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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-FARM2FORK-01-06 Call. The work of P.M.M. and M.J.d.M. (CITA) was also supported by the Aragon Government (Grupo de Investigacion A21_23R).

Analysis of institutional authors

De Miguel, Maria JesusAuthorMunoz, Pilar MAuthor

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November 14, 2024
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Disruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccine

Publicated to:International Journal Of Molecular Sciences. 25 (20): 11230- - 2024-10-01 25(20), DOI: 10.3390/ijms252011230

Authors: Elizalde-Bielsa, Aitor; Lazaro-Anton, Leticia; de Miguel, Maria Jesus; Munoz, Pilar M; Conde-Alvarez, Raquel; Zuniga-Ripa, Amaia

Affiliations

Ctr Invest & Tecnol Agroalimentaria Aragon CITA, Dept Anim Sci, Zaragoza 50059, Spain - Author
Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA - Author
Univ Navarra, Dept Microbiol & Parasitol, Inst Invest Sanitaria Navarra IdiSNA, Pamplona 31008, Spain - Author
Univ Zaragoza, Inst Agroalimentario Aragon IA2, CITA, Zaragoza 50009, Spain - Author

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 Delta fba Delta 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 Delta fba Delta tal provided comparable protection to the Rev1 reference vaccine while inducing fewer adverse reproductive events in pregnant animals. Altogether, these results postulate the Rev1 Delta fba Delta tal mutant as a reproductively safer Rev1-derived vaccine candidate to be studied in the natural host.

Keywords

<italic>brucella</italic>AbortionAbortoAbortusAldehído liasaBrucellaCell-lineComplicaciones del embarazoEmbriones animalesErythritolEstablishmentFbaFull virulenceLesionsLocalizationPathogenesisPlacentPlacentaPlacental pathologyPregnancy safetyReplicatioRev1SuisTalTrophoblastsVaccineVacuna

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal International Journal Of Molecular Sciences due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 68/231, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-12:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 12.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/10532/7356

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.