Functional analysis of a murine monoclonal antibody against the repetitive region of the fibronectin-binding adhesins fibronectin-binding protein A and fibronectin-binding protein B from Staphylococcus aureus.
Citation:
Provenza G, Provenzano M, Visai L, Burke FM, Geoghegan JA, Stravalaci M, Gobbi M, Mazzini G, Arciola CR, Foster TJ, Speziale P, Functional analysis of a murine monoclonal antibody against the repetitive region of the fibronectin-binding adhesins fibronectin-binding protein A and fibronectin-binding protein B from Staphylococcus aureus., The FEBS journal, 277, 21, 2010, 4490-505Download Item:
Abstract:
Fibronectin-binding proteins A and B are multifunctional LPXTG staphylococcal adhesins, comprising an N-terminal region that binds fibrinogen and elastin, and a C-terminal domain that interacts with fibronectin. The C-terminal domain of fibronectin-binding protein A is organized into 11 tandem repeats, six of which bind the ligand with high affinity; other sites bind more weakly. Fibronectin-binding protein B has been postulated to harbor 10 rather than 11 repeats, but it contains the same number of highaffinity fibronectin-binding sites as fibronectin-binding protein A. In this study, we confirm this prediction and show that six of 10 sites bind with dissociation constants in the nanomolar range. We also found that the fulllength repetitive region of fibronectin-binding protein B stimulated the production of a mAb (15E11) that binds with high affinity to an epitope shared by repeats 9 and 10 from both adhesins. With the use of truncated fragments of repeat 9 of fibronectin-binding protein A, we mapped the antibody epitope to the N-terminal segment and the fibronectin-binding site to the C-terminal segment of the repeat. The distinct localization of the 15E11 epitope and the fibronectin-binding site suggests that the interfering effect of the antibody might result from steric hindrance or a conformational change in the structure that reduces the accessibility of fibronectin to its binding determinant. The epitope is well exposed on the surface of staphylococcal cells, as determined by genetic analyses, fluorescence microscopy, and flow cytometry. When incubated with cells of Staphylococcs aureus strains, 15E11 inhibits attachment of bacteria to surface-coated fibronectin by almost 70%.
Author's Homepage:
http://people.tcd.ie/tfosterhttp://people.tcd.ie/geoghejo
Description:
PUBLISHED
Author: FOSTER, TIMOTHY JAMES; GEOGHEGAN, JOAN
Type of material:
Journal ArticleCollections
Series/Report no:
The FEBS journal;277;
21;
Availability:
Full text availableMetadata
Show full item recordLicences:
Related items
Showing items related by title, author, creator and subject.
-
Molecular Interactions of Human Plasminogen with Fibronectin-binding Protein B (FnBPB), a Fibrinogen/Fibronectin-binding Protein from Staphylococcus aureus.
GEOGHEGAN, JOAN; FOSTER, TIMOTHY (2016)Staphylococcus aureus is a commensal bacterium that has the ability to cause superficial and deep-seated infections. Like several other invasive pathogens, S. aureus can capture plasminogen from the human host where it can ... -
Fibronectin‐binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcγRIIa receptor
FOSTER, TIMOTHY (2006)Staphylococcus aureus is a leading cause of infective endocarditis (IE). Platelet activation promoted by S. aureus resulting in aggregation and thrombus formation is an important step in the pathogenesis of IE. Here, we ... -
The A domain of fibronectin-binding protein B of Staphylococcus aureus contains a novel fibronectin binding site.
FOSTER, TIMOTHY JAMES (2011)The fibronectin‐binding proteins FnBPA and FnBPB are multifunctional adhesins than can also bind to fibrinogen and elastin. In this study, the N2N3 subdomains of region A of FnBPB were shown to bind fibrinogen with a similar ...