{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:15:28Z","timestamp":1784956528460,"version":"3.55.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01 HL148184-01, R01 AI12492093, R01 DC019965"],"award-info":[{"award-number":["R01 HL148184-01, R01 AI12492093, R01 DC019965"]}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["BURGEN23G0, BURGEN24A0-KB"],"award-info":[{"award-number":["BURGEN23G0, BURGEN24A0-KB"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SU | Stanford Bio-X"},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SU | Stanford Bio-X"},{"name":"HHS | National Institutes of Health","award":["1K23HL169902-01"],"award-info":[{"award-number":["1K23HL169902-01"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2025,3,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Lysogenic bacteriophages can integrate their genome into the bacterial chromosome in the form of a prophage and can promote genetic transfer between bacterial strains\n                      <jats:italic>in vitro<\/jats:italic>\n                      . However, the contribution of lysogenic bacteriophages to the incidence of antimicrobial resistance (AMR) in clinical settings is poorly understood. Here, in a set of 186 clinical isolates of\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      collected from respiratory cultures from 82 patients with cystic fibrosis, we evaluate the links between prophage counts and both genomic and phenotypic resistance to six anti-pseudomonal antibiotics: tobramycin, colistin, ciprofloxacin, meropenem, aztreonam, and piperacillin\u2013tazobactam. We identified 239 different prophages in total. We find that\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      isolates contain on average 3.06 \u00b1 1.84 (SD) predicted prophages. We find no significant association between the number of prophages per isolate and the minimum inhibitory concentration for any of these antibiotics. We then investigate the relationship between particular prophages and AMR. We identify a single lysogenic phage associated with phenotypic resistance to the antibiotic tobramycin and, consistent with this association, we observe that AMR genes associated with resistance to tobramycin are more likely to be found when this prophage is present. However, we find that they are not encoded directly on prophage sequences. Additionally, we identify a single prophage statistically associated with ciprofloxacin resistance but do not identify any genes associated with ciprofloxacin phenotypic resistance. These findings suggest that prophages are only infrequently associated with the AMR genes in clinical isolates of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Antibiotic-resistant infections of\n                        <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                        (\n                        <jats:italic>Pa<\/jats:italic>\n                        ), a leading pathogen in patients with cystic fibrosis (CF), are a global health threat. While lysogenic bacteriophages are known to facilitate horizontal gene transfer, their role in promoting antibiotic resistance in clinical settings remains poorly understood. In our analysis of 186 clinical isolates of\n                        <jats:italic>P. aeruginosa<\/jats:italic>\n                        from CF patients, we find that prophage abundance does not predict phenotypic resistance to key antibiotics but that specific prophages are infrequently associated with tobramycin resistance genes. In addition, we do not find antimicrobial resistance (AMR) genes encoded directly on prophages. These results highlight that while phages can be associated with AMR, phage-mediated AMR transfer may be rare in clinical isolates and difficult to identify. This work is important for future efforts on mitigating AMR in CFCF and other vulnerable populations affected by\n                        <jats:italic>Pa<\/jats:italic>\n                        infections and advances our understanding of bacterial-phage dynamics in clinical infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00904-24","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T09:03:06Z","timestamp":1739437386000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Prophages are infrequently associated with antibiotic resistance in\n                    <i>Pseudomonas aeruginosa<\/i>\n                    clinical isolates"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-6163","authenticated-orcid":false,"given":"Tony H.","family":"Chang","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6939-2909","authenticated-orcid":true,"given":"Julie D.","family":"Pourtois","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi L.","family":"Haddock","sequence":"additional","affiliation":[{"name":"University of California San Francisco Medical School","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate E.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek F.","family":"Amanatullah","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Stanford Hospital and Clinics","place":["Redwood City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Burgener","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology and Sleep Medicine, Children\u2019s Hospital Los Angeles, Keck School of Medicine at USC","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Milla","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Clinic, Department of Medicine, Lucille Packard Children\u2019s Hospital, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-3000","authenticated-orcid":true,"given":"Niaz","family":"Banaei","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Bollyky","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2013.02.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00088-17"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2011.00277.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/1574-6976.12067"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04710-22"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01108"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.24022"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.64.5.679-699.1952"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/41.1.142"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1235"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2014.09.010"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2016.90"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01851-22"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2019.02.008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00016-10"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.32"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13333"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00446-14"},{"key":"e_1_3_3_20_2","volume-title":"Modern genetic analysis: integrating genes and genomes","author":"Griffith AJF","year":"2002","unstructured":"Griffith AJF, Gelbart WM, Lewontin RC, Miller JH. 2002. Modern genetic analysis: integrating genes and genomes. 2nd ed. W. H. Freeman, New York, NY.","edition":"2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007878"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0147-619x(85)90052-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/26.1.131"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5MD00344J"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi5000564"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-27723-z"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.5.3012-3015.2006"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.102"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-020-00867-0"}],"container-title":["mSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00904-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00904-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T11:21:39Z","timestamp":1742901699000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msphere.00904-24"}},"subtitle":[],"editor":[{"given":"Paul D.","family":"Fey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,25]]}},"alternative-id":["10.1128\/msphere.00904-24"],"URL":"https:\/\/doi.org\/10.1128\/msphere.00904-24","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.06.02.595912","asserted-by":"object"}]},"ISSN":["2379-5042"],"issn-type":[{"value":"2379-5042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,25]]},"assertion":[{"value":"2024-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00904-24"}}