{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:53:44Z","timestamp":1785405224720,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016692","name":"Key Research and Development Program of Ningxia Hui Autonomous Region","doi-asserted-by":"crossref","award":["2024BEG02029"],"award-info":[{"award-number":["2024BEG02029"]}],"id":[{"id":"10.13039\/100016692","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32573464"],"award-info":[{"award-number":["32573464"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32573464"],"award-info":[{"award-number":["32573464"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Innovation Program of Chinese Academy of Agricultural Sciences","award":["CAASASTIP-2021-LVRI"],"award-info":[{"award-number":["CAASASTIP-2021-LVRI"]}]},{"DOI":"10.13039\/501100012421","name":"The Agricultural Science and Technology Innovation Program","doi-asserted-by":"crossref","award":["CAAS-ZDRW202410"],"award-info":[{"award-number":["CAAS-ZDRW202410"]}],"id":[{"id":"10.13039\/501100012421","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: The intracellular pathogen Brucella requires biotin for survival, yet the role of its de novo synthesis intermediate enzyme, BioA, in virulence remains undefined. This study investigates the contribution of BioA to the pathogenicity of Brucella abortus. Methods: We constructed a \u0394BioA mutant in Brucella abortus 104M via homologous recombination and characterized its phenotype using growth assays, electron microscopy, macrophage infection models, and murine splenic colonization. Virulence gene expression was quantified by RT-qPCR. Results: The \u0394BioA mutant exhibited severe growth auxotrophy in a biotin-deficient medium and displayed damaged outer membrane integrity. Furthermore, intracellular survival in macrophages was reduced by approximately 95% compared to the wild-type strain at 48 h post-infection. Notably, mice infected with the mutant showed a significant decrease in both splenic bacterial loads and spleen weight at 3 weeks, concomitant with a marked downregulation of VirB type IV secretion system (T4SS) genes. Conclusions: This study is the first to identify BioA as a critical nexus linking biotin metabolism to Brucella virulence. We demonstrate that BioA deficiency attenuates pathogenicity by impairing both structural integrity and the transcription of key virulence-related genes (VirB operon), thereby nominating BioA as a novel and promising target for anti-brucellosis interventions.<\/jats:p>","DOI":"10.3390\/pathogens15050473","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:09:33Z","timestamp":1777388973000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Link Between Biotin Metabolism and Brucella Virulence: A Study on BioA"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9453-2543","authenticated-orcid":false,"given":"Donghui","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"},{"name":"State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Quan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jiao","sequence":"additional","affiliation":[{"name":"The Third Research Department, Lanzhou Institute of Biological Products Co., Ltd., Gansu Provincial Vaccine Technology Innovation Center, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-6838","authenticated-orcid":false,"given":"Qiaoying","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9639-6932","authenticated-orcid":false,"given":"Qiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/prot.26642","article-title":"Biotin protein ligase as you like it: Either extraordinarily specific or promiscuous protein biotinylation","volume":"92","author":"Cronan","year":"2024","journal-title":"Proteins"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00018-012-1096-0","article-title":"Structure and function of biotin-dependent carboxylases","volume":"70","author":"Tong","year":"2013","journal-title":"Cell. 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