Al. Cheung et al., DIMINISHED VIRULENCE OF A SAR(-) AGR(-) MUTANT OF STAPHYLOCOCCUS-AUREUS IN THE RABBIT MODEL OF ENDOCARDITIS/, The Journal of clinical investigation, 94(5), 1994, pp. 1815-1822
Microbial pathogenicity in Staphylococcus aureus is a complex process
involving a number of virulence genes that are regulated by global reg
ulatory systems including sar and agr. To evaluate the roles of these
two loci in virulence, we constructed sar(-)lagr(-) mutants of strains
RN6390 and RN450 and compared their phenotypic profiles to the corres
ponding single sar(-) and agr(-) mutants and parents. The secretion of
all hemolysins was absent in the sar(-)lagr(-) mutants while residual
beta-hemolysin activity remained in single agr(-) mutants. The fibron
ectin binding capacity was significantly diminished in both single sar
(-) mutants and double mutants when compared with parents while the re
duction in fibrinogen binding capacity in the double mutants was modes
t. In the rabbit endocarditis model, there was a significant decrease
in both infectivity rates and intravegetation bacterial densities with
the double mutant as compared to the parent (RN6390) at 10(3)-10(6) C
FU inocula despite comparable levels of early bacteremia among various
challenge groups. Notably, fewer bacteria in the double mutant group
adhered to valvular vegetations at 30 min after challenge (10(6) CFU)
than the parent group. These studies suggest that both the sar and agr
loci are involved in initial valvular adherence, intravegetation pers
istence and multiplication of S. aureus in endocarditis.