Role of SraP, a Serine-Rich Surface Protein of Staphylococcus aureus, in binding to human platelets.
The binding of bacteria to platelets is a postulated central event in the pathogenesis of infective endocarditis. Platelet binding by Streptococcus gordonii is mediated in large part by GspB, a high-molecular-mass cell wall glycoprotein. Although Staphylococcus aureus has a GspB homolog (SraP), little is known about its function. SraP has a calculated molecular mass of 227 kDa and, like GspB, is predicted to contain an atypical N-terminal signal sequence, two serine-rich repeat regions (srr1 and srr2) separated by a nonrepeat region, and a C-terminal cell wall anchoring motif (LPDTG). To assess whether SraP contributes to platelet binding, we compared the binding to human platelets of S. aureus strain ISP479C and of an isogenic variant (strain PS767) in which sraP had been disrupted by allelic replacement. Platelet binding in vitro by PS767 was 47% +/- 17% (mean +/- standard deviation) lower than that of ISP479C (P < 0.001). In addition, a recombinant fragment of SraP containing srr1 and the nonrepeat region was found to bind platelets directly. Binding was saturable, suggesting a receptor-ligand interaction. When tested in a rabbit model of endocarditis, in which each animal was simultaneously infected with ISP479C and PS767 at a ratio of approximately 1:1, the titers of the mutant strain within vegetations were significantly lower than those of the parent strain at 1 and 24 h postinfection. These results indicate that SraP can mediate the direct binding of S. aureus to platelets and that the platelet-binding domain of this glycoprotein is located within its N-terminal region. Moreover, the expression of SraP appears to be a virulence determinant in endovascular infection.
Siboo
Ian R
IR
Division of Infectious Diseases, VA Medical Center (111W), 4150 Clement St., San Francisco, CA 94121, USA.
Chambers
Henry F
HF
Sullam
Paul M
PM
D018829:Adhesins, Bacterial / Q000502:physiology*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004697:Endocarditis, Bacterial / Q000209:etiology; D006031:Glycosylation; D006801:Humans; D011817:Rabbits; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014774:Virulence
D018829:Adhesins, Bacterial; C048165:adhesin, Staphylococcus aureus