{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:23:55Z","timestamp":1779236635651,"version":"3.51.4"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014764","name":"China Medical Foundation","doi-asserted-by":"crossref","award":["2024CMFA04"],"award-info":[{"award-number":["2024CMFA04"]}],"id":[{"id":"10.13039\/501100014764","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Life Oasis Public Service Center","award":["CPHCF-ZLKY-20241114"],"award-info":[{"award-number":["CPHCF-ZLKY-20241114"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Carbapenem-resistant (CR) organisms (CRO) have been identified as critical priority pathogens, emphasizing the urgent need for novel therapeutic strategies. Combination therapy emerges as a promising approach to address multidrug-resistant bacterial infections. Here we demonstrate that eravacycline (ERV), in combination with amikacin (AMK), effectively eliminates a panel of clinically isolated CR\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , CR\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , and CR\n                    <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    . Mechanistically, the AMK-ERV combination enhances bacterial oxidative phosphorylation, leading to an accumulation of reactive oxygen species, which induce oxidative stress and accelerate bacterial cell death. Notably, this combination significantly improves survival rates in mouse models of intra-abdominal infection, demonstrating efficacy against infections induced by CR pathogens. Furthermore, serum metabolomics reveals that the AMK-ERV combination upregulates metabolic pathways of lipids and amino acids. Interestingly, the amino acid methionine significantly enhances the antibacterial activity of ERV against CR pathogens both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Our findings underscore the potential of repurposing AMK in combination with ERV to combat CR pathogens and propose a novel strategy for controlling these infections through the combination of antibiotics with specific metabolites such as methionine.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013938","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:32:26Z","timestamp":1770748346000},"page":"e1013938","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amikacin-eravacycline combination mediates the synergistic elimination of carbapenem-resistant pathogens via in vitro and in vivo metabolic reprogramming"],"prefix":"10.1371","volume":"22","author":[{"given":"Xiaoli","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yili","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinmei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaying","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tinghua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yougang","family":"Mai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9354-9128","authenticated-orcid":true,"given":"Xikang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"issue":"6","key":"ppat.1013938.ref001","first-page":"429","article-title":"Antimicrobial resistance: it is a global crisis, \u201ca slow tsunami\u201d","volume":"75","author":"C Capozzi","year":"2019","journal-title":"Ig Sanita Pubbl"},{"key":"ppat.1013938.ref002","first-page":"101111","article-title":"Antimicrobial resistance in China across human, animal, and environment sectors - a review of policy documents using a governance framework","volume":"48","author":"D Yang","year":"2024","journal-title":"Lancet Reg Health West Pac"},{"key":"ppat.1013938.ref003","doi-asserted-by":"crossref","first-page":"177461","DOI":"10.1016\/j.scitotenv.2024.177461","article-title":"Transmission and control strategies of antimicrobial resistance from the environment to the clinic: A holistic review","volume":"957","author":"S Yuan","year":"2024","journal-title":"Sci Total Environ"},{"key":"ppat.1013938.ref004","doi-asserted-by":"crossref","unstructured":"GBD 2021 Antimicrobial Resistance Collaborators. 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