Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils

ABSTRACT Subversion of heparan sulfate proteoglycans (HSPGs) is thought to be a common virulence mechanism shared by many microbial pathogens. The prevailing assumption is that pathogens co-opt HSPGs as cell surface attachment receptors or as inhibitors of innate host defense. However, there are few...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Akiko Jinno, Atsuko Hayashida, Howard F. Jenkinson, Pyong Woo Park
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	extracellular matrix host-pathogen interactions keratitis proteoglycans syndecans Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/28f383a3db294b18b5ef0846687a0eb3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:28f383a3db294b18b5ef0846687a0eb3
record_format	dspace
spelling	oai:doaj.org-article:28f383a3db294b18b5ef0846687a0eb32021-11-15T15:55:43ZSyndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils10.1128/mBio.01907-202150-7511https://doaj.org/article/28f383a3db294b18b5ef0846687a0eb32020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01907-20https://doaj.org/toc/2150-7511ABSTRACT Subversion of heparan sulfate proteoglycans (HSPGs) is thought to be a common virulence mechanism shared by many microbial pathogens. The prevailing assumption is that pathogens co-opt HSPGs as cell surface attachment receptors or as inhibitors of innate host defense. However, there are few data that clearly support this idea in vivo. We found that deletion of syndecan-1 (Sdc1), a major cell surface HSPG of epithelial cells, causes a gain of function in a mouse model of scarified corneal infection, where Sdc1−/− corneas were significantly less susceptible to Streptococcus pneumoniae infection. Administration of excess Sdc1 ectodomains significantly inhibited S. pneumoniae corneal infection, suggesting that Sdc1 promotes infection as a cell surface attachment receptor. However, S. pneumoniae did not interact with Sdc1 and Sdc1 was shed upon S. pneumoniae infection, indicating that Sdc1 does not directly support S. pneumoniae adhesion. Instead, Sdc1 promoted S. pneumoniae adhesion by driving the assembly of fibronectin (FN) fibrils in the corneal basement membrane to which S. pneumoniae attaches when infecting injured corneas. S. pneumoniae specifically bound to corneal FN via PavA, and PavA deletion significantly attenuated S. pneumoniae virulence in the cornea. Excess Sdc1 ectodomains inhibited S. pneumoniae corneal infection by binding to the Hep II domain and interfering with S. pneumoniae PavA binding to FN. These findings reveal a previously unknown virulence mechanism of S. pneumoniae where key extracellular matrix (ECM) interactions and structures that are essential for host cell homeostasis are exploited for bacterial pathogenesis. IMPORTANCE Bacterial pathogens have evolved several ingenious mechanisms to subvert host cell biology for their pathogenesis. Bacterial attachment to the host ECM establishes a niche to grow and is considered one of the critical steps of infection. This pathogenic mechanism entails coordinated assembly of the ECM by the host to form the ECM structure and organization that are specifically recognized by bacteria for their adhesion. We serendipitously discovered that epithelial Sdc1 facilitates the assembly of FN fibrils in the corneal basement membrane and that this normal biological function of Sdc1 has detrimental consequences for the host in S. pneumoniae corneal infection. Our studies suggest that bacterial subversion of the host ECM is more complex than previously appreciated.Akiko JinnoAtsuko HayashidaHoward F. JenkinsonPyong Woo ParkAmerican Society for Microbiologyarticleextracellular matrixhost-pathogen interactionskeratitisproteoglycanssyndecansMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular matrix host-pathogen interactions keratitis proteoglycans syndecans Microbiology QR1-502
spellingShingle	extracellular matrix host-pathogen interactions keratitis proteoglycans syndecans Microbiology QR1-502 Akiko Jinno Atsuko Hayashida Howard F. Jenkinson Pyong Woo Park Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils
description	ABSTRACT Subversion of heparan sulfate proteoglycans (HSPGs) is thought to be a common virulence mechanism shared by many microbial pathogens. The prevailing assumption is that pathogens co-opt HSPGs as cell surface attachment receptors or as inhibitors of innate host defense. However, there are few data that clearly support this idea in vivo. We found that deletion of syndecan-1 (Sdc1), a major cell surface HSPG of epithelial cells, causes a gain of function in a mouse model of scarified corneal infection, where Sdc1−/− corneas were significantly less susceptible to Streptococcus pneumoniae infection. Administration of excess Sdc1 ectodomains significantly inhibited S. pneumoniae corneal infection, suggesting that Sdc1 promotes infection as a cell surface attachment receptor. However, S. pneumoniae did not interact with Sdc1 and Sdc1 was shed upon S. pneumoniae infection, indicating that Sdc1 does not directly support S. pneumoniae adhesion. Instead, Sdc1 promoted S. pneumoniae adhesion by driving the assembly of fibronectin (FN) fibrils in the corneal basement membrane to which S. pneumoniae attaches when infecting injured corneas. S. pneumoniae specifically bound to corneal FN via PavA, and PavA deletion significantly attenuated S. pneumoniae virulence in the cornea. Excess Sdc1 ectodomains inhibited S. pneumoniae corneal infection by binding to the Hep II domain and interfering with S. pneumoniae PavA binding to FN. These findings reveal a previously unknown virulence mechanism of S. pneumoniae where key extracellular matrix (ECM) interactions and structures that are essential for host cell homeostasis are exploited for bacterial pathogenesis. IMPORTANCE Bacterial pathogens have evolved several ingenious mechanisms to subvert host cell biology for their pathogenesis. Bacterial attachment to the host ECM establishes a niche to grow and is considered one of the critical steps of infection. This pathogenic mechanism entails coordinated assembly of the ECM by the host to form the ECM structure and organization that are specifically recognized by bacteria for their adhesion. We serendipitously discovered that epithelial Sdc1 facilitates the assembly of FN fibrils in the corneal basement membrane and that this normal biological function of Sdc1 has detrimental consequences for the host in S. pneumoniae corneal infection. Our studies suggest that bacterial subversion of the host ECM is more complex than previously appreciated.
format	article
author	Akiko Jinno Atsuko Hayashida Howard F. Jenkinson Pyong Woo Park
author_facet	Akiko Jinno Atsuko Hayashida Howard F. Jenkinson Pyong Woo Park
author_sort	Akiko Jinno
title	Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils
title_short	Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils
title_full	Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils
title_fullStr	Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils
title_full_unstemmed	Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils
title_sort	syndecan-1 promotes <named-content content-type="genus-species">streptococcus pneumoniae</named-content> corneal infection by facilitating the assembly of adhesive fibronectin fibrils
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/28f383a3db294b18b5ef0846687a0eb3
work_keys_str_mv	AT akikojinno syndecan1promotesnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontentcornealinfectionbyfacilitatingtheassemblyofadhesivefibronectinfibrils AT atsukohayashida syndecan1promotesnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontentcornealinfectionbyfacilitatingtheassemblyofadhesivefibronectinfibrils AT howardfjenkinson syndecan1promotesnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontentcornealinfectionbyfacilitatingtheassemblyofadhesivefibronectinfibrils AT pyongwoopark syndecan1promotesnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontentcornealinfectionbyfacilitatingtheassemblyofadhesivefibronectinfibrils
_version_	1718427141135138816

Syndecan-1 Promotes <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils

Ejemplares similares