{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:07:30Z","timestamp":1792804050975,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NWO XS","award":["OCENW.XS23.2.020"],"award-info":[{"award-number":["OCENW.XS23.2.020"]}]},{"name":"NWO Open Mind","award":["21559"],"award-info":[{"award-number":["21559"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>When bacteria are treated with multiple antibiotics simultaneously, resistance is highly unlikely to evolve. In contrast, resistance against multiple phages frequently arises during therapy. Why does resistance against multi-phage cocktails evolve so easily? Using a mathematical model, we show how the bacterial evolutionary dynamics and phage replicative dynamics uniquely intertwine, facilitating the rapid evolution of multi-phage resistance. As different phages replicate and become inhibitory at varying time points, bacteria can sequentially acquire resistance rather than simultaneously\u2014increasing the chance of multi-resistance by orders of magnitude. We predict and experimentally verify a regime where multi-phage resistance is robustly prevented. Our findings provide a framework for the rational design of phage cocktails to curtail resistance development. Resistance can be minimized by reducing the dose of the most potent phages or by using phages with longer latent periods, as this helps synchronize multi-phage selection.<\/jats:p>","DOI":"10.1093\/ismejo\/wrag067","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:44:16Z","timestamp":1774615456000},"source":"Crossref","is-referenced-by-count":3,"title":["Rapid resistance evolution against phage cocktails"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-4814","authenticated-orcid":false,"given":"Baltus A","family":"van der Steen","sequence":"first","affiliation":[{"name":"Molecular Microbiology Section, Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam , de Boelelaan 1108, 1081 BT Amsterdam, NH ,","place":["The Netherlands"]},{"name":"Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam , de Boelelaan 1108, 1081 BT Amsterdam, NH ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4599-1859","authenticated-orcid":false,"given":"Matti","family":"Gralka","sequence":"additional","affiliation":[{"name":"Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam , de Boelelaan 1108, 1081 BT Amsterdam, NH ,","place":["The Netherlands"]},{"name":"System Biology Section, Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam , de Boelelaan 1108, 1081 BT Amsterdam, NH ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-0977","authenticated-orcid":false,"given":"Yuval","family":"Mulla","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam , de Boelelaan 1108, 1081 BT Amsterdam, NH ,","place":["The Netherlands"]},{"name":"Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam , de Boelelaan 1108, 1081 BT Amsterdam, NH ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"2026052211370005300_ref1","doi-asserted-by":"publisher","first-page":"666","DOI":"10.3390\/nu11030666","article-title":"PHAGE study: effects of supplemental bacteriophage intake on inflammation and gut microbiota in healthy adults","volume":"11","author":"Febvre","year":"2019","journal-title":"Nutrients"},{"key":"2026052211370005300_ref2","doi-asserted-by":"publisher","first-page":"130","DOI":"10.4161\/bact.20757","article-title":"The strange history of phage therapy","volume":"2","author":"Summers","year":"2012","journal-title":"Bacteriophage"},{"key":"2026052211370005300_ref3","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"2026052211370005300_ref4","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/s41564-024-01705-x","article-title":"Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study","volume":"9","author":"Pirnay","year":"2024","journal-title":"Nat Microbiol"},{"key":"2026052211370005300_ref5","doi-asserted-by":"publisher","first-page":"e01258","DOI":"10.1128\/spectrum.01258-23","article-title":"Designing phage cocktails to combat the emergence of bacteriophage-resistant mutants in multidrug-resistant Klebsiella pneumoniae","volume":"12","author":"Yoo","year":"2023","journal-title":"Microbiol Spectrum"},{"key":"2026052211370005300_ref6","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/s41564-024-01913-5","article-title":"Engineered mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models","volume":"10","author":"Wang","year":"2025","journal-title":"Nat Microbiol"},{"key":"2026052211370005300_ref7","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1056\/NEJM199709113371101","article-title":"A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. 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