Fibronectin-binding proteins and clumping factor A in Staphylococcus aureus experimental endocarditis: FnBPA is sufficient to activate human endothelial cells.
Surface molecules of Staphylococcus aureus are involved in the colonization of vascular endothelium which is a crucial primary event in the pathogenesis of infective endocarditis (IE). The ability of these molecules to also launch endothelial procoagulant and proinflammatory responses, which characterize IE, is not known. In the present study we investigated the individual capacities of three prominent S. aureus surface molecules; fibronectin-binding protein A (FnBPA) and B (FnBPB) and clumping factor A (ClfA), to promote bacterial adherence to cultured human endothelial cells (ECs) and to activate phenotypic and functional changes in these ECs. Non-invasive surrogate bacterium Lactococcus lactis, which, by gene transfer, expressed staphylococcal FnBPA, FnBPB or ClfA molecules were used. Infection of ECs increased 50- to 100-fold with FnBPA- or FnBPB-positive recombinant lactococci. This coincided with EC activation, interleukin-8 secretion and surface expression of ICAM-1 and VCAM-1 and concomitant monocyte adhesion. Infection with ClfA-positive lactococci did not activate EC. FnBPA-positive L. lactis also induced a prominent tissue factor-dependent endothelial coagulation response that was intensified by cell-bound monocytes. Thus S. aureus FnBPs, but not ClfA, confer invasiveness and pathogenicity to non-pathogenic L. lactis organisms indicating that bacterium-EC interactions mediated by these adhesins are sufficient to evoke inflammation as well as procoagulant activity at infected endovascular sites.
Heying
Ruth
R
Department of Paediatric Cardiology, University Children's Hospital, Duesseldorf, Germany.
van de Gevel
Joke
J
Que
Yok-Ai
YA
Moreillon
Philippe
P
Beekhuizen
Henry
H
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D001777:Blood Coagulation; D002448:Cell Adhesion; D002478:Cells, Cultured; D003030:Coagulase / Q000235:genetics / Q000378:metabolism*; D004697:Endocarditis, Bacterial / Q000378:metabolism* / Q000382:microbiology; D042783:Endothelial Cells / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D011994:Recombinant Proteins / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018829:Adhesins, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D016209:Interleukin-8; C509820:MSCRAMM proteins, Staphylococcus; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; C078635:fibronectin-binding proteins, bacterial; D018799:Intercellular Adhesion Molecule-1; D013925:Thromboplastin