{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:19:47Z","timestamp":1792225187803,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/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":["2022A1515220008"],"award-info":[{"award-number":["2022A1515220008"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170014"],"award-info":[{"award-number":["82170014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The global prevalence of carbapenem\u2010resistant\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    <\/jats:styled-content>\n                    (CRAB) represents a substantial concern for public health. Exogenous adenosine triphosphate (ATP) affects the bactericidal efficacy of meropenem against CRAB; however, the precise mechanism remains elusive. Here, reprogramming metabolomics was employed to delve into the mechanism underlying ATP\u2010potentiated meropenem lethality against CRAB. Our findings reveal that ATP reprogramming activates the tricarboxylic acid (TCA) cycle in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>A. baumannii<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Notably, the TCA cycle inhibitor malonate antagonised the synergistic bactericidal effect of ATP and meropenem. Activation of the TCA cycle stimulated riboflavin metabolism pathway and the electron transport chain, leading to increased reactive oxygen species (ROS) production. Hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) enhanced meropenem\u2010mediated killing of CRAB, while the ROS scavenger \u03b1\u2010tocopherol diminished the ATP\u2010potentiated bactericidal effect. Additionally, ATP upregulated the gene expression of outer membrane porins, including\n                    <jats:italic>omp33\u201036<\/jats:italic>\n                    ,\n                    <jats:italic>oprD<\/jats:italic>\n                    ,\n                    <jats:italic>ompW<\/jats:italic>\n                    , and\n                    <jats:italic>ompA<\/jats:italic>\n                    , thereby improving membrane permeability and elevating intracellular levels of meropenem. The therapeutic synergy of ATP with meropenem was validated in a mouse model of acute pneumonia. This study not only highlights the potential of ATP as a co\u2010treatment with meropenem but also elucidates the mechanisms by which ATP reverses CRAB resistance, specifically through the promotion of ROS production and enhanced membrane permeability.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70199","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T15:09:16Z","timestamp":1753110556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synergy of ATP and Meropenem in Stimulating the TCA Cycle to Enhance Killing of Carbapenem\u2010Resistant\n                    <i>Acinetobacter baumannii<\/i>"],"prefix":"10.1111","volume":"18","author":[{"given":"Xia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyun","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlei","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Sun Yat\u2010sen University, Institute of Respiratory Diseases of Sun 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