Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs

ABSTRACT Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant fo...

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Autores principales:	Hwan Keun Kim, Fabiana Falugi, Lena Thomer, Dominique M. Missiakas, Olaf Schneewind
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4d1b89301df14297a4a49ee2eb45a3bb
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spelling	oai:doaj.org-article:4d1b89301df14297a4a49ee2eb45a3bb2021-11-15T15:41:19ZProtein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs10.1128/mBio.02369-142150-7511https://doaj.org/article/4d1b89301df14297a4a49ee2eb45a3bb2015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02369-14https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. IMPORTANCE Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines.Hwan Keun KimFabiana FalugiLena ThomerDominique M. MissiakasOlaf SchneewindAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Hwan Keun Kim Fabiana Falugi Lena Thomer Dominique M. Missiakas Olaf Schneewind Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs
description	ABSTRACT Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. IMPORTANCE Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines.
format	article
author	Hwan Keun Kim Fabiana Falugi Lena Thomer Dominique M. Missiakas Olaf Schneewind
author_facet	Hwan Keun Kim Fabiana Falugi Lena Thomer Dominique M. Missiakas Olaf Schneewind
author_sort	Hwan Keun Kim
title	Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs
title_short	Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs
title_full	Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs
title_fullStr	Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs
title_full_unstemmed	Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs
title_sort	protein a suppresses immune responses during <named-content content-type="genus-species">staphylococcus aureus</named-content> bloodstream infection in guinea pigs
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/4d1b89301df14297a4a49ee2eb45a3bb
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Protein A Suppresses Immune Responses during <named-content content-type="genus-species">Staphylococcus aureus</named-content> Bloodstream Infection in Guinea Pigs

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