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Title: Protein A suppresses immune responses during Staphylococcus aureus 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 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.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Univ. of Chicago, IL (United States). Dept. of Microbiology; Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1201740
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
mBio (Online)
Additional Journal Information:
Journal Name: mBio (Online); Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2150-7511
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Kim, Hwan Keun, Falugi, Fabiana, Thomer, Lena, Missiakas, Dominique M., and Schneewind, Olaf. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs. United States: N. p., 2015. Web. doi:10.1128/mBio.02369-14.
Kim, Hwan Keun, Falugi, Fabiana, Thomer, Lena, Missiakas, Dominique M., & Schneewind, Olaf. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs. United States. https://doi.org/10.1128/mBio.02369-14
Kim, Hwan Keun, Falugi, Fabiana, Thomer, Lena, Missiakas, Dominique M., and Schneewind, Olaf. Tue . "Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs". United States. https://doi.org/10.1128/mBio.02369-14. https://www.osti.gov/servlets/purl/1201740.
@article{osti_1201740,
title = {Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs},
author = {Kim, Hwan Keun and Falugi, Fabiana and Thomer, Lena and Missiakas, Dominique M. and Schneewind, Olaf},
abstractNote = {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.},
doi = {10.1128/mBio.02369-14},
journal = {mBio (Online)},
number = 1,
volume = 6,
place = {United States},
year = {2015},
month = {1}
}

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