ROLE OF THE SAR LOCUS OF STAPHYLOCOCCUS-AUREUS IN INDUCTION OF ENDOCARDITIS IN RABBITS

A regulatory locus on the Staphylococcus aureus chromosome, designated sar, is involved in the expression of cell wall proteins, some of whi ch 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 paren t strain DB. Remarkably, these two strains did not differ in other phe notypes considered important in the initiation of endocarditis (e.g., binding to platelets and resistance to platelet-derived microbicidal p roteins). The isogenic pair were compared for pathogenicity in a rabbi t endocarditis model. There were significant differences in infectivit y rates between the two strains (71 and 88% for DB versus 17 and 42% f or mutant 11D2 at inocula of 10(3) and 10(4) CFU, respectively). In ea rly 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 th e Tn917LTV1 insert in mutant 11D2 remained stable after animal passage . In vitro adherence assays revealed that mutant 11D2 was less adheren t to cultured human endothelium than parent DB. These studies suggest that the sar locus is involved in the initial adherence of S. aureus t o the fibrin-platelet-endothelium matrix on damaged valvular endotheli um.