Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
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Authors: | Patrick M. Schlievert Olivia N. Chuang-Smith Marnie L. Peterson Laura C. C. Cook Gary M. Dunny |
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Affiliation: | Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.;National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States of America |
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Abstract: | BackgroundEnterococcus 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. |
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