequence":"additional","affiliation":[{"name":"Borstel Research Centre, National Reference Center for Mycobacteria, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-913X","authenticated-orcid":true,"given":"Hinrich","family":"Schulenburg","sequence":"additional","affiliation":[{"name":"Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany"},{"name":"Max Planck Institute for Evolutionary Biology, Ploen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1111\/evo.12034","article-title":"Stochastic temperatures impede rna virus adaptation","volume":"67","author":"Alto","year":"2013","journal-title":"Evolution"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1093\/femsre\/fuaa001","article-title":"Antibiotic resistance: turning evolutionary principles into clinical reality","volume":"44","author":"Andersson","year":"2020","journal-title":"FEMS Microbiology Reviews"},{"key":"bib3","article-title":"FastQC: A Quality Control Tool for High Throughput Sequence Data","volume-title":"Babraham Bioinformatics","author":"Andrews","year":"2010","unstructured":"Andrews S. 2010. 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