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Brucella melitensis wzm/wzt system: changes in the bacterial envelope lead to improved rev1Δwzm vaccine properties

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dc.contributor.authorMena Bueno, Sara
dc.contributor.authorPoveda Urkixo, Irati
dc.contributor.authorIrazoki, Oihane
dc.contributor.authorPalacios Chaves, Leyre
dc.contributor.authorCava, Felipe
dc.contributor.authorZabalza Baranguá, Ana
dc.contributor.authorGrilló Dolset, María Jesús
dc.contributor.departmentAgronomía, Biotecnología y Alimentaciónes_ES
dc.contributor.departmentAgronomia, Bioteknologia eta Elikaduraeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2023-02-23T07:16:50Z
dc.date.available2023-02-23T07:16:50Z
dc.date.issued2022
dc.date.updated2023-02-23T06:57:39Z
dc.description.abstractThe lipopolysaccharide (LPS) O-polysaccharide (O-PS) is the main virulence factor in Brucella. After synthesis in the cytoplasmic membrane, O-PS is exported to the periplasm by the Wzm/Wzt system, where it is assembled into a LPS. This translocation also engages a bactoprenol carrier required for further biosynthesis pathways, such as cell wall biogenesis. Targeting O-PS export by blockage holds great potential for vaccine development, but little is known about the biological implications of each Wzm/Wzt moiety. To improve this knowledge and to elucidate its potential application as a vaccine, we constructed and studied wzm/wzt single- and double-deletion mutants, using the attenuated strain Brucella melitensis Rev1 as the parental strain. This allowed us to describe the composition of Brucella peptidoglycan for the first time. We observed that these mutants lack external O-PS yet trigger changes in genetic transcription and in phenotypic properties associated with the outer membrane and cell wall. The three mutants are highly attenuated; unexpectedly, Rev1Δwzm also excels as an immunogenic and effective vaccine against B. melitensis and Brucella ovis in mice, revealing that low persistence is not at odds with efficacy. Rev1Δwzm is attenuated in BeWo trophoblasts, does not infect mouse placentas, and is safe in pregnant ewes. Overall, these attributes and the minimal serological interference induced in sheep make Rev1Δwzm a highly promising vaccine candidate.en
dc.description.sponsorshipThis work was funded by Agencia Estatal de Investigación of the Ministerio de Ciencia, Innovación y Universidades (AGL2014-58795-C4-2-R and RTI2018-098658-B-C21), Gobierno de Navarra (PT040-2018 and PT007-2019) projects. SM-B contracts were granted by the FEDER 2016–2018 program of Garantía Juvenil and by an UPNA pre-doctoral fellowship 2018–2022. IP-U Doctorados Industriales contract was cofounded by Gobierno de Navarra and CSIC. Research in the FC lab was supported by The Swedish Research Council (VR), The Knut and Alice Wallenberg Foundation (KAW), The Laboratory of Molecular Infection Medicine Sweden (MIMS), and The Kempe Foundation.en
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dc.format.mimetypeapplication/zipen
dc.identifier.citationMena-Bueno, S., Poveda-Urkixo, I., Irazoki, O., Palacios, L., Cava, F., Zabalza-Baranguá, A., & Grilló, M. J. (2022). Brucella melitensis wzm/wzt system: Changes in the bacterial envelope lead to improved rev1δwzm vaccine properties. Frontiers in Microbiology, 13. https://www.frontiersin.org/articles/10.3389/fmicb.2022.908495en
dc.identifier.doi10.3389/fmicb.2022.908495
dc.identifier.issn1664-302X
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/44786
dc.language.isoengen
dc.publisherFrontiers Mediaen
dc.relation.ispartofFrontiers in Microbiology 13(908495) 1-20en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//AGL2014-58795-C4-2-R/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098658-B-C21/ES/en
dc.relation.publisherversionhttps://doi.org/10.3389/fmicb.2022.908495
dc.rights© 2022 Mena-Bueno, Poveda-Urkixo, Irazoki, Palacios, Cava, Zabalza- Baranguá and Grilló. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBrucella envelopeen
dc.subjectLipopolysaccharideen
dc.subjectPregnant miceen
dc.subjectPregnant sheepen
dc.subjectRev1Δwzm vaccineen
dc.subjectWzm/Wzt systemen
dc.titleBrucella melitensis wzm/wzt system: changes in the bacterial envelope lead to improved rev1Δwzm vaccine propertiesen
dc.typeinfo:eu-repo/semantics/article
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
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relation.isAuthorOfPublication618f91fb-38b4-4e6c-b43b-12075328c848
relation.isAuthorOfPublication.latestForDiscovery618f91fb-38b4-4e6c-b43b-12075328c848

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