{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:06:54Z","timestamp":1753870014779,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the potential effects of BvfA in reproductive system damage caused by <jats:italic>Brucella<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Brucella<\/jats:italic> intracellular multiplication ability was determined by a gentamicin protection assay; the LDH method was used to determine the lethal effect of <jats:italic>Brucella<\/jats:italic> on TM4 cells. Afterward, Label\u2010free proteomics and LC\u2010MS\/MS metabolomics assays were combined to reveal differential abundant proteins and metabolites of TM4 cells infected with <jats:italic>bvfA<\/jats:italic>\u2010deletion strains and parental strains. Finally, PRM mass spectrometry and western blot analysis were carried out to confirm differential expression of proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This report demonstrated that <jats:italic>bvfA<\/jats:italic>\u2010deletion strains failed to invade TM4 cells and reconstitution of invasion when a strain with gene <jats:italic>bvfA<\/jats:italic> was reintroduced to the deletion strain in 3 h. The <jats:italic>bvfA<\/jats:italic>\u2010deletion exhibited weakened intracellular multiplication compared with parental strains in TM4 cells in 12 h; however, the death rate of TM4 cells infected with <jats:italic>bvfA<\/jats:italic>\u2010deletion strains was higher than that of TM4 cells infected with parental strains. Combined proteomics and metabolomics analyses revealed that the differential abundant proteins and metabolites in TM4 cells infected with <jats:italic>bvfA<\/jats:italic>\u2010deletion and parental strains mainly involved the mineral absorption\u2010related pathway, NADH:ubiquinone oxidoreductase subunit\u2010related mitochondrial respiratory signaling pathway, and sphingolipid signaling pathway of TM4 cells. These three signaling pathways were involved in expression changes of TRPM6\/7, STEAP1, Gnaq, Trp53, Pbk, Tns2, Akt2, and the NADH:ubiquinone oxidoreductase subunit, as well as content changes of <jats:sc>l<\/jats:sc>\u2010Valine, <jats:sc>l<\/jats:sc>\u2010Isoleucine, <jats:sc>l<\/jats:sc>\u2010Methionine, PC, PE DG, and SM metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These results indicated that BvfA of <jats:italic>Brucella abortus<\/jats:italic> S19 affected the above proteins and metabolites in TM4 cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.202300231","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T09:20:23Z","timestamp":1731057623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomics and Metabolomics Study on the Responses of Sertoli Cells Infected With <i>Brucella<\/i> and Its <i>bvfA\u2010<\/i>Deletion Strains"],"prefix":"10.1002","volume":"19","author":[{"given":"Fang","family":"Jia","sequence":"first","affiliation":[{"name":"Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China Ningxia University  Yinchuan Ningxia China"},{"name":"Inner Mongolia Key Laboratory of Molecular Biology School of Basic Medical Sciences Inner Mongolia Medical University  Hohhot China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangliu","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China Ningxia University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological 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