Extracellular Fibrinogen-binding Protein, Efb, fromStaphylococcus aureus Blocks Platelet Aggregation Due to Its Binding to the α-Chain

Palma, Marco; Shannon, Oonagh; Quezada, Hernán Concha; Berg, Anders; Flock, Jan‐Ingmar

doi:10.1074/jbc.m104554200

Cited by 60 publications

(56 citation statements)

References 27 publications

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“…Interestingly, both Map and Efb were originally described as MSCRAMMS (microbial surface components recognizing adhesive matrix molecules) (72), a family of adhesins that mediate adhesion to host extracellular matrix components (18 -20, 24), emphasizing the importance of both parameters in establishing an infection. In the case of Efb, which inactivates complement-mediated lysis and phagocytosis (by binding to C3b) (17) and to delay clot formation and wound healing via a mechanism that involves fibrinogen binding (23,73), further illustrate the pleiotropic properties of many of these molecules.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the efb gene was present in all S. aureus isolates examined but not identified in any other staphylococcal species (21). Investigations into the roles of Efb in vivo have resulted in various hypotheses describing functions for Efb and include roles for Efb in potentiating S. aureus survival by delaying wound healing and by inhibiting platelet aggregation via its interactions with fibrinogen and the platelet receptor GPIIb/IIIa (23,55). Furthermore, these studies suggest that the fibrinogen binding domains were located at the N terminus of Efb and consist of two 22-amino acid repeats with homology to the fibrinogen binding domains of coagulase from S. aureus (20).…”

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confidence: 99%

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Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Lee

Liang

Höök

et al. 2004

Journal of Biological Chemistry

115

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The secreted Staphylococcus aureus extracellular fibrinogen-binding protein (Efb) is a virulence factor that binds to both the complement component C3b and fibrinogen. Our laboratory previously reported that by binding to C3b, Efb inhibited complement activation and blocked opsonophagocytosis. We have now located the Efb binding domain in C3b to the C3d fragment and determined a disassociation constant (K d ) of 0.24 M for the Efb-C3d binding using intrinsic fluorescence quenching assays. Using truncated, recombinant forms of Efb, we also demonstrate that the C3b binding region of Efb is located within the C terminus, in contrast to the fibrinogen binding domains that are located at the N-terminal end of the protein. Enzyme-linked immunosorbent assay-type binding assays demonstrated that recombinant Efb could bind to both C3b and fibrinogen simultaneously, forming a trimolecular complex and that the C-terminal region of Efb could inhibit complement activity in vitro. In addition, secondary structure analysis using circular dichroism spectroscopy revealed that the C-terminal, C3b binding region of Efb is composed primarily of ␣-helices, suggesting that this domain of Efb represents a novel type of C3b-binding protein.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Lee

Liang

Höök

et al. 2004

Journal of Biological Chemistry

115

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“…Efb plays a number of important roles during pathogenesis. The protein binds to host fibrinogen (Fg) and platelets and therefore blocks the binding of Fg to neutrophils and inhibits platelet aggregation (33)(34)(35). Efb also binds to C3b, which minimizes B and T cell responses, and inhibits complement-mediated opsonization and phagocytosis (36,37).…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Endocarditis-Associated Staphylococcus aureus

et al. 2013

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e Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninetyseven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted.

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“…Although Efb binds fibrinogen at two sites, which are the repeat regions at the N terminus and C terminus, only the N-terminal segment of the protein, containing the two 22-amino-acid repeats, could bind to soluble fibrinogen. The fact that Efb and staphylocoagulase compete for the same binding domain on fibrinogen might be due to their structural similarity (36). Staphylothrombin (a complex of staphylocoagulase and prothrombin) binds fibrinogen at the central region and repeat region.…”

Section: Structures Of Staphylocoagulasesmentioning

confidence: 99%

Structural Comparison of Ten Serotypes of Staphylocoagulases in Staphylococcus aureus

et al. 2005

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Staphylocoagulase detection is the hallmark of a Staphylococcus aureus infection. Ten different serotypes of staphylocoagulases have been reported to date. We determined the nucleotide sequences of seven staphylocoagulase genes (coa) and their surrounding regions to compare structures of all 10 staphylocoagulase serotypes, and we inferred their derivations. We found that all staphylocoagulases are comprised of six regions: signal sequence, D1 region, D2 region, central region, repeat region, and C-terminal sequence. Amino acids at both ends, 33 amino acids in the N terminal (the signal sequences and the seven N-terminal amino acids in the D1 region) and 5 amino acids in the C terminal, were exactly identical among the 10 serotypes. The central regions were conserved with identities between 80.6 and 94.1% and similarities between 82.8 and 94.6%. Repeat regions comprising tandem repeats of 27 amino acids with a 92% identity on average were polymorphic in the number of repeats. On the other hand, D1 regions other than the seven N-terminal amino acids and D2 regions were less homologous, with diverged identities from 41.5 to 84.5% and 47.0 to 88.9%, respectively, and similarities from 53.5 to 88.7% and 56.8 to 91.9%, respectively, although the predicted prothrombin-binding sites were conserved among them. In contrast, flanking regions of coa were highly homologous, with nucleotide identities of more than 97.1%. Phylogenetic relations among coa did not correlate with those among the flanking regions or housekeeping genes used for multilocus sequence typing. These data indicate that coa could be transmitted to S. aureus, while the less homologous regions in coa presumed to be responsible for different antigenicities might have evolved independently.

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Extracellular Fibrinogen-binding Protein, Efb, fromStaphylococcus aureus Blocks Platelet Aggregation Due to Its Binding to the α-Chain

Cited by 60 publications

References 27 publications

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Molecular Characterization of Endocarditis-Associated Staphylococcus aureus

Structural Comparison of Ten Serotypes of Staphylocoagulases in Staphylococcus aureus

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