Disruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccine

dc.bibliographicCitation.stpage11230es_ES
dc.bibliographicCitation.titleInternational Journal Of Molecular Sciencesen
dc.bibliographicCitation.volume25es_ES
dc.contributor.authorElizalde Bielsa, Aitores_ES
dc.contributor.authorLázaro-Antón, Leticiaes_ES
dc.contributor.authorMiguel López, María Jesús dees_ES
dc.contributor.authorMuñoz Álvaro, Pilar Maríaes_ES
dc.contributor.authorConde-Alvarez, Raqueles_ES
dc.contributor.authorZúñiga Ripa, Amaiaes_ES
dc.coverage.spatialCiencia animales_ES
dc.date.accessioned2024-11-21T09:57:01Z
dc.date.available2024-11-21T09:57:01Z
dc.date.issued2024es_ES
dc.date.updated2024-10-24T08:26:19Z
dc.description.abstractBrucellosis is a bacterial zoonosis caused by the genus Brucella, which mainly affects domestic animals. 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?fba?tal 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?fba?tal provided comparable protection to the Rev1 reference vaccine while inducing fewer adverse reproductive events in pregnant animals. Altogether, these results postulate the Rev1?fba?tal mutant as a reproductively safer Rev1-derived vaccine candidate to be studied in the natural host.en
dc.description.otherBrucellaes
dc.description.otherRev1es
dc.description.othervaccinees
dc.description.othererythritoles
dc.description.otherFbaes
dc.description.otherTales
dc.description.othertrophoblastses
dc.description.otherpregnancy safetyes
dc.description.otherabortiones
dc.description.otherplacentaes
dc.description.sponsorshipThis research was carried out in the frame of projects PID2023-146797OB-C31, PID2023- 146797OB-C32, PID2019-107601RB-C31 and PID2019-107601RA-C32 financed by MCIN/AEI/ 10.1303910.13039/501100011033. A.E-B’s work was supported by a postdoctoral contract under the REPRODIVAC project Grant Agreement No. 10106081 through the HORIZON-CL6-2021-FARM2FORK01-06 Call. The work of P.M.M. and M.J.d.M. (CITA) was also supported by the Aragón Government (Grupo de Investigación A21_23R).es_ES
dc.description.statusPublishedes_ES
dc.identifier.citationElizalde-Bielsa, A., Lázaro-Antón, L., de Miguel, M.J., Muñoz, P.M., Conde-Álvarez, R., Zúñiga-Ripa, A. Disruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccine. International Journal of Molecular Sciences, 2024, 25, 20, 11230-NA
dc.identifier.issn14220067
dc.identifier.urihttp://hdl.handle.net/10532/7356
dc.language.isoenes_ES
dc.relation.doihttps://doi.org/10.3390/ijms252011230es_ES
dc.relation.urihttps://doi.org/10.3390/ijms252011230es_ES
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Españaes
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/es
dc.subject.agrovocBrucellaes
dc.subject.agrovocVacunaes
dc.subject.agrovocAldehído liasaes
dc.subject.agrovocEmbriones animaleses
dc.subject.agrovocComplicaciones del embarazoes
dc.subject.agrovocAbortoes
dc.subject.agrovocPlacentaes
dc.subject.otherAborto
dc.subject.otherAldehído Liasa
dc.subject.otherBrucella
dc.subject.otherComplicaciones Del Embarazo
dc.subject.otherEmbriones Animales
dc.subject.otherPlacenta
dc.subject.otherVacuna
dc.titleDisruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccineen
dc.typeJournal Contribution*
dc.type.refereedRefereedes_ES
dc.type.specifiedArticlees_ES

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