{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T20:14:53Z","timestamp":1767816893412,"version":"3.49.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2022-67015-36339"],"award-info":[{"award-number":["2022-67015-36339"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2024-70007-43550"],"award-info":[{"award-number":["2024-70007-43550"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The rise of multidrug-resistant (MDR) pathogens in aquaculture poses a significant threat to food safety and public health by facilitating the transfer of resistance across the food chain, underscoring the need for sustainable, non-antibiotic control measures. Trans-cinnamaldehyde (TC), a phytochemical with antimicrobial activity, is a promising alternative. While previous publications have established the antibacterial efficacy of TC against\n                    <jats:italic>Edwardsiella ictaluri<\/jats:italic>\n                    , the agent of enteric septicemia of catfish, its mechanism of action and the potential for bacterial adaptation after prolonged exposure remain undefined. Here, we addressed these gaps by investigating the antibacterial mechanism, the adaptive response of\n                    <jats:italic>E. ictaluri<\/jats:italic>\n                    to TC, and the vaccine potential of TC-adapted strains, with relevance to One-Health. The minimum inhibitory concentration (MIC) of TC against\n                    <jats:italic>E. ictaluri<\/jats:italic>\n                    was 120 \u00b5g\/mL, whereas 16 \u00b5g\/mL was not inhibitory and was used for long-term adaptation. Serial passages for 30 and 60 days generated D30- and D60-adapted strains. Disk diffusion assays indicated reduced susceptibility to TC and florfenicol but increased susceptibility to sulfamethoxazole\/trimethoprim (SXT) in adapted strains. Virulence assays in catfish fingerlings (three tanks containing 10 fish per tank) demonstrated that D30-TC and D60-TC strains were highly attenuated. Moreover, vaccination with these strains conferred significant protection against wild-type challenge (63.64% and 73.64% survival compared to 20% in controls). Quantitative proteomics revealed the upregulation of multidrug efflux pumps and stress adaptation proteins and the downregulation of central metabolic pathways during TC exposure. Long-term adaptation was characterized by metabolic reprogramming, including enhanced energy and carbohydrate metabolism and suppression of virulence-associated secretion systems. Comparative genomics of D30-TC and D60-TC strains revealed shared mutations in genes related to membrane biosynthesis, energy metabolism, stress response, and regulatory pathways. Together, these findings highlight the potential of TC as an antimicrobial and a potential source of live-attenuated vaccine, while revealing adaptive mechanisms that may inform future strategies for controlling\n                    <jats:italic>E. ictaluri<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0340053","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T19:18:09Z","timestamp":1767813489000},"page":"e0340053","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation mechanisms of action and resistance of Edwardsiella ictaluri to trans-cinnamaldehyde"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2439-0659","authenticated-orcid":true,"given":"Hossam","family":"Abdelhamed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munshi Mustafiz","family":"Riman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-3052","authenticated-orcid":true,"given":"Mark A.","family":"Arick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Sobhy","family":"Dawood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basant","family":"Gomaa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-7176","authenticated-orcid":true,"given":"Monzur","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry A.","family":"Hanson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Karsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"pone.0340053.ref001","volume-title":"Catfish production","author":"National Agricultural Statistics Service NA","year":"2023"},{"key":"pone.0340053.ref002","first-page":"387","article-title":"Infectious diseases.","volume-title":"Bio-logy and culture of channel catfish","author":"JP Hawke","year":"2004"},{"key":"pone.0340053.ref003","volume-title":"Part I: Reference of Fingerling Catfish Health and Production Practices in the United States","author":"USDA","year":"2003"},{"key":"pone.0340053.ref004","doi-asserted-by":"crossref","unstructured":"Wise AL, LaFrentz BR. A review of bacterial co-infections in farmed catfish: components, diagnostics, and treatment directions. 2021;11(11).","DOI":"10.3390\/ani11113240"},{"issue":"8","key":"pone.0340053.ref005","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/jfd.12431","article-title":"Comparison of Edwardsiella ictaluri isolates from different hosts and geographic origins","volume":"39","author":"MJ Griffin","year":"2016","journal-title":"J Fish Dis"},{"issue":"1","key":"pone.0340053.ref006","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/aah.10207","article-title":"Flavobacterium covae is the predominant species of columnaris-causing bacteria impacting the Channel Catfish industry in the southeastern United States","volume":"36","author":"BR LaFrentz","year":"2024","journal-title":"J Aquat Anim Health"},{"issue":"9","key":"pone.0340053.ref007","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1111\/jfd.13453","article-title":"Virulence and live vaccine potential of 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