A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>

ABSTRACT 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...

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Autores principales:	Julia Aguilera-Herce, Meritxell García-Quintanilla, Rocío Romero-Flores, Michael J. McConnell, Francisco Ramos-Morales
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	PcrV Pseudomonas aeruginosa Salmonella-delivered vaccines SseJ type III secretion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3fce0107b7e245e5af8273bc78aa2172
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spelling	oai:doaj.org-article:3fce0107b7e245e5af8273bc78aa21722021-11-15T15:22:21ZA Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>10.1128/mSphere.00116-192379-5042https://doaj.org/article/3fce0107b7e245e5af8273bc78aa21722019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00116-19https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE The Gram-negative bacterium Pseudomonas aeruginosa is an important opportunistic pathogen that causes infections in cystic fibrosis and hospitalized patients. Therapeutic treatments are limited due to the emergence and spread of new antibiotic-resistant strains. In this context, the development of a vaccine is a priority. Here, we used an attenuated strain of Salmonella enterica serovar Typhimurium as a vehicle to express and deliver the Pseudomonas antigen PcrV. This vaccine induced the generation of specific antibodies in mice and protected them from lethal infections with P. aeruginosa. This is an important step toward the development of an effective vaccine for the prevention of infections caused by P. aeruginosa in humans.Julia Aguilera-HerceMeritxell García-QuintanillaRocío Romero-FloresMichael J. McConnellFrancisco Ramos-MoralesAmerican Society for MicrobiologyarticlePcrVPseudomonas aeruginosaSalmonella-delivered vaccinesSseJtype III secretionMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	PcrV Pseudomonas aeruginosa Salmonella-delivered vaccines SseJ type III secretion Microbiology QR1-502
spellingShingle	PcrV Pseudomonas aeruginosa Salmonella-delivered vaccines SseJ type III secretion Microbiology QR1-502 Julia Aguilera-Herce Meritxell García-Quintanilla Rocío Romero-Flores Michael J. McConnell Francisco Ramos-Morales A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
description	ABSTRACT 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. IMPORTANCE The Gram-negative bacterium Pseudomonas aeruginosa is an important opportunistic pathogen that causes infections in cystic fibrosis and hospitalized patients. Therapeutic treatments are limited due to the emergence and spread of new antibiotic-resistant strains. In this context, the development of a vaccine is a priority. Here, we used an attenuated strain of Salmonella enterica serovar Typhimurium as a vehicle to express and deliver the Pseudomonas antigen PcrV. This vaccine induced the generation of specific antibodies in mice and protected them from lethal infections with P. aeruginosa. This is an important step toward the development of an effective vaccine for the prevention of infections caused by P. aeruginosa in humans.
format	article
author	Julia Aguilera-Herce Meritxell García-Quintanilla Rocío Romero-Flores Michael J. McConnell Francisco Ramos-Morales
author_facet	Julia Aguilera-Herce Meritxell García-Quintanilla Rocío Romero-Flores Michael J. McConnell Francisco Ramos-Morales
author_sort	Julia Aguilera-Herce
title	A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_short	A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_full	A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_fullStr	A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_full_unstemmed	A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_sort	live <italic toggle="yes">salmonella</italic> vaccine delivering pcrv through the type iii secretion system protects against <named-content content-type="genus-species">pseudomonas aeruginosa</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/3fce0107b7e245e5af8273bc78aa2172
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A Live <italic toggle="yes">Salmonella</italic> Vaccine Delivering PcrV through the Type III Secretion System Protects against <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>

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