{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:52:38Z","timestamp":1791381158819,"version":"4.3.3"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI177997, R01AI165997, R01AI148560"],"award-info":[{"award-number":["R01AI177997, R01AI165997, R01AI148560"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL167828"],"award-info":[{"award-number":["R01HL167828"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG056939"],"award-info":[{"award-number":["R01AG056939"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Nosocomial\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      infections are among the most challenging infections to treat, and resistance to last-line agents, including polymyxins and aztreonam-based therapies, risks a future with limited or no clinical treatment options. Bacteriophages (phages) have emerged as a promising therapeutic option, both in cocktails and when given in combination with antibiotics. In this study, we show that the synergy between a lipopolysaccharide (LPS)-specific phage and antibiotics is driven by clinically relevant increases in beta-lactam permeability due to the selection of phage-resistant subpopulations. First, in the Hollow Fiber Infection Model (HFIM), we show that the combination of phage LUZ19 (pili-targeted), phage E215 (LPS-specific), and aztreonam (ATM) eradicated the laboratory host PAO1, whereas monotherapy with neither phage nor ATM could eradicate PAO1. Static time-kill studies (STKS) evaluated the LPS-specific phage PYO2 in combination with either aztreonam\/avibactam (ATM\/AVI) or polymyxin B (PMB) against an extensively drug-resistant clinical isolate of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      (AR-0231). PYO2 combined with ATM\/AVI was determined to be synergistic, with a mean excess-over-bliss (EOB) of 0.350 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05), while PYO2 with PMB was also synergistic, with a mean EOB of 0.361 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). Linear regression of STKS using sequential administration showed that, compared to antibiotic-first treatment, phage-first treatment reduced bacterial concentrations at 24 h by \u22126.19 log\n                      <jats:sub>10<\/jats:sub>\n                      colony-forming unit (CFU)\/mL (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05), with statistically significant interactions estimated for each antibiotic. These results indicated that bacterial pre-selection by PYO2 improved antibiotic activity. Mass spectrometry studies showed that the PYO2-resistant AR-0231 strain exhibited a &gt;25% increase in the outer membrane permeability surface area coefficient for all major anti-\n                      <jats:italic toggle=\"yes\">Pseudomonal<\/jats:italic>\n                      beta-lactams, including aztreonam. Altogether, our study provides mechanistic insights into phage-induced collateral sensitivity of beta-lactams. These results show how specific beta-lactams can be prioritized and optimized in phage-antibiotic combinations to maximize the antibacterial activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00048-26","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:07:46Z","timestamp":1788444466000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Phage-first treatment results in subpopulation-driven collateral sensitivity to beta-lactams in an extensively drug-resistant\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"70","author":[{"given":"Claire","family":"Han","sequence":"first","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob T.","family":"Sanborn","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1069-1720","authenticated-orcid":true,"given":"Thomas D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack F.","family":"Klem","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9229-4131","authenticated-orcid":true,"given":"Brian M.","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-5224","authenticated-orcid":true,"given":"Patrick D.","family":"Kenney","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-8511","authenticated-orcid":true,"given":"Troy D.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Arts and Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2069-8915","authenticated-orcid":true,"given":"Dwayne R.","family":"Roach","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0264fdx42","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, San Diego State University","place":["San Diego, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-2235","authenticated-orcid":true,"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0212-2787","authenticated-orcid":true,"given":"Nicholas M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Clinical and 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