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Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion

Fibrinogen is an essential part of the blood coagulation cascade and a major component of the extracellular matrix in mammals. The interface between fibrinogen and bacterial pathogens is an important determinant of the outcome of infection. Here, we demonstrate that a canine host-restricted skin pat...

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Autores principales: Pickering, Amy C., Vitry, Pauline, Prystopiuk, Valeriia, Garcia, Brandon, Höök, Magnus, Schoenebeck, Jeffrey, Geoghegan, Joan A., Dufrêne, Yves F., Fitzgerald, J. Ross
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602291/
https://www.ncbi.nlm.nih.gov/pubmed/31216354
http://dx.doi.org/10.1371/journal.ppat.1007816
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author Pickering, Amy C.
Vitry, Pauline
Prystopiuk, Valeriia
Garcia, Brandon
Höök, Magnus
Schoenebeck, Jeffrey
Geoghegan, Joan A.
Dufrêne, Yves F.
Fitzgerald, J. Ross
author_facet Pickering, Amy C.
Vitry, Pauline
Prystopiuk, Valeriia
Garcia, Brandon
Höök, Magnus
Schoenebeck, Jeffrey
Geoghegan, Joan A.
Dufrêne, Yves F.
Fitzgerald, J. Ross
author_sort Pickering, Amy C.
collection PubMed
description Fibrinogen is an essential part of the blood coagulation cascade and a major component of the extracellular matrix in mammals. The interface between fibrinogen and bacterial pathogens is an important determinant of the outcome of infection. Here, we demonstrate that a canine host-restricted skin pathogen, Staphylococcus pseudintermedius, produces a cell wall-associated protein (SpsL) that has evolved the capacity for high strength binding to canine fibrinogen, with reduced binding to fibrinogen of other mammalian species including humans. Binding occurs via the surface-expressed N2N3 subdomains, of the SpsL A-domain, to multiple sites in the fibrinogen α-chain C-domain by a mechanism analogous to the classical dock, lock, and latch binding model. Host-specific binding is dependent on a tandem repeat region of the fibrinogen α-chain, a region highly divergent between mammals. Of note, we discovered that the tandem repeat region is also polymorphic in different canine breeds suggesting a potential influence on canine host susceptibility to S. pseudintermedius infection. Importantly, the strong host-specific fibrinogen-binding interaction of SpsL to canine fibrinogen is essential for bacterial aggregation and biofilm formation, and promotes resistance to neutrophil phagocytosis, suggesting a key role for the interaction during pathogenesis. Taken together, we have dissected a bacterial surface protein-ligand interaction resulting from the co-evolution of host and pathogen that promotes host-specific innate immune evasion and may contribute to its host-restricted ecology.
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spelling pubmed-66022912019-07-12 Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion Pickering, Amy C. Vitry, Pauline Prystopiuk, Valeriia Garcia, Brandon Höök, Magnus Schoenebeck, Jeffrey Geoghegan, Joan A. Dufrêne, Yves F. Fitzgerald, J. Ross PLoS Pathog Research Article Fibrinogen is an essential part of the blood coagulation cascade and a major component of the extracellular matrix in mammals. The interface between fibrinogen and bacterial pathogens is an important determinant of the outcome of infection. Here, we demonstrate that a canine host-restricted skin pathogen, Staphylococcus pseudintermedius, produces a cell wall-associated protein (SpsL) that has evolved the capacity for high strength binding to canine fibrinogen, with reduced binding to fibrinogen of other mammalian species including humans. Binding occurs via the surface-expressed N2N3 subdomains, of the SpsL A-domain, to multiple sites in the fibrinogen α-chain C-domain by a mechanism analogous to the classical dock, lock, and latch binding model. Host-specific binding is dependent on a tandem repeat region of the fibrinogen α-chain, a region highly divergent between mammals. Of note, we discovered that the tandem repeat region is also polymorphic in different canine breeds suggesting a potential influence on canine host susceptibility to S. pseudintermedius infection. Importantly, the strong host-specific fibrinogen-binding interaction of SpsL to canine fibrinogen is essential for bacterial aggregation and biofilm formation, and promotes resistance to neutrophil phagocytosis, suggesting a key role for the interaction during pathogenesis. Taken together, we have dissected a bacterial surface protein-ligand interaction resulting from the co-evolution of host and pathogen that promotes host-specific innate immune evasion and may contribute to its host-restricted ecology. Public Library of Science 2019-06-19 /pmc/articles/PMC6602291/ /pubmed/31216354 http://dx.doi.org/10.1371/journal.ppat.1007816 Text en © 2019 Pickering et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pickering, Amy C.
Vitry, Pauline
Prystopiuk, Valeriia
Garcia, Brandon
Höök, Magnus
Schoenebeck, Jeffrey
Geoghegan, Joan A.
Dufrêne, Yves F.
Fitzgerald, J. Ross
Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
title Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
title_full Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
title_fullStr Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
title_full_unstemmed Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
title_short Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
title_sort host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602291/
https://www.ncbi.nlm.nih.gov/pubmed/31216354
http://dx.doi.org/10.1371/journal.ppat.1007816
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