Role of Staphylococcus aureus coagulase and clumping factor in pathogenesis of experimental endocarditis.
The pathogenic role of staphylococcal coagulase and clumping factor was investigated in the rat model of endocarditis. The coagulase-producing and clumping factor-producing parent strain Staphylococcus aureus Newman and a series of mutants defective in either coagulase, clumping factor, or both were tested for their ability (i) to attach in vitro to either rat fibrinogen or platelet-fibrin clots and (ii) to produce endocarditis 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 significantly less adherent than the parents to platelet-fibrin clots. Coagulase-defective mutants, in contrast, were not altered in their in vitro adherence phenotype. The rate of in vivo infection was inoculum dependent. Clumping factor-defective mutants produced ca. 50% less endocarditis than the parent organisms when injected at inoculum sizes infecting, respectively, 40 and 80% (ID40 and ID80, respectively) of rats with the wild-type strain. This was a trend at the ID40 but was statistically significant at the ID80 (P < 0.05). Coagulase-defective bacteria were not affected in their infectivity. Complementation of a clumping factor-defective mutant with a copy of the wild-type clumping factor gene restored both its in vitro adherence and its in vivo infectivity. These results show that clumping factor plays a specific role in the pathogenesis of S. aureus endocarditis. Nevertheless, the rate of endocarditis with clumping factor-defective mutants increased with larger inocula, indicating the contribution of additional pathogenic determinants in the infective process.
Moreillon
P
P
Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Entenza
J M
JM
Francioli
P
P
McDevitt
D
D
Foster
T J
TJ
François
P
P
Vaudaux
P
P
D000818:Animals; D001422:Bacterial Adhesion; D003030:Coagulase / Q000502:physiology*; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D005260:Female; D009154:Mutation; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000201:enzymology / Q000382:microbiology*
D003030:Coagulase