{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:46:38Z","timestamp":1791477998029,"version":"4.3.4"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Provincial Health Commission Bureau Foundation of Jiangxi","award":["202310600"],"award-info":[{"award-number":["202310600"]}]},{"name":"Provincial Health Commission Bureau Foundation of Jiangxi","award":["202310013"],"award-info":[{"award-number":["202310013"]}]},{"name":"Provincial Administration of Traditional Chinese Medicine science and technology plan key project of Jiangxi","award":["2022Z030"],"award-info":[{"award-number":["2022Z030"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272340"],"award-info":[{"award-number":["82272340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"General Project of Nanjing Municipal Health Commission Bureau","award":["YKK22131"],"award-info":[{"award-number":["YKK22131"]}]},{"name":"Talent Lift Foundation of the Second Hospital of Nanjing","award":["RCMS24005"],"award-info":[{"award-number":["RCMS24005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Acinetobacter baumannii bacteremia caused by pandrug-resistant strains poses a major challenge in intensive care units, necessitating novel therapeutic approaches. Phage-derived depolymerases offer a promising adjunct to conventional antibiotics. However, studies on A. baumannii phage depolymerases have been limited to non-mammalian models. This study investigates the therapeutic efficacy, safety, and potential mechanisms of action of DPO-HL, both as a monotherapy and in combination with polymyxin B, in a murine model of A. baumannii bacteremia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>DPO-HL was expressed and purified via Ni-NTA affinity chromatography. Its bactericidal activity was assessed through dynamic killing and biofilm disruption assays. Interaction with human plasma was examined to determine its impact on plasma\u2019s bactericidal activity. Synergy with polymyxin B was evaluated by MIC reduction. Safety was assessed via cytotoxicity, haemolysis, and acute toxicity tests. A mouse bacteremia model was established to evaluate therapeutic efficacy via intraperitoneal and intravenous administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>DPO-HL, targeting KL160 capsular polysaccharide, exhibited stability in plasma and enhanced plasma\u2019s bactericidal effect. It showed strong synergy with polymyxin B, reducing its MIC by 16-fold, and efficiently eradicated mature biofilms. DPO-HL alone reduced bacterial load and endotoxin levels but rescued only 30% of bacteremia mice. Combination therapy (1.45\u2005mg\/kg DPO-HL\u200a+\u200a0.5\u2005mg\/kg polymyxin B) significantly reduced endotoxin levels and achieved 100% survival, regardless of administration route.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study identifies a KL160-targeting depolymerase and demonstrates its potent synergy with polymyxin B in treating A. baumannii bacteremia, supporting its potential for clinical application.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf110","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T16:43:21Z","timestamp":1744217001000},"page":"1613-1625","source":"Crossref","is-referenced-by-count":3,"title":["Depolymerase as a potent adjunct to polymyxin for targeting KL160 pandrug-resistant <i>Acinetobacter baumannii<\/i> in a murine bacteremia model"],"prefix":"10.1093","volume":"80","author":[{"given":"Bai-Ling","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion, The Second Affiliated Hospital of Nanchang University , Nanchang 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, The Second Affiliated Hospital of Nanchang University , Nanchang 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]},{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Le","family":"Xiong","sequence":"additional","affiliation":[{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Hu","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Cheng","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, The Second Affiliated Hospital of Nanchang University , Nanchang 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Jiangxi Provincial People\u2019s Hospital , No. 92, Aiguo Road, Donghu District, Nanchang 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Han","family":"Gao","sequence":"additional","affiliation":[{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du-Xian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2352-4351","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 ,","place":["China"]},{"name":"Clinical Research Center, The Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine , Nanjing 210003 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