{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:05:27Z","timestamp":1781082327140,"version":"3.54.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Zhejiang Provincial Public Welfare Technology Program of China","award":["LGF22H190003"],"award-info":[{"award-number":["LGF22H190003"]}]},{"name":"Natural Science Fund of Ningbo","award":["202003N4267"],"award-info":[{"award-number":["202003N4267"]}]},{"name":"HwaMei Research Foundation of Ningbo No.2 Hospital","award":["2025HM03"],"award-info":[{"award-number":["2025HM03"]}]},{"name":"Ningbo Key Laboratory of Multimodal Intelligent Detection and Translational Research for Major Diseases"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2026HMG063"],"award-info":[{"award-number":["2026HMG063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pseudomonas aeruginosa is a major nosocomial pathogen, and its antibiotic tolerance under low-metabolism conditions severely compromises clinical efficacy, presenting a significant therapeutic challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>A quantitative assessment of the metabolic dependence of clinically relevant antibiotics against P. aeruginosa was conducted, and a novel combination strategy capable of eradicating its low-metabolic populations was developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a gradient nutrient model (0%\u2013100% LB) to simulate a continuum of metabolic states. Through linear regression analysis correlating ATP levels with bactericidal efficiency, we developed a Metabolic Dependence Index classification system. Leveraging this system, we designed a Strongly Metabolism-Dependent (SMD)\u200a+\u200aWeakly Metabolism-Dependent (WMD) synchronous combination strategy, which was subsequently validated using five clinical isolates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Low-metabolism populations exhibited significantly reduced susceptibility to SMD agents but unaltered tolerance to WMD antibiotics. The SMD\u200a+\u200aWMD combination achieved enhanced killing of low-metabolism bacteria (&amp;gt;99.999% killing) with a marked dose reduction in vitro. This strategy also improved in vitro clearance efficacy compared to monotherapy. Collectively, our work provides a quantitative framework for targeting metabolic heterogeneity to overcome antibiotic tolerance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag204","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T11:22:12Z","timestamp":1780312932000},"source":"Crossref","is-referenced-by-count":0,"title":["Harnessing metabolic dependence-driven antibiotic synergy to eradicate tolerant\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1093","volume":"81","author":[{"given":"Yuanye","family":"Ji","sequence":"first","affiliation":[{"name":"Centre for Medical Research, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Tuo","sequence":"additional","affiliation":[{"name":"Centre for Medical Research, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Ruan","sequence":"additional","affiliation":[{"name":"Centre for Medical Research, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Centre for Medical Research, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fajiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery Dept.1, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Centre for Medical Research, Ningbo No.2 Hospital , Ningbo City, Zhejiang Province ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"2026061004552037500_dkag204-B1","doi-asserted-by":"publisher","first-page":"16497","DOI":"10.1038\/s41598-021-95852-4","article-title":"Association between mortality and highly antimicrobial-resistant bacteria in intensive care unit-acquired pneumonia","volume":"11","author":"Lakbar","year":"2021","journal-title":"Sci Rep"},{"key":"2026061004552037500_dkag204-B2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jhin.2024.03.009","article-title":"Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to 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