{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:36:50Z","timestamp":1792528610795,"version":"4.5.0"},"reference-count":50,"publisher":"The Royal Society","issue":"1934","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000770","name":"University of Manchester","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000770","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2025,9,4]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    chronic lung infections pose serious challenges for phage therapy due to high between-patient strain diversity and rapid within-patient phenotypic and genetic diversification, necessitating simple predictors of efficacy to streamline phage cocktail design. We quantified bacteria\u2013phage infection networks (BPINs) for six phages against 900\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    clones previously isolated from 10 bronchiectasis infections (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 90 isolates per patient). BPIN structure varied extensively between patients. The efficacy of the six-phage cocktail against these diverse\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    populations was influenced by several factors. Cocktail efficacy increased with decreasing number and strength of individual resistances, as well as with increasing co-resistance modularity and phage dose. These results highlight simple BPIN metrics that could help guide the design of effective phage therapeutics. Resistance against some but not all the phages increased with higher number defence systems per genome, resulting in lower efficacy of the six-phage cocktail, suggesting that\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    strains with fewer defence systems are better candidates for phage therapy. Overall, our findings suggest that \u2018off the peg\u2019 phage therapeutics are unlikely to be broadly effective against\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    chronic respiratory infections, but that the design of personalised phage cocktails could be guided using simple BPIN metrics, and that defence systems per genome provide a useful rule of thumb for identifying highly treatable infections.\n                  <\/jats:p>\n                  <jats:p>This article is part of the discussion meeting issue \u2018The ecology and evolution of bacterial immune systems\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2024.0080","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T07:05:38Z","timestamp":1756969538000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Bacteria\u2013phage infection network structure and genomic defence system content predict efficacy of a phage therapy cocktail against\n                    <i>Pseudomonas aeruginosa<\/i>\n                    from chronic lung infections"],"prefix":"10.1098","volume":"380","author":[{"given":"Maisie R.","family":"Czernuszka","sequence":"first","affiliation":[{"name":"Division of Evolution, Infection and Genomics, University of Manchester, Manchester M13 9PT, UK"},{"name":"Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-2171","authenticated-orcid":true,"given":"Taoran","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Kottara","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, University of Manchester, Manchester M13 9PT, UK"},{"name":"Pathogen Genomics and Virology Laboratory, UKHSA, Manchester M13 9WL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-820X","authenticated-orcid":true,"given":"Michael A.","family":"Brockhurst","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-8256","authenticated-orcid":true,"given":"Rosanna C. T.","family":"Wright","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_3_8_2_2","unstructured":"House of Commons Science Innovation and Technology Committee. 2023 The antimicrobial potential of bacteriophages. 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