ROLE OF STAPHYLOCOCCUS-AUREUS COAGULASE AND CLUMPING FACTOR IN PATHOGENESIS OF EXPERIMENTAL ENDOCARDITIS

The pathogenic role of staphylococcal coagulase and clumping factor wa s investigated in the rat model of endocarditis. The coagulase-produci ng and clumping factor-producing parent strain Staphylococcus aureus N ewman and a series of mutants defective in either coagulase, clumping factor, or both were tested for their ability (i) to attach in vitro t o either rat fibrinogen or platelet-fibrin clots and (ii) to produce e ndocarditis in rats with catheter-induced aortic vegetations, In vitro , the clumping factor-defective mutants were up to 100 times less able than the wild type strain to attach to fibrinogen and also significan tly less adherent than the parents to platelet-fibrin clots. Coagulase -defective mutants, in contrast, were not altered in their in vitro ad herence phenotype, The rate of in vivo infection was inoculum dependen t. Clumping factor-defective mutants produced ca, 50% less endocarditi s than the parent organisms when injected at inoculum sizes infecting, respectively, 40 and 80% (ID40 and ID80, respectively) of rats with t he wild-type strain, This was a trend at the ID40 but was statisticall y significant at the ID80 (P < 0.05), Coagulase defective bacteria wer e not affected in their infectivity, Complementation of a clumping fac tor-defective mutant with a copy of the wild-type clumping factor gene restored both its in vitro adherence and its in vivo infectivity, The se results show that clumping factor plays a specific role in the path ogenesis of S, aureus endocarditis, Nevertheless, the rate of endocard itis with clumping factor-defective mutants increased with larger inoc ula, indicating the contribution of additional pathogenic determinants in the infective process.