{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:00:59Z","timestamp":1778119259320,"version":"3.51.4"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"42","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,10,17]]},"abstract":"<jats:p>\n            <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n            exploits host-derived phosphatidylcholine (PC) to establish persistent lung infections, yet the mechanistic link between metabolic adaptation and pathogenesis remains unclear. Here, we demonstrate that choline (Cho)\u2013induced regulator (CodR), a GcvA-type transcriptional regulator, serves as a master regulator integrating virulence, antibiotic resistance, and PC catabolism during pulmonary infection. CodR directly binds Cho, the key metabolite of PC degradation, to activate\n            <jats:italic toggle=\"yes\">pchP<\/jats:italic>\n            and\n            <jats:italic toggle=\"yes\">norA<\/jats:italic>\n            , facilitating exogenous PC\/Cho utilization. Genome-wide profiling reveals that CodR targets conserved motifs in promoters of\n            <jats:italic toggle=\"yes\">mexA<\/jats:italic>\n            ,\n            <jats:italic toggle=\"yes\">pslA<\/jats:italic>\n            , and\n            <jats:italic toggle=\"yes\">amrZ<\/jats:italic>\n            , synchronizing virulence and tolerance pathways.\n            <jats:italic toggle=\"yes\">codR<\/jats:italic>\n            deletion attenuated biofilm formation, type III secretion system activity, siderophore production, and PC catabolism, reducing bacterial pathogenicity in a murine pneumonia model. Notably, Cho\/PC pretreatment potentiates CodR-dependent transcriptional activation of antibiotic resistance genes, elevating tolerance to ciprofloxacin and meropenem. Our findings elucidate a paradigm wherein\n            <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n            co-opts host-derived Cho via CodR to simultaneously potentiate virulence and antibiotic resilience, exposing CodR as a druggable node to break infection-resistance synergies.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adz1415","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:58:56Z","timestamp":1760723936000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["A choline-sensing regulator coordinates metabolic adaptation and pathogenesis in\n            <i>Pseudomonas aeruginosa<\/i>\n            pulmonary infections"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-2364","authenticated-orcid":true,"given":"Yingjie","family":"Song","sequence":"first","affiliation":[{"name":"College of Life Science, Sichuan Normal 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Chengdu 610041, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derong","family":"Dai","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-3600","authenticated-orcid":true,"given":"Qinqin","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Life Science, Sichuan Normal University, Chengdu 610101, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-8716","authenticated-orcid":true,"given":"Rui","family":"Bao","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, 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