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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. doi: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. doi: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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Works referenced in this record:

Staphylococcus aureus Infections
journal, August 1998


The Impact of Antimicrobial‐Resistant, Health Care–Associated Infections on Mortality in the United States
journal, October 2008

  • Klevens, R. Monina; Edwards, Jonathan R.; Gaynes, R. P.
  • Clinical Infectious Diseases, Vol. 47, Issue 7
  • DOI: 10.1086/591698

Development of a vaccine against Staphylococcus aureus
journal, November 2011


Use of a Staphylococcus aureus Conjugate Vaccine in Patients Receiving Hemodialysis
journal, February 2002

  • Shinefield, Henry; Black, Steven; Fattom, Ali
  • New England Journal of Medicine, Vol. 346, Issue 7
  • DOI: 10.1056/NEJMoa011297

Passage of Heme-Iron Across the Envelope of Staphylococcus aureus
journal, February 2003


Recurrent infections and immune evasion strategies of Staphylococcus aureus
journal, February 2012

  • Kim, Hwan Keun; Thammavongsa, Vilasack; Schneewind, Olaf
  • Current Opinion in Microbiology, Vol. 15, Issue 1
  • DOI: 10.1016/j.mib.2011.10.012

Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
journal, August 2010

  • Kim, Hwan Keun; Cheng, Alice G.; Kim, Hye-Young
  • The Journal of Experimental Medicine, Vol. 207, Issue 9
  • DOI: 10.1084/jem.20092514

Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus
journal, March 2006


Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif
journal, October 1999

  • Ton-That, H.; Liu, G.; Mazmanian, S. K.
  • Proceedings of the National Academy of Sciences, Vol. 96, Issue 22
  • DOI: 10.1073/pnas.96.22.12424

An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis
journal, February 2002

  • Mazmanian, S. K.; Ton-That, H.; Su, K.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 4
  • DOI: 10.1073/pnas.032523999

Identifying protective antigens of Staphylococcus aureus , a pathogen that suppresses host immune responses
journal, July 2011

  • Kim, Hwan Keun; Kim, Hye‐Young; Schneewind, Olaf
  • The FASEB Journal, Vol. 25, Issue 10
  • DOI: 10.1096/fj.11-187963

Studies on transformation of Escherichia coli with plasmids
journal, June 1983