{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:28:42Z","timestamp":1790227722753,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["I53C22001300001"],"award-info":[{"award-number":["I53C22001300001"]}]},{"name":"Italian Ministry of Health","award":["I53C22000780001"],"award-info":[{"award-number":["I53C22000780001"]}]},{"name":"PNRR THE e Tuscany Health Ecosystem","award":["I53C22001300001"],"award-info":[{"award-number":["I53C22001300001"]}]},{"name":"PNRR THE e Tuscany Health Ecosystem","award":["I53C22000780001"],"award-info":[{"award-number":["I53C22000780001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Pseudomonas aeruginosa is a major opportunistic pathogen with high levels of antibiotic resistance. Phage therapy represents a promising alternative for the treatment of difficult infections both alone and in combination with antibiotics. Here, we isolated and characterized three novel lytic myoviruses, Cisa, Nello, and Moonstruck. Genomic analysis revealed that Cisa and Nello belong to the Pbunavirus genus, while Moonstruck is a novel Pakpunavirus species. All lacked lysogeny, virulence, or resistance-associated genes, supporting their therapeutic suitability. Phage Nello and Moonstruck were active against P. aeruginosa Pa3GrPv, isolated from a patient with lung infection candidate for phage therapy. Moonstruck exhibited superior lytic activity with ciprofloxacin sub-MIC value (0.125 \u00b5g\/mL), achieving bacterial suppression for 48 h. However, to improve the lytic efficacy of the phages on the clinical isolate, phage adaptation via serial passage was investigated. The killing efficacy of Nello was enhanced, whereas Moonstruck showed a less consistent improvement, suggesting phage-specific differences in evolutionary dynamics. Sequencing of the evolved phages revealed point mutations in tail-associated genes, potentially linked to a better phage\u2013host interaction. These results support the use of phage\u2013antibiotic combinations and directed evolution as strategies to enhance phage efficacy against drug-resistant infections. Overall, these findings support the therapeutic potential of the newly isolated phages in treating P. aeruginosa lung infections.<\/jats:p>","DOI":"10.3390\/v17070938","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic Optimization of Pseudomonas aeruginosa Phages: From Isolation to Directed Evolution"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4574-4512","authenticated-orcid":false,"given":"Sara","family":"Bolognini","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"},{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Ferretti","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7362-6117","authenticated-orcid":false,"given":"Claudia","family":"Campobasso","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Trovato","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-4976","authenticated-orcid":false,"given":"Magda","family":"Marchetti","sequence":"additional","affiliation":[{"name":"National Centre for Innovative Technologies in Public Health, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7036-1192","authenticated-orcid":false,"given":"Laura","family":"Rindi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5791-686X","authenticated-orcid":false,"given":"Arianna","family":"Tavanti","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-034X","authenticated-orcid":false,"given":"Mariagrazia","family":"Di Luca","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2022.11.017","article-title":"Phage Therapy: From Biological Mechanisms to Future Directions","volume":"186","author":"Strathdee","year":"2023","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ruekit, S., Srijan, A., Serichantalergs, O., Margulieux, K.R., Mc Gann, P., Mills, E.G., Stribling, W.C., Pimsawat, T., Kormanee, R., and Nakornchai, S. 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