Abstract
Background Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the heart endothelium leading to vegetation formation (microbes, fibrin, platelets, and host cells attached to underlying endothelial tissue). Our previous research determined that enterococcal aggregation substance (AS) is an important virulence factor in causation of endocarditis, although endocarditis may occur in the absence of AS production. Production of AS by E. faecalis causes the organism to form aggregates through AS binding to enterococcal binding substance. In this study, we assessed the ability of IgGs and IgG Fabs against AS to provide protection against AS+ E. faecalis endocarditis.Methodology/Principal FindingsWhen challenged with AS+ E. faecalis, 10 rabbits actively immunized against AS+ E. faecalis developed more significant vegetations than 9 animals immunized against AS− E. faecalis, and 9/10 succumbed compared to 2/9 (p<0.005), suggesting enhanced aggregation by IgG contributes significantly to disease. IgG antibodies against AS also enhanced enterococcal aggregation as tested in vitro. In contrast, Fab fragments of IgG from rabbits immunized against purified AS, when passively administered to rabbits (6/group) immediately before challenge with AS+ E. faecalis, reduced total vegetation (endocarditis lesion) microbial counts (7.9×106 versus 2.0×105, p = 0.02) and size (40 mg versus 10, p = 0.05). In vitro, the Fabs prevented enterococcal aggregation.Conclusions/SignificanceThe data confirm the role of AS in infective endocarditis formation and suggest that use of Fabs against AS will provide partial protection from AS+ E. faecalis illness.
Highlights
Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the endothelium of the heart [1,2]
We previously showed that isogenic AS2 organisms cause more inflammation pericardially compared to aggregation substance (AS)+ organisms when both organisms are injected into the hearts of rabbits [5,14]
Having established that AS contributes to the virulence of E. faecalis through our studies and those of others, we attempted to interfere with AS activity, and possibly reduce the severity of endocarditis
Summary
Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the endothelium of the heart [1,2]. The characteristic endocarditis lesions are referred to as vegetations, which appear as nodules containing microbes, fibrin, platelets, and host cells attached to underlying endothelial tissue [3]. Previous studies have determined that enterococcal aggregation substance (AS), not required for enterococci to produce endocarditis, when present contributes significantly to the ability of E. faecalis to cause endocarditis [5,6,7]. AS is a large (137 kDa) surface-exposed protein encoded by pheromone-responsive, conjugative plasmids This protein contributes to formation of large bacterial cell aggregates through binding to enterococcal binding substance (EBS), a component of which appears to include lipoteichoic acid [8]. Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the heart endothelium leading to vegetation formation (microbes, fibrin, platelets, and host cells attached to underlying endothelial tissue). We assessed the ability of IgGs and IgG Fabs against AS to provide protection against AS+ E. faecalis endocarditis
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