Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains

ABSTRACT Salmonella enterica serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized in vivo. We used an in vivo expression technology (IVET) strategy to identify four fimbrial...

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Autores principales:	Paweł Łaniewski, Chang-Ho Baek, Kenneth L. Roland, Roy Curtiss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Agf Saf Stc Sti fimbriae in vivo expression Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ade21a3b121a49e490e0310ad56b91cb
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spelling	oai:doaj.org-article:ade21a3b121a49e490e0310ad56b91cb2021-11-15T15:51:43ZAnalysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains10.1128/mBio.01189-172150-7511https://doaj.org/article/ade21a3b121a49e490e0310ad56b91cb2017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01189-17https://doaj.org/toc/2150-7511ABSTRACT Salmonella enterica serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized in vivo. We used an in vivo expression technology (IVET) strategy to identify four fimbrial operons, agf, saf, sti, and stc that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 × 105 CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 × 109 CFU of wild-type S. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a Salmonella vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, χ9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the Streptococcus pneumoniae antigen PspA. Strains that constitutively expressed saf or stc elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying saf or stc deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent S. pneumoniae. Our results indicate that these fimbriae play important roles, as yet not understood, in Salmonella virulence and immunogenicity. IMPORTANCE Salmonella enterica is the leading cause of bacterial food-borne infection in the United States. S. Typhimurium is capable of producing up to 13 distinct surface structures called fimbriae that presumably mediate its adherence to surfaces. The roles of most of these fimbriae in disease are unknown. Identifying fimbriae produced during infection will provide important insights into how these bacterial structures contribute to disease and potentially induce protective immunity to Salmonella infection. We identified four fimbriae that are produced during infection. Deletion of all four of these fimbriae results in a significant reduction in virulence. We explored ways in which the expression of these fimbriae may be exploited for use in recombinant Salmonella vaccine strains and found that production of Saf and Stc fimbriae are important for generating a strong immune response against a vectored antigen. This work provides new insight into the role of fimbriae in disease and their potential for improving the efficacy of Salmonella-based vaccines.Paweł ŁaniewskiChang-Ho BaekKenneth L. RolandRoy CurtissAmerican Society for MicrobiologyarticleAgfSafStcStifimbriaein vivo expressionMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Agf Saf Stc Sti fimbriae in vivo expression Microbiology QR1-502
spellingShingle	Agf Saf Stc Sti fimbriae in vivo expression Microbiology QR1-502 Paweł Łaniewski Chang-Ho Baek Kenneth L. Roland Roy Curtiss Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains
description	ABSTRACT Salmonella enterica serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized in vivo. We used an in vivo expression technology (IVET) strategy to identify four fimbrial operons, agf, saf, sti, and stc that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 × 105 CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 × 109 CFU of wild-type S. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a Salmonella vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, χ9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the Streptococcus pneumoniae antigen PspA. Strains that constitutively expressed saf or stc elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying saf or stc deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent S. pneumoniae. Our results indicate that these fimbriae play important roles, as yet not understood, in Salmonella virulence and immunogenicity. IMPORTANCE Salmonella enterica is the leading cause of bacterial food-borne infection in the United States. S. Typhimurium is capable of producing up to 13 distinct surface structures called fimbriae that presumably mediate its adherence to surfaces. The roles of most of these fimbriae in disease are unknown. Identifying fimbriae produced during infection will provide important insights into how these bacterial structures contribute to disease and potentially induce protective immunity to Salmonella infection. We identified four fimbriae that are produced during infection. Deletion of all four of these fimbriae results in a significant reduction in virulence. We explored ways in which the expression of these fimbriae may be exploited for use in recombinant Salmonella vaccine strains and found that production of Saf and Stc fimbriae are important for generating a strong immune response against a vectored antigen. This work provides new insight into the role of fimbriae in disease and their potential for improving the efficacy of Salmonella-based vaccines.
format	article
author	Paweł Łaniewski Chang-Ho Baek Kenneth L. Roland Roy Curtiss
author_facet	Paweł Łaniewski Chang-Ho Baek Kenneth L. Roland Roy Curtiss
author_sort	Paweł Łaniewski
title	Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains
title_short	Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains
title_full	Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains
title_fullStr	Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains
title_full_unstemmed	Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains
title_sort	analysis of spleen-induced fimbria production in recombinant attenuated <italic toggle="yes">salmonella enterica</italic> serovar typhimurium vaccine strains
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/ade21a3b121a49e490e0310ad56b91cb
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Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Vaccine Strains

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