{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:32:06Z","timestamp":1790897526877,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Canadian Government | Natural Sciences and Engineering Research Council of Canada","award":["2018-05996"],"award-info":[{"award-number":["2018-05996"]}]},{"name":"Farncombe Family Chair in Phage Biology"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,2,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Bacteriophages (phages) are bacterial-specific viruses that can be used alone or with antibiotics to reduce bacterial load. Most phages are unsuitable for therapy because they are \u201ctemperate\u201d and can integrate into the host genome, forming a lysogen that is protected from subsequent phage infections. However, integrated phages can be awakened by stressors such as antibiotics. Supported by this interaction, here we explore the potential use of combined temperate phage and antibiotic against the multi-drug-resistant pathogen,\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              . In all, thirty-nine temperate phages were isolated from clinical strains, and a subset was screened for synergy with six antibiotics (ciprofloxacin, levofloxacin, meropenem, piperacillin, tobramycin, and polymyxin B), using checkerboard assays. Interestingly, our screen identified phages that can synergize with each antibiotic, despite their widely differing targets; however, these are highly phage-antibiotic and phage-host pairing specific. Screening across multiple clinical strains reveals that temperate phages can reduce the antibiotic minimum inhibitory concentration up to 32-fold, even in a resistant isolate, functionally re-sensitizing the bacterium to the antibiotic. Meropenem and tobramycin did not reduce the frequency of lysogens, suggesting a mechanism of action independent of the temperate nature of the phages. By contrast, ciprofloxacin and piperacillin were able to reduce the frequency of lysogeny, the former by inducing phages\u2014as previously reported in\n              <jats:italic>E. coli<\/jats:italic>\n              . Curiously, synergy with piperacillin reduced lysogen survivors, but not by inducing the phages, suggesting an alternative mechanism for biasing the phage lysis-lysogeny equilibrium. Overall, our findings indicate that temperate phages can act as adjuvants in clinically relevant pathogens, even in the presence of antibiotic resistance, thereby drastically expanding their therapeutic potential.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The recent discovery that otherwise therapeutically unusable temperate phages can potentiate the activity of antibiotics, resulting in a potent synergy, has only been tested in\n              <jats:italic>E. coli<\/jats:italic>\n              , and with a single model phage. Here, working with clinical isolates of\n              <jats:italic>Pseudomonas<\/jats:italic>\n              and phages from these isolates, we highlight the broad applicability of this synergy\u2014across a variety of mechanisms but also highlight the limitations of predicting the phage, host, and antibiotic combinations that will synergize.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02559-24","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T14:00:36Z","timestamp":1734703236000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Temperate phage-antibiotic synergy is widespread\u2014extending to\n            <i>Pseudomonas<\/i>\n            \u2014but varies by phage, host strain, and antibiotic pairing"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6590-3311","authenticated-orcid":false,"given":"Rabia","family":"Fatima","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7058-6006","authenticated-orcid":true,"given":"Alexander P.","family":"Hynes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]},{"name":"Department of Medicine, McMaster University","place":["Hamilton, Canada"]},{"name":"Farncombe Family Digestive Health Research Institute, McMaster University","place":["Hamilton, Canada"]},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","first-page":"277","article-title":"The antibiotic resistance crisis:part 1:causes and threats","volume":"40","author":"Ventola CL","year":"2015","unstructured":"Ventola CL. 2015. The antibiotic resistance crisis:part 1:causes and threats. 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