IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>

ABSTRACT 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cheryl Y. M. Okumura, Ericka L. Anderson, Simon Döhrmann, Dan N. Tran, Joshua Olson, Ulrich von Pawel-Rammingen, Victor Nizet
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4bf1c23851d6480b83f7aafaefe65927
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4bf1c23851d6480b83f7aafaefe65927
record_format	dspace
spelling	oai:doaj.org-article:4bf1c23851d6480b83f7aafaefe659272021-11-15T15:43:09ZIgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>10.1128/mBio.00499-132150-7511https://doaj.org/article/4bf1c23851d6480b83f7aafaefe659272013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00499-13https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly contribute to the ability of the bacteria to survive white blood cell killing or produce invasive infection in the mouse. These data underscore the importance of correlating studies on virulence factor function with physiologic expression levels and the complexity of streptococcal pathogenesis and contribute to our overall understanding of how GAS causes disease.Cheryl Y. M. OkumuraEricka L. AndersonSimon DöhrmannDan N. TranJoshua OlsonUlrich von Pawel-RammingenVictor NizetAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Cheryl Y. M. Okumura Ericka L. Anderson Simon Döhrmann Dan N. Tran Joshua Olson Ulrich von Pawel-Rammingen Victor Nizet IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>
description	ABSTRACT 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. IMPORTANCE Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly contribute to the ability of the bacteria to survive white blood cell killing or produce invasive infection in the mouse. These data underscore the importance of correlating studies on virulence factor function with physiologic expression levels and the complexity of streptococcal pathogenesis and contribute to our overall understanding of how GAS causes disease.
format	article
author	Cheryl Y. M. Okumura Ericka L. Anderson Simon Döhrmann Dan N. Tran Joshua Olson Ulrich von Pawel-Rammingen Victor Nizet
author_facet	Cheryl Y. M. Okumura Ericka L. Anderson Simon Döhrmann Dan N. Tran Joshua Olson Ulrich von Pawel-Rammingen Victor Nizet
author_sort	Cheryl Y. M. Okumura
title	IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>
title_short	IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>
title_full	IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>
title_fullStr	IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>
title_full_unstemmed	IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>
title_sort	igg protease mac/ides is not essential for phagocyte resistance or mouse virulence of m1t1 group a <italic toggle="yes">streptococcus</italic>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/4bf1c23851d6480b83f7aafaefe65927
work_keys_str_mv	AT cherylymokumura iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic AT erickalanderson iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic AT simondohrmann iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic AT danntran iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic AT joshuaolson iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic AT ulrichvonpawelrammingen iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic AT victornizet iggproteasemacidesisnotessentialforphagocyteresistanceormousevirulenceofm1t1groupaitalictoggleyesstreptococcusitalic
_version_	1718427580961390592

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A <italic toggle="yes">Streptococcus</italic>

Ejemplares similares