Diminished platelet binding in vitro by Staphylococcus aureus is associated with reduced virulence in a rabbit model of infective endocarditis.
The direct binding of platelets by bacteria is a postulated central mechanism in the pathogenesis of endocarditis. To address the role of binding more definitively, we employed Tn551 insertional mutagenesis of Staphylococcus aureus parental strain ISP479 to generate an isogenic variant (strain PS12) that bound platelets minimally. As compared with the binding of ISP479, the binding of PS12 to platelet monolayers was reduced by 67.2%. Similarly, the binding of PS12 to platelets in suspension was reduced by 71.3%, as measured by flow cytometry. The low-binding phenotype was transducible into both ISP479 and S. aureus Newman. Southern blotting indicated that a single copy of Tn551 was inserted within the chromosomes of PS12 and the transductants. When tested in a rabbit model, animals inoculated with PS12 were significantly less likely to develop endocarditis and had lower densities of organisms (CFU per gram) within vegetations and a decreased incidence of renal abscess formation, as compared with animals inoculated with the parental strain. The diminished virulence of PS12 was not attributable to a reduction in the initial attachment of organisms to the damaged endocardium, since 30 min after inoculation, PS12-infected animals had microbial densities on the valve surface comparable to those seen with the parental strain. These results indicate that the direct binding of Staphylococcus aureus to platelets is a major determinant of virulence in the pathogenesis of endocarditis. Staphylococcus-platelet binding appears to be critical for pathogenetic events occurring after the initial colonization of the valve surface, such as vegetation formation and septic embolization.
Sullam
P M
PM
Department of Medicine, Veterans Affairs Medical Center and University of California, San Francisco 94121, USA. sullam@sanfrancisco.va.gov
Bayer
A S
AS
Foss
W M
WM
Cheung
A L
AL
D000818:Animals; D001422:Bacterial Adhesion; D001792:Blood Platelets / Q000382:microbiology*; D004697:Endocarditis, Bacterial / Q000097:blood / Q000382:microbiology*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000097:blood / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D014774:Virulence