Fibrinogen and fibronectin binding cooperate for valve infection and invasion in <i>Staphylococcus aureus</i> experimental endocarditis

Que, Yok-Ai; Haefliger, Jacques‐Antoine; Piroth, Lionel; François, Patrice; Widmer, Eleonora; Entenza, José M.; Sinha, Bhanu; Herrmann, Mathias; Francioli, P.; Vaudaux, Pierre; Moreillon, Philippe

doi:10.1084/jem.20050125

Cited by 275 publications

(282 citation statements)

References 53 publications

Supporting

Mentioning

267

Contrasting

Unclassified

Order By: Relevance

“…Animal models of infective endocarditis suggest the importance of S. aureus/Fn interactions in disease progression (6), and here, we have shown that they are achieved through a highly unusual mechanism of protein-protein recognition. The large FnBR/ 2-5 F1 interfaces suggest that the design of small-molecule inhibitors of the S. aureus/Fn interaction will be challenging.…”

Section: Resultsmentioning

confidence: 93%

“…In FnBPA, which also binds fibrinogen, the fibrinogen-and Fn-binding regions (Fig. 1 A) appear to cooperate in disease progression, with the FnBR region being particularly associated with persistence of infection (6). FnBPA/Fn interactions both mediate S. aureus invasion of (7) and activate endothelial cells, evoking both the proinflammatory and procoagulant responses typical of infective endocarditis (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA in complex with fibronectin domains

Bingham

Rudino‐Pinera

Meenan

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

165

View full text Add to dashboard Cite

Staphylococcus aureus can adhere to and invade endothelial cells by binding to the human protein fibronectin (Fn). FnBPA and FnBPB, cell wall-attached proteins from S. aureus, have multiple, intrinsically disordered, high-affinity binding repeats (FnBRs) for Fn. Here, 30 years after the first report of S. aureus/Fn interactions, we present four crystal structures that together comprise the structures of two complete FnBRs, each in complex with four of the N-terminal modules of Fn. Each Ϸ40-residue FnBR forms antiparallel strands along the triple-stranded ␤-sheets of four sequential F1 modules ( 2-5 F1) with each FnBR/ 2-5 F1 interface burying a total surface area of Ϸ4,300 Å 2 . The structures reveal the roles of residues conserved between S. aureus and Streptococcus pyogenes FnBRs and show that there are few linker residues between FnBRs. The ability to form large intermolecular interfaces with relatively few residues has been proposed to be a feature of disordered proteins, and S. aureus/Fn interactions provide an unusual illustration of this efficiency.intrinsic disorder ͉ tandem ␤-zipper ͉ host-pathogen interaction S taphylococcus aureus is a dangerous human pathogen that causes a wide range of debilitating and life-threatening infections (1). Incidence of S. aureus resistance to antibiotics (2) makes the understanding of its mechanisms of pathogenesis imperative. S. aureus/Fn interactions were first reported 30 years ago, and an S. aureus Fn-binding protein was isolated and characterized Ϸ20 years ago (3). Our recent work has dissected the 363-residue C-terminal region of FnBPA into 11 FnBRs (4) (FnBPA1-11; Fig. 1 A and B), six of which bind the NTD (N-terminal domain) of Fn (comprising modules 1-5 F1) with dissociation constants in the nanomolar range (5). The Cterminal region of FnBPB, a second S. aureus Fn-binding protein, is very similar to FnBPA but lacks one of the shorter FnBRs (5). In FnBPA, which also binds fibrinogen, the fibrinogen-and Fn-binding regions (Fig. 1 A) appear to cooperate in disease progression, with the FnBR region being particularly associated with persistence of infection (6). FnBPA/Fn interactions both mediate S. aureus invasion of (7) and activate endothelial cells, evoking both the proinflammatory and procoagulant responses typical of infective endocarditis (8). FnBPAs ability to mediate platelet activation, a key step in thrombus formation, is also likely to play a role in cardiovascular disease (9) and FnBPA has been implicated in cardiac device infections through its ability to mediate S. aureus attachment to implanted prosthetic materials (10). We previously predicted that in Fn-BPA each FnBR binds a string of three or four F1 modules in the NTD of Fn through a longer version of the tandem ␤-zipper mechanism that we discovered in Streptococcus dysgalactiae interactions with 1 F1 2 F1 (4). Results and DiscussionCrystal Structure of FnBPA-1/ 2-5 F1. Fig. 1C shows two F1 module pair/peptide structures that together comprise the structure of the most N-terminal S. aureus FnBR (...

show abstract

Section: Resultsmentioning

confidence: 93%

mentioning

confidence: 99%

Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA in complex with fibronectin domains

Bingham

Rudino‐Pinera

Meenan

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

165

View full text Add to dashboard Cite

show abstract

“…This explains why there is no simple approach to assess the presence or absence of each individual pathogenic feature along the successive steps of infection. Previous experiments in which specific genes were inactivated were sometimes difficult to interpret, particularly when bacteria were equipped with multiple genes encoding redundant or complementary functions (13,40,53). Moreover, gene regulation may vary between in vitro and in vivo conditions (23).…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Transcriptomic Profiling of Staphylococcus aureus Surface LPXTG-proteins: Correlation with agr Genotypes and Adherence Phenotypes

Ythier

Resch

Waridel

et al. 2012

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

“…For example, several surface proteins of Gram-positive bacteria, mediating platelet aggregation, have been demonstrated to be important for virulence in animal models of IE [22][23][24][25]. However, platelet activation by Grampositive pathogens most often requires specific host IgG, perhaps indicating that platelet activation should be regarded as a host immune response.…”

Section: Discussionmentioning

confidence: 99%

Clinical isolates of Enterococcus faecalis aggregate human platelets

Rasmussen

Johansson

Söbirk

et al. 2010

Microbes and Infection

View full text Add to dashboard Cite

Many endocarditis pathogens activate human platelets and this has been proposed to contribute to virulence. Here we report for the first time that many clinical isolates of Enterococcus faecalis, a common pathogen in infective endocarditis, aggregate human platelets. 84 isolates from human blood and urine were screened for their ability to aggregate platelets from four different donors. Platelet aggregation occurred for between 11 and 65 % of isolates depending on the donor. In one donor, a significantly larger proportion of isolates from blood than from urine caused platelet aggregation. Median time to aggregation was 11 minutes and had a tendency to be shorter for blood isolates as compared to urine isolates.Immunoglobulin G (IgG) was shown to be essential in mediating activation and aggregation. Platelet aggregation could be abolished by an IgG-specific proteinase (IdeS), by an antibody blocking FcRIIa on platelets, or by preabsorption of plasma with an E. faecalis isolate. Fibrinogen binding to bacteria or platelets does not contribute to platelet activation or aggregation under our experimental conditions. These results indicate that platelet activation and aggregation by E. faecalis is dependent on both host and bacterial factors and that it may be involved in the pathogenesis of invasive disease with this organism.

show abstract

Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis

Cited by 275 publications

References 53 publications

Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA in complex with fibronectin domains

Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA in complex with fibronectin domains

Proteomic and Transcriptomic Profiling of Staphylococcus aureus Surface LPXTG-proteins: Correlation with agr Genotypes and Adherence Phenotypes

Clinical isolates of Enterococcus faecalis aggregate human platelets

Contact Info

Product

Resources

About