Disruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccine
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Date
2024
Authors
Elizalde Bielsa, AitorLázaro-Antón, Leticia
Miguel López, María Jesús de
Muñoz Álvaro, Pilar María
Conde-Alvarez, Raquel
Zúñiga Ripa, Amaia
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Abstract
Brucellosis 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.
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Bibliographic citation
Elizalde-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
AGROVOC subjects
BrucellaVacuna
Aldehído liasa
Embriones animales
Complicaciones del embarazo
Aborto
Placenta
Other field subjects
AbortoAldehído Liasa
Brucella
Complicaciones Del Embarazo
Embriones Animales
Placenta
Vacuna
Sponsorship
This 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).