{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:08:10Z","timestamp":1790096890339,"version":"4.0.1"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"37","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515010700"],"award-info":[{"award-number":["2024A1515010700"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2024A03J1057"],"award-info":[{"award-number":["2024A03J1057"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370191"],"award-info":[{"award-number":["32370191"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Carbapenem-resistant Pseudomonas aeruginosa (CR-PA) has been designated a \u201cpriority\u201d pathogen by the World Health Organization, calling for the development of new control strategies. However, no such new drugs are currently available. In this study, we restored bacterial sensitivity to meropenem through a metabolic state-reprogramming approach. Glutamate was identified as the key reprogramming metabolite that converts an antibiotic-resistant metabolic state to an antibiotic-sensitive state in both lab-evolved and clinically isolated CR-PA. This reprogramming leads to increased meropenem uptake, which overcomes drug efflux and enzymatic hydrolysis, elevates intracellular drug concentrations, and restores meropenem killing efficacy in vitro and in vivo. Mechanistically, glutamate metabolic flux enters fatty acid biosynthesis via the pyruvate cycle, elevating lauric acid levels. Increased lauric acid enhances outer membrane permeability, thereby raising intracellular meropenem accumulation. Glutamate is a nutritional amino acid, and the dose used in this study is lower than that in routine clinical use. Collectively, these findings provide an effective, convenient, and economical approach to restore meropenem killing efficacy against CR-PA.<\/jats:p>","DOI":"10.1021\/acsomega.6c07419","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:02:05Z","timestamp":1788890525000},"page":"56406-56418","source":"Crossref","is-referenced-by-count":0,"title":["Glutamate Potentiates\nMeropenem Killing of Carbapenem-Resistant\n                    <i>Pseudomonas aeruginosa<\/i>\n                    by Increasing Outer Membrane\nPermeability to Increase Uptake"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1888-3775","authenticated-orcid":true,"given":"Li-Fen","family":"Yang","sequence":"first","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]},{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Feng","family":"Lai","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Chen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , 135 Xingang Xi Road , Haizhu, ,","place":["Guangzhou, China, 510275"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1808-751X","authenticated-orcid":true,"given":"Jiao","family":"Xiang","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang-Gui","family":"Chen","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]},{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]},{"name":"Third Affiliated Hospital of Sun Yat-sen University , , 600 Tianhe Road , Tianhe, ,","place":["Guangzhou, China, 510630"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026092211031228400_cit1","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/s41579-024-01035-z","article-title":"The Wound Microbiota: Microbial Mechanisms\nof Impaired Wound Healing and Infection","volume":"22","author":"Uberoi","year":"2024","journal-title":"Nat.\nRev. Microbiol."},{"key":"2026092211031228400_cit2","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41579-025-01193-8","article-title":"Pseudomonas aeruginosa: Ecology, Evolution, Pathogenesis and Antimicrobial\nSusceptibility","volume":"23","author":"Letizia","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"2026092211031228400_cit3","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1080\/22221751.2022.2048972","article-title":"Carbapenemase-Producing Pseudomonas aeruginosa - An Emerging Challenge","volume":"11","author":"Tenover","year":"2022","journal-title":"Emerg Microbes Infect."},{"key":"2026092211031228400_cit4","doi-asserted-by":"publisher","first-page":"103159","DOI":"10.1016\/j.jiph.2026.103159","article-title":"Molecular Analysis of Carbapenemase-Producing Pseudomonas aeruginosa Strains in a Tertiary Care Hospital\nin Riyadh","volume":"19","author":"Alshammari","year":"2026","journal-title":"J. Infect. 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Infect."},{"key":"2026092211031228400_cit28","doi-asserted-by":"publisher","first-page":"3790","DOI":"10.1039\/D5CC03871E","article-title":"Synthesis\nand Biological Activity of Potential Retrometabolic\nPolymyxins via Thiol-Ene Chemistry","volume":"62","author":"Smith","year":"2026","journal-title":"Chem. Commun."},{"key":"2026092211031228400_cit29","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1021\/acsinfecdis.3c00480","article-title":"Metabolomics\nMethod in Understanding and Sensitizing Carbapenem-Resistant Acinetobacter baumannii to Meropenem","volume":"10","author":"Li","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"2026092211031228400_cit30","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/s41564-023-01369-z","article-title":"Inhibiting Fatty Acid Synthesis Overcomes Colistin\nResistance","volume":"8","author":"Carfrae","year":"2023","journal-title":"Nat. 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Dis."},{"key":"2026092211031228400_cit41","doi-asserted-by":"publisher","first-page":"0554","DOI":"10.34133\/research.0554","article-title":"Pyruvate Abundance\nConfounds Aminoglycoside Killing of Multidrug-Resistant\nBacteria via Glutathione Metabolism","volume":"7","author":"Xiang","year":"2024","journal-title":"Research"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c07419","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/37\/56406\/68451826\/acsomega.6c07419.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/37\/56406\/68451826\/acsomega.6c07419.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:13:28Z","timestamp":1790093608000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/37\/56406\/5426566\/Glutamate-Potentiates-Meropenem-Killing-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":41,"journal-issue":{"issue":"37","published-online":{"date-parts":[[2026,9,8]]},"published-print":{"date-parts":[[2026,9,22]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c07419","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}