Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates
Live attenuated vaccines (LAVs) whose virulence would be controlled at the tissue level could be a crucial tool to effectively fight intracellular bacterial pathogens, because they would optimize the induction of protective immune memory while avoiding the long-term persistence of vaccine strains in...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/111960 |
| Acceso en línea: | https://hdl.handle.net/10171/111960 |
| Access Level: | acceso abierto |
| Palabra clave: | Brucella melitensis Vaccine |
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Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidatesBarbieux, E. (Emeline)|||/items/15351303-10e2-44da-a97c-9db0ce3eaee4Potemberg, G. (Georges)|||/items/11bcd0f2-2f71-45f6-a760-6bf7a23d2e82Stubbe, F.X. (François Xavier)|||/items/df4d1491-ccbe-4fb1-b8b8-ec8ac7119dafFraikin, A. (Audrey)|||/items/6d891061-f10d-4d40-bb64-464f3889bfddPoncin, K. (Katy)|||/items/75d391cc-4599-40fc-abc2-8e830022d462Reboul, A. (Angeline)|||/items/d0466b45-f348-46ce-baf1-43867c063a9cRouma, T. (Thomas)|||/items/feb9de46-95cd-44be-b7d2-06eff99d1adcZuñiga-Ripa, A. (Amaia)|||/items/9aa6da2e-e507-4319-a12c-092436f70febBolle, X. (Xavier) de|||/items/4e775989-350e-41ce-bbfc-4f4a0eee72acMuraille, E. (Eric)|||/items/30c8cc4c-1b4b-45e8-acd2-cb46398e98b2Brucella melitensisVaccineLive attenuated vaccines (LAVs) whose virulence would be controlled at the tissue level could be a crucial tool to effectively fight intracellular bacterial pathogens, because they would optimize the induction of protective immune memory while avoiding the long-term persistence of vaccine strains in the host. Rational development of these new LAVs implies developing an exhaustive map of the bacterial virulence genes according to the host organs implicated. We report here the use of transposon sequencing to compare the bacterial genes involved in the multiplication of Brucella melitensis, a major causative agent of brucellosis, in the lungs and spleens of C57BL/6 infected mice. We found 257 and 135 genes predicted to be essential for B. melitensis multiplication in the spleen and lung, respectively, with 87 genes common to both organs. We selected genes whose deletion is predicted to produce moderate or severe attenuation in the spleen, the main known reservoir of Brucella, and compared deletion mutants for these genes for their ability to protect mice against challenge with a virulent strain of B. melitensis. The protective efficacy of a deletion mutant for the plsC gene, implicated in phospholipid biosynthesis, is similar to that of the reference Rev.1 vaccine but with a shorter persistence in the spleen. Our results demonstrate that B. melitensis faces different selective pressures depending on the organ and underscore the effectiveness of functional genome mapping for the design of new safer LAV candidates.PLOSDadun. Depósito Académico Digital Universidad de Navarra20242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/111960reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1119602026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| title |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| spellingShingle |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates Barbieux, E. (Emeline)|||/items/15351303-10e2-44da-a97c-9db0ce3eaee4 Brucella melitensis Vaccine |
| title_short |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| title_full |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| title_fullStr |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| title_full_unstemmed |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| title_sort |
Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates |
| dc.creator.none.fl_str_mv |
Barbieux, E. (Emeline)|||/items/15351303-10e2-44da-a97c-9db0ce3eaee4 Potemberg, G. (Georges)|||/items/11bcd0f2-2f71-45f6-a760-6bf7a23d2e82 Stubbe, F.X. (François Xavier)|||/items/df4d1491-ccbe-4fb1-b8b8-ec8ac7119daf Fraikin, A. (Audrey)|||/items/6d891061-f10d-4d40-bb64-464f3889bfdd Poncin, K. (Katy)|||/items/75d391cc-4599-40fc-abc2-8e830022d462 Reboul, A. (Angeline)|||/items/d0466b45-f348-46ce-baf1-43867c063a9c Rouma, T. (Thomas)|||/items/feb9de46-95cd-44be-b7d2-06eff99d1adc Zuñiga-Ripa, A. (Amaia)|||/items/9aa6da2e-e507-4319-a12c-092436f70feb Bolle, X. (Xavier) de|||/items/4e775989-350e-41ce-bbfc-4f4a0eee72ac Muraille, E. (Eric)|||/items/30c8cc4c-1b4b-45e8-acd2-cb46398e98b2 |
| author |
Barbieux, E. (Emeline)|||/items/15351303-10e2-44da-a97c-9db0ce3eaee4 |
| author_facet |
Barbieux, E. (Emeline)|||/items/15351303-10e2-44da-a97c-9db0ce3eaee4 Potemberg, G. (Georges)|||/items/11bcd0f2-2f71-45f6-a760-6bf7a23d2e82 Stubbe, F.X. (François Xavier)|||/items/df4d1491-ccbe-4fb1-b8b8-ec8ac7119daf Fraikin, A. (Audrey)|||/items/6d891061-f10d-4d40-bb64-464f3889bfdd Poncin, K. (Katy)|||/items/75d391cc-4599-40fc-abc2-8e830022d462 Reboul, A. (Angeline)|||/items/d0466b45-f348-46ce-baf1-43867c063a9c Rouma, T. (Thomas)|||/items/feb9de46-95cd-44be-b7d2-06eff99d1adc Zuñiga-Ripa, A. (Amaia)|||/items/9aa6da2e-e507-4319-a12c-092436f70feb Bolle, X. (Xavier) de|||/items/4e775989-350e-41ce-bbfc-4f4a0eee72ac Muraille, E. (Eric)|||/items/30c8cc4c-1b4b-45e8-acd2-cb46398e98b2 |
| author_role |
author |
| author2 |
Potemberg, G. (Georges)|||/items/11bcd0f2-2f71-45f6-a760-6bf7a23d2e82 Stubbe, F.X. (François Xavier)|||/items/df4d1491-ccbe-4fb1-b8b8-ec8ac7119daf Fraikin, A. (Audrey)|||/items/6d891061-f10d-4d40-bb64-464f3889bfdd Poncin, K. (Katy)|||/items/75d391cc-4599-40fc-abc2-8e830022d462 Reboul, A. (Angeline)|||/items/d0466b45-f348-46ce-baf1-43867c063a9c Rouma, T. (Thomas)|||/items/feb9de46-95cd-44be-b7d2-06eff99d1adc Zuñiga-Ripa, A. (Amaia)|||/items/9aa6da2e-e507-4319-a12c-092436f70feb Bolle, X. (Xavier) de|||/items/4e775989-350e-41ce-bbfc-4f4a0eee72ac Muraille, E. (Eric)|||/items/30c8cc4c-1b4b-45e8-acd2-cb46398e98b2 |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Brucella melitensis Vaccine |
| topic |
Brucella melitensis Vaccine |
| description |
Live attenuated vaccines (LAVs) whose virulence would be controlled at the tissue level could be a crucial tool to effectively fight intracellular bacterial pathogens, because they would optimize the induction of protective immune memory while avoiding the long-term persistence of vaccine strains in the host. Rational development of these new LAVs implies developing an exhaustive map of the bacterial virulence genes according to the host organs implicated. We report here the use of transposon sequencing to compare the bacterial genes involved in the multiplication of Brucella melitensis, a major causative agent of brucellosis, in the lungs and spleens of C57BL/6 infected mice. We found 257 and 135 genes predicted to be essential for B. melitensis multiplication in the spleen and lung, respectively, with 87 genes common to both organs. We selected genes whose deletion is predicted to produce moderate or severe attenuation in the spleen, the main known reservoir of Brucella, and compared deletion mutants for these genes for their ability to protect mice against challenge with a virulent strain of B. melitensis. The protective efficacy of a deletion mutant for the plsC gene, implicated in phospholipid biosynthesis, is similar to that of the reference Rev.1 vaccine but with a shorter persistence in the spleen. Our results demonstrate that B. melitensis faces different selective pressures depending on the organ and underscore the effectiveness of functional genome mapping for the design of new safer LAV candidates. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-01-01 2024 2024-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/111960 |
| url |
https://hdl.handle.net/10171/111960 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
PLOS |
| publisher.none.fl_str_mv |
PLOS |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
| reponame_str |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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| repository.mail.fl_str_mv |
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1869406009130221568 |
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15,811543 |