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In these natural hosts, brucellae display a tropism towards the reproductive organs, such as the placenta, replicating in high numbers and leading to placentitis and abortion, an ability also exerted by the B. melitensis live-attenuated Rev1 strain, the only vaccine available for ovine brucellosis. It is broadly accepted that this tropism is mediated, at least in part, by the presence of certain preferred nutrients in the placenta, particularly erythritol, a polyol that is ultimately incorporated into the Brucella central carbon metabolism via two reactions dependent on transaldolase (Tal) or fructose-bisphosphate aldolase (Fba). In the light of these remarks, we propose that blocking the incorporation of erythritol into the central carbon metabolism of Rev1 by deleting the genes encoding Tal and Fba may impair the ability of the vaccine to proliferate massively in the placenta. Therefore, a Rev1\u0394fba\u0394tal double mutant was generated and confirmed to be unable to use erythritol. This mutant exhibited a reduced intracellular fitness both in BeWo trophoblasts and THP-1 macrophages. In the murine model, Rev1\u0394fba\u0394tal provided comparable protection to the Rev1 reference vaccine while inducing fewer adverse reproductive events in pregnant animals. Altogether, these results postulate the Rev1\u0394fba\u0394tal mutant as a reproductively safer Rev1-derived vaccine candidate to be studied in the natural host.<\/jats:p>","DOI":"10.3390\/ijms252011230","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T03:57:09Z","timestamp":1729483029000},"page":"11230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccine"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3836-9650","authenticated-orcid":false,"given":"Aitor","family":"Elizalde-Bielsa","sequence":"first","affiliation":[{"name":"Department of Microbiology and Parasitology, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7720-5627","authenticated-orcid":false,"given":"Leticia","family":"L\u00e1zaro-Ant\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), University of Navarra, 31008 Pamplona, Spain"},{"name":"Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jes\u00fas","family":"de Miguel","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Centro de Investigaci\u00f3n y Tecnolog\u00eda Agroalimentaria de Arag\u00f3n (CITA), 50059 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n\u2014IA2, CITA-Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar M.","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Centro de Investigaci\u00f3n y Tecnolog\u00eda Agroalimentaria de Arag\u00f3n (CITA), 50059 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n\u2014IA2, CITA-Universidad de Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0046-3577","authenticated-orcid":false,"given":"Raquel","family":"Conde-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-8994","authenticated-orcid":false,"given":"Amaia","family":"Z\u00fa\u00f1iga-Ripa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Occhialini, A., Hofreuter, D., Ufermann, C., Al Dahouk, S., and K\u00f6hler, S. 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