Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival

ABSTRACT Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM...

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Autores principales:	Marcus Fulde, Manfred Rohde, Andy Polok, Klaus T. Preissner, Gursharan Singh Chhatwal, Simone Bergmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2ba96b47f01640b18f7c7ea687a16259
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spelling	oai:doaj.org-article:2ba96b47f01640b18f7c7ea687a162592021-11-15T15:40:26ZCooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival10.1128/mBio.00629-122150-7511https://doaj.org/article/2ba96b47f01640b18f7c7ea687a162592013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00629-12https://doaj.org/toc/2150-7511ABSTRACT Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM, the M-like protein of S. canis, as the major receptor for miniplasminogen localized on the bacterial surface. The present study now characterizes the glycolytic enzyme enolase as an additional surface-exposed plasminogen-binding protein. According to its zoonotic properties, purified S. canis enolase binds to both human and canine plasminogen and facilitates degradation of aggregated fibrin matrices after activation with host-derived urokinase-type plasminogen activator (uPA). Unlike SCM, which binds to the C terminus of human plasminogen, the S. canis enolase interacts N terminally with the first four kringle domains of plasminogen, representing angiostatin. Radioactive binding analyses confirmed cooperative plasminogen recruitment to both surface-exposed enolase and SCM. Furthermore, despite the lack of surface protease activity via SpeB in S. canis, SCM is released and reassociated homophilically to surface-anchored SCM and heterophilically to surface-bound plasminogen. In addition to plasminogen-mediated antiphagocytic activity, reassociation of SCM to the bacterial surface significantly enhanced bacterial survival in phagocytosis analyses using human neutrophils. IMPORTANCE Streptococcal infections are a major issue in medical microbiology due to the increasing spread of antibiotic resistances and the limited availability of efficient vaccines. Surface-exposed glycolytic enzymes and M proteins have been characterized as major virulence factors mediating pathogen-host interaction. Since streptococcal infection mechanisms exert a subset of multicombinatorial processes, the investigation of synergistic activities mediated via different virulence factors has become a high priority. Our data clearly demonstrate that plasminogen recruitment to the Streptococcus canis surface via SCM and enolase in combination with SCM reassociation enhances bacterial survival by protecting against phagocytic killing. These data propose a new cooperative mechanism for prevention of phagocytic killing based on the synergistic activity of homophilic and heterophilic SCM binding in the presence of human plasminogen.Marcus FuldeManfred RohdeAndy PolokKlaus T. PreissnerGursharan Singh ChhatwalSimone BergmannAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Marcus Fulde Manfred Rohde Andy Polok Klaus T. Preissner Gursharan Singh Chhatwal Simone Bergmann Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival
description	ABSTRACT Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM, the M-like protein of S. canis, as the major receptor for miniplasminogen localized on the bacterial surface. The present study now characterizes the glycolytic enzyme enolase as an additional surface-exposed plasminogen-binding protein. According to its zoonotic properties, purified S. canis enolase binds to both human and canine plasminogen and facilitates degradation of aggregated fibrin matrices after activation with host-derived urokinase-type plasminogen activator (uPA). Unlike SCM, which binds to the C terminus of human plasminogen, the S. canis enolase interacts N terminally with the first four kringle domains of plasminogen, representing angiostatin. Radioactive binding analyses confirmed cooperative plasminogen recruitment to both surface-exposed enolase and SCM. Furthermore, despite the lack of surface protease activity via SpeB in S. canis, SCM is released and reassociated homophilically to surface-anchored SCM and heterophilically to surface-bound plasminogen. In addition to plasminogen-mediated antiphagocytic activity, reassociation of SCM to the bacterial surface significantly enhanced bacterial survival in phagocytosis analyses using human neutrophils. IMPORTANCE Streptococcal infections are a major issue in medical microbiology due to the increasing spread of antibiotic resistances and the limited availability of efficient vaccines. Surface-exposed glycolytic enzymes and M proteins have been characterized as major virulence factors mediating pathogen-host interaction. Since streptococcal infection mechanisms exert a subset of multicombinatorial processes, the investigation of synergistic activities mediated via different virulence factors has become a high priority. Our data clearly demonstrate that plasminogen recruitment to the Streptococcus canis surface via SCM and enolase in combination with SCM reassociation enhances bacterial survival by protecting against phagocytic killing. These data propose a new cooperative mechanism for prevention of phagocytic killing based on the synergistic activity of homophilic and heterophilic SCM binding in the presence of human plasminogen.
format	article
author	Marcus Fulde Manfred Rohde Andy Polok Klaus T. Preissner Gursharan Singh Chhatwal Simone Bergmann
author_facet	Marcus Fulde Manfred Rohde Andy Polok Klaus T. Preissner Gursharan Singh Chhatwal Simone Bergmann
author_sort	Marcus Fulde
title	Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival
title_short	Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival
title_full	Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival
title_fullStr	Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival
title_full_unstemmed	Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival
title_sort	cooperative plasminogen recruitment to the surface of <named-content content-type="genus-species">streptococcus canis</named-content> via m protein and enolase enhances bacterial survival
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/2ba96b47f01640b18f7c7ea687a16259
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Cooperative Plasminogen Recruitment to the Surface of <named-content content-type="genus-species">Streptococcus canis</named-content> via M Protein and Enolase Enhances Bacterial Survival

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