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Its ability to colonize and persist in diverse niches is attributed to its large accessory genome, where prophages represent a common feature and may contribute to its fitness and persistence. We focused on the CF airways niche and used 197 longitudinal isolates from 12 patients persistently infected by P. aeruginosa. We computationally predicted intact prophages for each longitudinal group and scored their long-term persistence. We then confirmed prophage inducibility and mapped their location in the host chromosome with lysate sequencing. Using comparative genomics, we evaluated prophage genomic diversity, long-term persistence, and level of genomic maintenance. Our findings support previous findings that most P. aeruginosa genomes harbour prophages some of which can self-induce, and that a common CF-treating antibiotic, ciprofloxacin, can induce prophages. Induced prophage genomes displayed high diversity and even genomic novelty. Finally, all induced prophages persisted long-term with their genomes avoiding gene loss and degradation over 4 years of host replication in the stressful CF airways niche. This and our detection of phage genes, which contribute to host competitiveness and adaptation, lends support to our hypothesis that the vast majority of prophages detected as intact and inducible in this study facilitated their host fitness and persistence.<\/jats:p>","DOI":"10.1093\/femsle\/fnaf017","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T22:54:13Z","timestamp":1738364053000},"source":"Crossref","is-referenced-by-count":5,"title":["<i>Pseudomonas aeruginosa<\/i> maintains an inducible array of novel and diverse prophages over lengthy persistence in cystic fibrosis lungs"],"prefix":"10.1093","volume":"372","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-8245","authenticated-orcid":false,"given":"Ifigeneia","family":"Kyrkou","sequence":"first","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Food Safety and Zoonosis, University of Copenhagen , 1870 Frederiksberg ,","place":["Denmark"]},{"name":"The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , 2800 Kgs. Lyngby ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Bartell","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Lechuga","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Technology, Department of Biosystems, KU Leuven , 3001 Heverlee ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9dric","family":"Lood","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Technology, Department of Biosystems, KU Leuven , 3001 Heverlee ,","place":["Belgium"]},{"name":"Laboratory of Computational Systems Biology, Department of Microbial and Molecular Systems, KU Leuven , 3001 Heverlee ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-3173","authenticated-orcid":false,"given":"Rasmus L","family":"Marvig","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-1314","authenticated-orcid":false,"given":"Rob","family":"Lavigne","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Technology, Department of Biosystems, KU Leuven , 3001 Heverlee ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Molin","sequence":"additional","affiliation":[{"name":"The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , 2800 Kgs. 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