{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:07:57Z","timestamp":1784092077710,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"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. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Salmonella enterica serovar Enteritidis<\/jats:italic>\n (\n S<\/jats:italic>\n . Enteritidis) is a leading global cause of foodborne illnesses. The emergence of multidrug-resistant strains has exacerbated clinical treatment challenges and public health threats. The tricarboxylic acid (TCA) cycle is central to bacterial carbon metabolism, with key enzyme-encoding genes linked to environmental adaptation and pathogenicity. However, the biological role of \u0394\n gltA<\/jats:italic>\n , which encodes citrate synthase, the rate-limiting enzyme initiating the TCA cycle, in\n S<\/jats:italic>\n . Enteritidis, and its potential as an attenuated vaccine target remain poorly understood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We constructed a\n gltA<\/jats:italic>\n deletion mutant (\u0394\n gltA<\/jats:italic>\n ) and its complemented strain (\u0394\n gltA<\/jats:italic>\n +\n gltA<\/jats:italic>\n ) from\n S<\/jats:italic>\n . Enteritidis C50336of using \u03bb-Red homologous recombination. We systematically characterized the effects of \u0394\n gltA<\/jats:italic>\n deletion on bacterial growth, antimicrobial susceptibility, and stress tolerance. Transcriptomics and qRT-PCR were employed to investigate virulence regulation mechanisms, while mouse models were used to evaluate attenuation and immunoprotective efficacy.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n \u0394\n gltA<\/jats:italic>\n deletion did not alter growth in nutrient-rich LB or nutrient-poor M9 media, but significantly impaired motility and biofilm formation by inhibiting curli fimbriae and cellulose synthesis, and increased susceptibility to 15 antimicrobial agents. The \u0394\n gltA<\/jats:italic>\n mutant also showed reduced tolerance to acidic, alkaline, oxidative, thermal, and osmotic stresses. Notably, intraperitoneal infection revealed &gt;10\n 6<\/jats:sup>\n -fold attenuation in Kunming mice (wild-type LD\n 50<\/jats:sub>\n = 3.16 \u00d7 10\u00b3 CFU; no mortality at 1 \u00d7 10\n 9<\/jats:sup>\n CFU \u0394\n gltA<\/jats:italic>\n ), with decreased organ bacterial loads and global downregulation of 24 key virulence genes. A single oral immunization with \u0394\n gltA<\/jats:italic>\n elicited robust humoral and cellular immunity, conferring promising protection against lethal wild-type challenge.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Deletion of \u0394\n gltA<\/jats:italic>\n is associated with altered metabolic homeostasis, impaired environmental adaptability and attenuated pathogenicity in\n S<\/jats:italic>\n . Enteritidis. The \u0394\n gltA<\/jats:italic>\n mutant conferred effective protective immunity in the mouse model used here, serving as a promising candidate strain and molecular target for further development of live attenuated\n S<\/jats:italic>\n . Enteritidis vaccines.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1869123","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:42:18Z","timestamp":1784090538000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of gltA attenuates virulence and confers immune protection against Salmonella Enteritidis"],"prefix":"10.3389","volume":"17","author":[{"given":"Siping","family":"Zhu","sequence":"first","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]},{"name":"Public Health Department, Wuhan 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowang","family":"Chen","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ren","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihuan","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiumei","family":"Shi","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science & Technology","place":["Qinhuangdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12879-025-10478-5","article-title":"Combatting salmonella: a focus on antimicrobial resistance and the need for effective 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