Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy
Abstract Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains unclear. Here,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07598-8 |
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| author | Mahmood Almosuli Anna Kirtava Archil Chkhotua Lia Tsveniashvili Nina Chanishvili Sumaiya Safia Irfan Emily Ng Hope McIntyre Adam J. Hockenberry Robyn P. Araujo Weidong Zhou Ngoc Vuong Barbara Birkaya Lance Liotta Alessandra Luchini |
| author_facet | Mahmood Almosuli Anna Kirtava Archil Chkhotua Lia Tsveniashvili Nina Chanishvili Sumaiya Safia Irfan Emily Ng Hope McIntyre Adam J. Hockenberry Robyn P. Araujo Weidong Zhou Ngoc Vuong Barbara Birkaya Lance Liotta Alessandra Luchini |
| author_sort | Mahmood Almosuli |
| collection | DOAJ |
| description | Abstract Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains unclear. Here, we tested the following hypotheses: 1) urinary microbiome phage populations switch to a higher relative proportion of temperate phages, and 2) the activity of the phage recombination machinery (integration/excision/transposition) is higher during human urinary tract infections (UTIs) than in non-infected urinary tracts. Using human urine, model organisms, mass spectrometry, gene expression analysis, and the phage phenotype prediction model BACPHLIP, the results corroborated our hypotheses at the functional protein and gene levels. From a human health perspective, these data suggest that temperate phages may facilitate bacterial infections rather than function as protective agents. These findings support the use of lysogenic phages as therapeutic Trojan Horses. |
| format | Article |
| id | doaj-art-83a1123e10c04c19bde66bc13ddf4a45 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-83a1123e10c04c19bde66bc13ddf4a452025-02-09T12:50:27ZengNature PortfolioCommunications Biology2399-36422025-02-018111310.1038/s42003-025-07598-8Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapyMahmood Almosuli0Anna Kirtava1Archil Chkhotua2Lia Tsveniashvili3Nina Chanishvili4Sumaiya Safia Irfan5Emily Ng6Hope McIntyre7Adam J. Hockenberry8Robyn P. Araujo9Weidong Zhou10Ngoc Vuong11Barbara Birkaya12Lance Liotta13Alessandra Luchini14George Mason UniversityIConsilium Second Medical Opinion, New York CityThe University of GeorgiaIConsilium Second Medical Opinion, New York CityEliava Institute of Bacteriophage, Microbiology & VirologyGeorge Mason UniversityGeorge Mason UniversityLyme Hope, LLCTempus LabsThe University of MelbourneGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityAbstract Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains unclear. Here, we tested the following hypotheses: 1) urinary microbiome phage populations switch to a higher relative proportion of temperate phages, and 2) the activity of the phage recombination machinery (integration/excision/transposition) is higher during human urinary tract infections (UTIs) than in non-infected urinary tracts. Using human urine, model organisms, mass spectrometry, gene expression analysis, and the phage phenotype prediction model BACPHLIP, the results corroborated our hypotheses at the functional protein and gene levels. From a human health perspective, these data suggest that temperate phages may facilitate bacterial infections rather than function as protective agents. These findings support the use of lysogenic phages as therapeutic Trojan Horses.https://doi.org/10.1038/s42003-025-07598-8 |
| spellingShingle | Mahmood Almosuli Anna Kirtava Archil Chkhotua Lia Tsveniashvili Nina Chanishvili Sumaiya Safia Irfan Emily Ng Hope McIntyre Adam J. Hockenberry Robyn P. Araujo Weidong Zhou Ngoc Vuong Barbara Birkaya Lance Liotta Alessandra Luchini Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy Communications Biology |
| title | Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy |
| title_full | Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy |
| title_fullStr | Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy |
| title_full_unstemmed | Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy |
| title_short | Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy |
| title_sort | urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy |
| url | https://doi.org/10.1038/s42003-025-07598-8 |
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