{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:24:44Z","timestamp":1790529884379,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930115, 31902414"],"award-info":[{"award-number":["31930115, 31902414"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Bacterial metabolism is related to resistance and susceptibility to antibiotics. Fumarate and nitrate reduction regulatory protein (FNR) is a global transcriptional regulator that regulates metabolism. However, the role of FNR in antibiotic resistance is elusive. Here, <jats:italic>fnr<\/jats:italic> deletion mutant was constructed and used to test the role in <jats:italic>Edwardsiella tarda<\/jats:italic> EIB202 (EIB202). \u0394<jats:italic>fnr<\/jats:italic> exhibited elevated sensitivity to aminoglycosides. The mutant had a globally enhanced metabolome, with activated alanine, aspartate, and glutamate metabolism and increased abundance of glutamic acid as the most impacted pathway and crucial biomarker, respectively. Glutamate provides a source for the pyruvate cycle (the P cycle) and thereby relationship between exogenous glutamate-activated P cycle and gentamicin-mediated killing was investigated. The activated P cycle elevated proton motive force (PMF). Consistently, exogenous glutamate potentiated gentamicin-mediated killing to EIB202 as the similarity as the loss of FNR did. These findings reveal a previously unknown regulation by which FNR downregulates glutamate and in turn inactivates the P cycle, which inhibits PMF and thereby exhibits the resistance to aminoglycosides.<\/jats:p>","DOI":"10.3389\/fmicb.2022.1003586","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T07:23:32Z","timestamp":1662535412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Global transcriptional regulator FNR regulates the pyruvate cycle and proton motive force to play a role in aminoglycosides resistance of Edwardsiella tarda"],"prefix":"10.3389","volume":"13","author":[{"given":"Li-Chun","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan-Xian","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature10069","article-title":"Metabolite-enabled eradication of bacterial persisters by aminoglycosides","volume":"473","author":"Allison","year":"2011","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e02526","DOI":"10.1128\/AEM.02526-17","article-title":"An attenuated salmonella enterica serovar Typhimurium strain and galacto-oligosaccharides accelerate clearance of salmonella infections in poultry through modifications to the gut microbiome","volume":"84","author":"Azcarate-Peril","year":"2018","journal-title":"Appl. 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