T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitate...

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Autores principales:	Yi-Hsuan Chen, Shao-Hui Li, Yao-Cheng Yang, Shu-Hao Hsu, Victor Nizet, Yung-Chi Chang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Streptococcus pyogenes group A Streptococcus pilus T antigen haptoglobin innate immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e64910c3fde843fbae431e970f2fedf2
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spelling	oai:doaj.org-article:e64910c3fde843fbae431e970f2fedf22021-11-15T15:56:44ZT4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>10.1128/mBio.01580-202150-7511https://doaj.org/article/e64910c3fde843fbae431e970f2fedf22020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01580-20https://doaj.org/toc/2150-7511ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses. IMPORTANCE Group A Streptococcus (GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.Yi-Hsuan ChenShao-Hui LiYao-Cheng YangShu-Hao HsuVictor NizetYung-Chi ChangAmerican Society for MicrobiologyarticleStreptococcus pyogenesgroup A StreptococcuspilusT antigenhaptoglobininnate immunityMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pyogenes group A Streptococcus pilus T antigen haptoglobin innate immunity Microbiology QR1-502
spellingShingle	Streptococcus pyogenes group A Streptococcus pilus T antigen haptoglobin innate immunity Microbiology QR1-502 Yi-Hsuan Chen Shao-Hui Li Yao-Cheng Yang Shu-Hao Hsu Victor Nizet Yung-Chi Chang T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
description	ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses. IMPORTANCE Group A Streptococcus (GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.
format	article
author	Yi-Hsuan Chen Shao-Hui Li Yao-Cheng Yang Shu-Hao Hsu Victor Nizet Yung-Chi Chang
author_facet	Yi-Hsuan Chen Shao-Hui Li Yao-Cheng Yang Shu-Hao Hsu Victor Nizet Yung-Chi Chang
author_sort	Yi-Hsuan Chen
title	T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_short	T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_full	T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_fullStr	T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_full_unstemmed	T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_sort	t4 pili promote colonization and immune evasion phenotypes of nonencapsulated m4 <named-content content-type="genus-species">streptococcus pyogenes</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/e64910c3fde843fbae431e970f2fedf2
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T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 <named-content content-type="genus-species">Streptococcus pyogenes</named-content>

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