{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:10:25Z","timestamp":1785283825322,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Antibiotic resistance is an increasing concern for human and animal health worldwide. Recently, the concept of reverting bacterial resistance by changing the metabolic state of antibiotic-resistant bacteria has emerged. In this study, we investigated the reversal of Apramycin resistance in <jats:italic>Salmonella<\/jats:italic>. First, non-targeted metabonomics were used to identify key differential metabolites of drug-resistant bacteria. Then, the reversal effect of exogenous substances was verified <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Finally, the underlying mechanism was studied. The results showed that the metabolites citrulline and glutamine were significantly reduced in Apramycin-resistant <jats:italic>Salmonella<\/jats:italic>. When citrulline and glutamine were added to the culture medium of drug-resistant <jats:italic>Salmonella<\/jats:italic>, the killing effect of Apramycin was restored markedly. Mechanistic studies showed that citrulline and glutamine promoted the Tricarboxylic acid cycle, produced more NADH in the bacteria, and increased the proton-motive force, thus promoting Apramycin entry into the bacterial cells, and killing the drug-resistant bacteria. This study provides a useful method to manage infections by antibiotic-resistant bacteria.<\/jats:p>","DOI":"10.3389\/fmicb.2021.759170","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T09:16:36Z","timestamp":1634202996000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Exogenous Citrulline and Glutamine Contribute to Reverse the Resistance of Salmonella to Apramycin"],"prefix":"10.3389","volume":"12","author":[{"given":"Yan","family":"Yong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ijfoodmicro.2014.07.031","article-title":"Characterization of integrons and resistance genes in multidrug-resistant Salmonella enterica isolated from meat and dairy products in Egypt","volume":"189","author":"Ahmed","year":"2014","journal-title":"Int. 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