Gelatinase Contributes to the Pathogenesis of Endocarditis Caused by Enterococcus faecalis

Abstract

ABSTRACT The Gram-positive pathogen Enterococcus faecalis is a leading agent of nosocomial infections, including urinary tract infections, surgical site infections, and bacteremia. Among the infections caused by E. faecalis , endocarditis remains a serious clinical manifestation and unique in that it is commonly acquired in a community setting. Infective endocarditis is a complex disease, with many host and microbial components contributing to the formation of bacterial biofilm-like vegetations on the aortic valve and adjacent areas within the heart. In the current study, we compared the pathogenic potential of the vancomycin-resistant E. faecalis V583 and three isogenic protease mutants (Δ gelE , Δ sprE , and Δ gelE Δ sprE mutants) in a rabbit model of enterococcal endocarditis. The bacterial burdens displayed by GelE − mutants (Δ gelE and Δ gelE Δ sprE mutants) in the heart were significantly lower than those of V583 or the SprE − mutant. Vegetations on the aortic valve infected with GelE − mutants (Δ gelE and Δ gelE Δ sprE mutants) also showed a significant increase in deposition of fibrinous matrix layer and increased chemotaxis of inflammatory cells. In support of a role for proteolytic modulation of the immune response to E. faecalis , we also demonstrate that GelE can cleave the anaphylatoxin complement C5a and that this proteolysis leads to decreased neutrophil migration in vitro . In vivo , a decreased heterophil (neutrophil-like cell) migration was observed at tissue sites infected with GelE-producing strains but not at those infected with SprE-producing strains. Taken together, these observations suggest that of the two enterococcal proteases, gelatinase is the principal mediator of pathogenesis in endocarditis.