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Bacteriophages that can kill bacteria inside host cells have been identified for pathogens including\n            <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n            ,\n            <jats:italic toggle=\"yes\">Mycobacterium<\/jats:italic>\n            , and\n            <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n            species. Even in pathogens for which no stable phages have been isolated, such as\n            <jats:italic toggle=\"yes\">Legionella pneumophila<\/jats:italic>\n            , the presence of phage defense systems suggests phage susceptibility. Here, we report the stable isolation of\n            <jats:italic toggle=\"yes\">Legionella<\/jats:italic>\n            bacteriophage LME-1 (\n            <jats:italic toggle=\"yes\">Legionella<\/jats:italic>\n            mobile element\u20131) and its impact on bacterial virulence in humans. Cryo\u2013electron microscopy of the capsid (2.1 angstroms) and portal-tail complex (1.9 angstroms) reveals an unambiguous phage particle with T7-like morphology. Characterizing the host range of this phage, we make a serendipitous finding that links the acquisition of a phage defense mechanism to the formation of a virulent clade of\n            <jats:italic toggle=\"yes\">L. pneumophila<\/jats:italic>\n            responsible for 80% of all Legionnaires\u2019 disease.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adx9722","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:58:46Z","timestamp":1756922326000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["The discovery of a\n            <i>Legionella<\/i>\n            phage explains a key determinant of human disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6586-5121","authenticated-orcid":true,"given":"Beth","family":"Nicholson","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0983-0816","authenticated-orcid":true,"given":"Jos\u00e9 F.","family":"Sant\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."},{"name":"Department of Molecular Genetics, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2031-0942","authenticated-orcid":true,"given":"Elizabeth H.","family":"Chaney","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8811-9871","authenticated-orcid":true,"given":"Justin C.","family":"Deme","sequence":"additional","affiliation":[{"name":"Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Boyles Street, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1234-1123","authenticated-orcid":true,"given":"Shayna R.","family":"Deecker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4356-1942","authenticated-orcid":true,"given":"Kristina","family":"Sztanko","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-9199","authenticated-orcid":true,"given":"Alan R.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."},{"name":"Department of Molecular Genetics, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-8053","authenticated-orcid":true,"given":"Susan M.","family":"Lea","sequence":"additional","affiliation":[{"name":"Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Boyles Street, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0824-3704","authenticated-orcid":true,"given":"Alexander W.","family":"Ensminger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."},{"name":"Department of Molecular Genetics, University of Toronto, 661 University Ave., Toronto, Ontario M5G 1M1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.33.12.1179"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)10041-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.1.20-28.2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2017.22.27.30566"},{"key":"e_1_3_2_6_2","unstructured":"P. Shah A. Barskey A. Binder C. Edens S. Lee J. Smith S. Schrag C. Whitney L. 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Cheng asarnow\/pyem: UCSF pyem v0.5 version v0.5 Zenodo (2019); https:\/\/doi.org\/10.5281\/zenodo.3576630."},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1399004714021683"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798318006551"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3330"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1019"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1203-980"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adx9722","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:59:25Z","timestamp":1756922365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adx9722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":67,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2025,9,5]]}},"alternative-id":["10.1126\/sciadv.adx9722"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adx9722","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]},"assertion":[{"value":"2025-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx9722"}}