A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa

Pseudomonas aeruginosa is a common Gram-negative opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The development of a broadly protective vaccine against P. aeruginosa remains a major challenge. Here, we used an attenuated strain of Salmonella enterica serovar T...

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Detalles Bibliográficos
Autores: Aguilera-Herce, Julia, García-Quintanilla, Meritxel, Romero-Flores, Rocío, McConnell, Michael J., Ramos-Morales, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/214410
Acceso en línea:http://hdl.handle.net/10261/214410
Access Level:acceso abierto
Palabra clave:PcrV
Pseudomonas aeruginosa
Salmonella-delivered vaccines
SseJ
type III secretion
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spelling A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosaAguilera-Herce, JuliaGarcía-Quintanilla, MeritxelRomero-Flores, RocíoMcConnell, Michael J.Ramos-Morales, FranciscoPcrVPseudomonas aeruginosaSalmonella-delivered vaccinesSseJtype III secretionPseudomonas aeruginosa is a common Gram-negative opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The development of a broadly protective vaccine against P. aeruginosa remains a major challenge. Here, we used an attenuated strain of Salmonella enterica serovar Typhimurium as a vehicle to express P. aeruginosa antigens. A fusion between the S. enterica type III secretion effector protein SseJ and the P. aeruginosa antigen PcrV expressed under the control of the sseA promoter was translocated by Salmonella into host cells in vitro and elicited the generation of specific antibodies in mice. Mice immunized with attenuated Salmonella expressing this fusion had reduced bacterial loads in the spleens and lungs and lower serum levels of proinflammatory cytokines than control mice after P. aeruginosa infection. Importantly, immunized mice also showed significantly enhanced survival in this model. These results suggest that type III secretion effectors of S. enterica are appropriate carriers in the design of a live vaccine to prevent infections caused by P. aeruginosa.This work was supported by Spanish Ministerio de Economía, Industria y Competitividad and the European Regional Development Fund (grant numbers SAF2013-46229-R and SAF2016-75365-R to F.R.-M.). The funding source was not involved in the research or the preparation of the article. M.J.M. is a founder and scientific advisor for the biotechnology company Vaxdyn, S.L.American Society for MicrobiologyMinisterio de Economía, Industria y Competitividad (España)European CommissionVaxdynConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/214410reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-46229-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75365-Rhttp://dx.doi.org/10.1128/mSphere.00116-19Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2144102026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
title A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
spellingShingle A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
Aguilera-Herce, Julia
PcrV
Pseudomonas aeruginosa
Salmonella-delivered vaccines
SseJ
type III secretion
title_short A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
title_full A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
title_fullStr A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
title_full_unstemmed A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
title_sort A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa
dc.creator.none.fl_str_mv Aguilera-Herce, Julia
García-Quintanilla, Meritxel
Romero-Flores, Rocío
McConnell, Michael J.
Ramos-Morales, Francisco
author Aguilera-Herce, Julia
author_facet Aguilera-Herce, Julia
García-Quintanilla, Meritxel
Romero-Flores, Rocío
McConnell, Michael J.
Ramos-Morales, Francisco
author_role author
author2 García-Quintanilla, Meritxel
Romero-Flores, Rocío
McConnell, Michael J.
Ramos-Morales, Francisco
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía, Industria y Competitividad (España)
European Commission
Vaxdyn
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv PcrV
Pseudomonas aeruginosa
Salmonella-delivered vaccines
SseJ
type III secretion
topic PcrV
Pseudomonas aeruginosa
Salmonella-delivered vaccines
SseJ
type III secretion
description Pseudomonas aeruginosa is a common Gram-negative opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The development of a broadly protective vaccine against P. aeruginosa remains a major challenge. Here, we used an attenuated strain of Salmonella enterica serovar Typhimurium as a vehicle to express P. aeruginosa antigens. A fusion between the S. enterica type III secretion effector protein SseJ and the P. aeruginosa antigen PcrV expressed under the control of the sseA promoter was translocated by Salmonella into host cells in vitro and elicited the generation of specific antibodies in mice. Mice immunized with attenuated Salmonella expressing this fusion had reduced bacterial loads in the spleens and lungs and lower serum levels of proinflammatory cytokines than control mice after P. aeruginosa infection. Importantly, immunized mice also showed significantly enhanced survival in this model. These results suggest that type III secretion effectors of S. enterica are appropriate carriers in the design of a live vaccine to prevent infections caused by P. aeruginosa.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/214410
url http://hdl.handle.net/10261/214410
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-46229-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75365-R
http://dx.doi.org/10.1128/mSphere.00116-19
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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