Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner

Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner

Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ vir...

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Main Authors: Kasper, Katherine J., Zeppa, Joseph J., Wakabayashi, Adrienne T., Xu, Stacey X., Mazzuca, Delfina M., Welch, Ian, Baroja, Miren L., Kotb, Malak, Cairns, Ewa, Cleary, P. Patrick, Haeryfar, S. M. Mansour, McCormick, John K.
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038607/
id pubmed-4038607
recordtype oai_dc
spelling pubmed-40386072014-06-05 Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner Kasper, Katherine J. Zeppa, Joseph J. Wakabayashi, Adrienne T. Xu, Stacey X. Mazzuca, Delfina M. Welch, Ian Baroja, Miren L. Kotb, Malak Cairns, Ewa Cleary, P. Patrick Haeryfar, S. M. Mansour McCormick, John K. Research Article Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC –II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms. Public Library of Science 2014-05-29 /pmc/articles/PMC4038607/ /pubmed/24875883 http://dx.doi.org/10.1371/journal.ppat.1004155 Text en © 2014 Kasper et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kasper, Katherine J.
Zeppa, Joseph J.
Wakabayashi, Adrienne T.
Xu, Stacey X.
Mazzuca, Delfina M.
Welch, Ian
Baroja, Miren L.
Kotb, Malak
Cairns, Ewa
Cleary, P. Patrick
Haeryfar, S. M. Mansour
McCormick, John K.
spellingShingle Kasper, Katherine J.
Zeppa, Joseph J.
Wakabayashi, Adrienne T.
Xu, Stacey X.
Mazzuca, Delfina M.
Welch, Ian
Baroja, Miren L.
Kotb, Malak
Cairns, Ewa
Cleary, P. Patrick
Haeryfar, S. M. Mansour
McCormick, John K.
Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner
author_facet Kasper, Katherine J.
Zeppa, Joseph J.
Wakabayashi, Adrienne T.
Xu, Stacey X.
Mazzuca, Delfina M.
Welch, Ian
Baroja, Miren L.
Kotb, Malak
Cairns, Ewa
Cleary, P. Patrick
Haeryfar, S. M. Mansour
McCormick, John K.
author_sort Kasper, Katherine J.
title Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner
title_short Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner
title_full Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner
title_fullStr Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner
title_full_unstemmed Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner
title_sort bacterial superantigens promote acute nasopharyngeal infection by streptococcus pyogenes in a human mhc class ii-dependent manner
description Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC –II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038607/
_version_ 1612094589273899008

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