{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:10:10Z","timestamp":1787962210045,"version":"build-2784847793"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The combined use of phages and antibiotics offers an alternative avenue against multidrug-resistant bacteria. We have previously described the synergistic antibacterial effect of the phage pB23 and meropenem combination against carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      (CRAB). The study uncovers the underlying molecular mechanism of phage resistance in CRAB mediated by a novel stop-gain mutation in the gene\n                      <jats:italic toggle=\"yes\">gtr9<\/jats:italic>\n                      . Through phenotypic characterization of pleiotropy, including reduction of capsular polysaccharide production and biofilm formation caused by the mutation in\n                      <jats:italic toggle=\"yes\">gtr9<\/jats:italic>\n                      , we revealed an evolutionary trade-off mechanism whereby phage-resistant CRAB exhibits reduced carbapenem resistance. The zebrafish infection model demonstrated that these phage-resistant mutants were attenuated in virulence\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Throughout continuous passage experiments\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">gtr9<\/jats:italic>\n                      mutants displayed the stability of decreased growth rate, phage resistance, and virulence reduction. The combination therapy between phage pB23 and meropenem in different matrices exhibited consistent synergistic antibacterial activity\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , demonstrating its potential therapeutic\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Collectively, our study reveals a trade-off mechanism underlying phage-antibiotic synergy, thereby providing a novel insight into bacterial resistance evolution and demonstrating the therapeutic potential of this approach against CRAB infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01355-25","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T14:56:44Z","timestamp":1767106604000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Gtr9<\/i>\n                    mutation trades phage resistance for carbapenem sensitivity to potentiate phage-meropenem therapy against\n                    <i>carbapenem-resistant Acinetobacter baumannii in 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