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IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/I...

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Autores principales: Okumura, Cheryl Y. M., Anderson, Ericka L., Döhrmann, Simon, Tran, Dan N., Olson, Joshua, von Pawel-Rammingen, Ulrich, Nizet, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735186/
https://www.ncbi.nlm.nih.gov/pubmed/23900173
http://dx.doi.org/10.1128/mBio.00499-13
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author Okumura, Cheryl Y. M.
Anderson, Ericka L.
Döhrmann, Simon
Tran, Dan N.
Olson, Joshua
von Pawel-Rammingen, Ulrich
Nizet, Victor
author_facet Okumura, Cheryl Y. M.
Anderson, Ericka L.
Döhrmann, Simon
Tran, Dan N.
Olson, Joshua
von Pawel-Rammingen, Ulrich
Nizet, Victor
author_sort Okumura, Cheryl Y. M.
collection PubMed
description The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds.
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spelling pubmed-37351862013-08-08 IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus Okumura, Cheryl Y. M. Anderson, Ericka L. Döhrmann, Simon Tran, Dan N. Olson, Joshua von Pawel-Rammingen, Ulrich Nizet, Victor mBio Research Article The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds. American Society of Microbiology 2013-07-30 /pmc/articles/PMC3735186/ /pubmed/23900173 http://dx.doi.org/10.1128/mBio.00499-13 Text en Copyright © 2013 Okumura et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Okumura, Cheryl Y. M.
Anderson, Ericka L.
Döhrmann, Simon
Tran, Dan N.
Olson, Joshua
von Pawel-Rammingen, Ulrich
Nizet, Victor
IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus
title IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus
title_full IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus
title_fullStr IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus
title_full_unstemmed IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus
title_short IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus
title_sort igg protease mac/ides is not essential for phagocyte resistance or mouse virulence of m1t1 group a streptococcus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735186/
https://www.ncbi.nlm.nih.gov/pubmed/23900173
http://dx.doi.org/10.1128/mBio.00499-13
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