title: Role of the sar locus of Staphylococcus aureus in induction of endocarditis in rabbits.
abstract: A regulatory locus on the Staphylococcus aureus chromosome, designated sar, is involved in the expression of cell wall proteins, some of which are potentially important in the pathogenesis of endocarditis. For instance, mutant 11D2 (sar::Tn917LTV1) was found to bind substantially less to matrix proteins (i.e., fibrinogen and fibronectin) than parent strain DB. Remarkably, these two strains did not differ in other phenotypes considered important in the initiation of endocarditis (e.g., binding to platelets and resistance to platelet-derived microbicidal proteins). The isogenic pair were compared for pathogenicity in a rabbit endocarditis model. There were significant differences in infectivity rates between the two strains (71 and 88% for DB versus 17 and 42% for mutant 11D2 at inocula of 10(3) and 10(4) CFU, respectively). In early adherence studies, parent DB adhered substantially better than the mutant to valvular vegetations at an inoculum of 10(6) CFU (P = 0.05). Southern blot analysis of colonies indicated that the location of the Tn917LTV1 insert in mutant 11D2 remained stable after animal passage. In vitro adherence assays revealed that mutant 11D2 was less adherent to cultured human endothelium than parent DB. These studies suggest that the sar locus is involved in the initial adherence of S. aureus to the fibrin-platelet-endothelium matrix on damaged valvular endothelium.
authors.affiliation: Laboratory of Bacteriology and Immunology, Rockefeller University, New York, New York 10021.
authors.forename: A L
authors.initials: AL
authors.lastname: Cheung
authors.forename: M R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: P M
authors.initials: PM
authors.lastname: Sullam
authors.forename: M D
authors.initials: MD
authors.lastname: Witt
authors.forename: A S
authors.initials: AS
authors.lastname: Bayer
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D004697:Endocarditis, Bacterial / Q000209:etiology*; D004730:Endothelium, Vascular / Q000382:microbiology; D006801:Humans; D011817:Rabbits; D013203:Staphylococcal Infections / Q000209:etiology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity