The fibrinogen- and fibronectin-binding domains of Staphylococcus aureus fibronectin-binding protein A synergistically promote endothelial invasion and experimental endocarditis.

Details

Serval ID
serval:BIB_A1DA139E02C2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The fibrinogen- and fibronectin-binding domains of Staphylococcus aureus fibronectin-binding protein A synergistically promote endothelial invasion and experimental endocarditis.
Journal
Infection and Immunity
Author(s)
Piroth L., Que Y.A., Widmer E., Panchaud A., Piu S., Entenza J.M., Moreillon P.
ISSN
1098-5522 (Electronic)
ISSN-L
0019-9567
Publication state
Published
Issued date
2008
Volume
76
Number
8
Pages
3824-3831
Language
english
Abstract
Staphylococcus aureus experimental endocarditis relies on sequential fibrinogen binding (for valve colonization) and fibronectin binding (for endothelial invasion) conferred by peptidoglycan-attached adhesins. Fibronectin-binding protein A (FnBPA) reconciles these two properties--as well as elastin binding--and promotes experimental endocarditis by itself. Here we attempted to delineate the minimal subdomain of FnBPA responsible for fibrinogen and fibronectin binding, cell invasion, and in vivo endocarditis. A large library of truncated constructs of FnBPA was expressed in Lactococcus lactis and tested in vitro and in animals. A 127-amino-acid subdomain spanning the hinge of the FnBPA fibrinogen-binding and fibronectin-binding regions appeared necessary and sufficient to confer the sum of these properties. Competition with synthetic peptides could not delineate specific fibrinogen- and fibronectin-binding sites, suggesting that dual binding arose from protein folding, irrespective of clearly defined binding domains. Moreover, coexpressing the 127-amino-acid subdomain with remote domains of FnBPA further increased fibrinogen binding by > or =10 times, confirming the importance of domain interactions for binding efficacy. In animals, fibrinogen binding (but not fibronectin binding) was significantly associated with endocarditis induction, whereas both fibrinogen binding and fibronectin binding were associated with disease severity. Moreover, fibrinogen binding also combined with fibronectin binding to synergize the invasion of cultured cell lines significantly, a feature correlating with endocarditis severity. Thus, while fibrinogen binding and fibronectin binding were believed to act sequentially in colonization and invasion, they appeared unexpectedly intertwined in terms of both functional anatomy and pathogenicity (in endocarditis). This unforeseen FnBPA subtlety might bear importance for the development of antiadhesin strategies.
Keywords
Adhesins, Bacterial/genetics, Adhesins, Bacterial/metabolism, Animals, Cattle, Cell Line, Endocarditis, Bacterial/microbiology, Endothelial Cells/microbiology, Female, Fibrinogen/metabolism, Fibronectins/metabolism, Gene Expression, Lactococcus lactis/genetics, Protein Binding, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Rats, Sequence Deletion, Severity of Illness Index, Staphylococcus aureus/pathogenicity, Virulence Factors/genetics, Virulence Factors/metabolism
Pubmed
Web of science
Create date
20/03/2009 14:39
Last modification date
20/08/2019 15:07
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