Table 3.
Characteristics of the Included Studies.
| First Author/Year/Ref | Type of Study | Cohort | Aims | Finding |
|---|---|---|---|---|
| Que et al. (2005) J. Exp. Med. [73] |
Animal model Single Center (Switzerland) |
Rat model of IE induced | To study valve colonization with experimental endocarditis. To evaluate the role of ClfA and FnBPA positive lactococci | Fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo |
| Edwards et al. (2012) PLoS ONE [74] |
Human Single Center (UK) |
Blood sample | To study in vivo role of Eap to interact with host glyco-proteins | Eap expressing strains cause a more severe infection, demonstrating its role in invasive disease. Increased level of TNFα and gC1qR/p33 expression |
| Veloso et al. (2013) Infect. Immun. [76] |
Animal model Single Center (Switzerland) |
Rat model of induced IE 10(6) CFU L. lactis pIL253 vs. Recombinant L. lactis (ClfA, FnbpA, BCD, or SdrE) |
To explore the contributions of S. aureus virulence factors to the initiation of IE | Fibrinogen binding in the initiation of S. aureus IE. Activation of platelet aggregation or an inflammatory response may contribute to or promote the development of EI |
| Thomas et al. (2021) mBio [77] |
Animal model Single Center (USA) |
Rat model of IE induced | To identify proteins with significant amino acid identities to vWbp | Protein homologous to the C-terminal of vWbp was identified. Its role in Fg shield assembly and binds |
| Hussain et al. (2002) Infect. Immun. [78] |
In vitro Single center (Germany) |
S. aureus Newman cultures vs. Control mutant |
To investigate the role of Eap by constructing a stable eap::ermB deletion | Eap may contribute to pathogenicity by promoting adhesion of whole staphylococcal cells to complex eukaryotic substrates |
| Palankar et al. (2018) Int. J. Med. Microbiol. [79] |
In vitro Single center (Germany) |
S. aureus Mu50 | To investigate Eap subdomain and interaction with platelet | Eap subdomain Eap D3D4 specifically interacts and rapidly activates human platelets |
| Hussain et al. (2008) Infect. Immun. [80] |
In vitro Single center (Germany) |
S. aureus Newman cultures vs. S. aureus Wood 46 |
To investigate the interactions of full-length Eap and five recombinant tandem repeat domains with host proteins | More than one Eap tandem repeat domain is required for S. aureus agglutination, adherence, and cellular invasion but not for the stimulation of PBMC proliferation |
| Heying et al. (2007) Thromb. Haemost. [114] |
Human Single Center (Germany) |
S. aureus L. lactis culture cultured human EC |
To investigate the role of FnBPA, FnBPB ClfA to promote bacterial adherence to cultured human ECs | S. aureus FnBPs, but not ClfA, lead pathogenicity to non-pathogenic L. lactis. Adhesins (ICAM-1 and VCAM-1) evokes inflammation (interleukin-8) as well as procoagulant activity |
| Piroth et al. (2008) Infect. Immun. [115] |
Animal model Single Center (Switzerland) |
S. aureus L. lactis culture In vitro and in vivo |
To study the subdomain of FnBPA responsible for fibrinogen and fibronectin binding, cell invasion, and in vivo endocarditis | Fb binding combined with fibronectin binding to synergize the invasion of cultured cell lines is correlated with IE severity |
| Pappelbaum et al. (2013) Circulation [117] |
Human/Animal Single center (Germany) |
6 WT mice with VWF vs. 5 knockout mice vs. Cultured human EC |
Whether ULVWF mediates bacterial adherence | ULVWF contributes to the initial pathogenic step of S aureus-induced endocarditis in patients with an intact endothelium. Heparin or ADAMTS13 intervenes in decreasing ULVWF adherence |
| Claes et al. (2018) Thromb. Haemost. [119] |
Human/Animal Multicenter (Belgium pilot) |
L. lactis-clfA vs. L. lactis-fnbpA vs. Cultured human EC |
To study the influence of shear flow and plasma on the binding of ClfA and FnbpA | Pharmacological inhibition of ClfA-Fg interactions may constitute a valuable additive treatment in infective endocarditis |
| Ko et al. (2016) mBio [120] |
Animal model Single Center (USA) |
Rat model of IE induced | To identify variants of a linear Fg binding motif, present in Coa and Efb which are responsible for the Fg binding activities of these proteins | S. aureus coagulase can induce the formation of a fibrinogen shield in experimental abscess models which surrounds and protects bacteria in the microcolony from clearance |
| Niemann et al. (2021) mBio [125] |
Animal Multicenter (Germany) |
Rat model of IE induced in osteoblasts vs. epithelial cells |
To demonstrate that S. aureus was less engulfed in osteoblasts than in epithelial cells | Large differences of S. aureus uptake efficacy in different host cell types. In vivo differences between courses of bacterial infections and the localization of bacteria in different clinical settings mediated by α5β1-integrin |
| Pietrocola et al. (2020) J. Biol. Chem. [126] |
Animal Multicenter center (Italy pilot) |
Rat model of IE induced | To evaluate a variety of virulence factors that promote infection by S. aureus | Adherence to and invasion of epithelial and ECs by IsdB-expressing S. aureus cells was promoted by Vn, and an αvβ3 integrin-blocking mAb |
| Alfeo et al. (2021) Sci. Rep. [127] |
Animal Multicenter center (Italy pilot) |
Rat model of IE induced | To study IsdB protein and Vn binding Interacts with vWF | Importance of IsdB in adherence of S. aureus to the endothelium colonization and as potential therapeutic target |
| Ditkowski et al. (2021) J. Thorac. Cardiovasc. Surg. [129] |
Human Multicenter (Belgium pilot) |
5 graft tissues | To investigate contributions by platelets and plasma fibrinogen to IE initiation on various grafts used for valve replacement | Binding of plasma Fg to especially BJV grafts enables adhesion of single platelets via αIIbβ3. S aureus attaches from blood to activated bound platelet αIIbβ3 via plasma fibrinogen |
Abbreviations: ADAMTS13, a disintegrin and metalloproteinase with thrombospondin motifs 13; BJV, bovine jugular vein; ClfA, clumping factor A; Eap, S. aureus extracellular adhesion protein; EC, endothelial cell; Fc, fibrinogen; FnBPA, fibronectin-binding protein A; IsdB, iron-regulated surface determinant B protein; IL, interleukine; L. lactis, Lactococcus lactis; SdrE; mAb, monoclonal antibody; PBMC, peripheral blood mononuclear cells; TNF, tumor necrosis factor; ULVWF, ultra-large von Willebrand factor; Vn, extracellular matrix protein vitronectin; vWbp, von Willebrand factor-binding protein; vhp, vWbp homologous protein.