Enterococcus faecalis endocarditis severity in rabbits is reduced by IgG Fabs interfering with aggregation substance.
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.


RESULTS
When 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 x 10⁶ versus 2.0 x 10⁵, p = 0.02) and size (40 mg versus 10, p = 0.05). In vitro, the Fabs prevented enterococcal aggregation.


CONCLUSIONS
The 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.
Schlievert
Patrick M
PM
Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America. schli001@umn.edu
Chuang-Smith
Olivia N
ON
Peterson
Marnie L
ML
Cook
Laura C C
LC
Dunny
Gary M
GM
D000818:Animals; D004696:Endocarditis / Q000382:microbiology* / Q000503:physiopathology; D013293:Enterococcus faecalis / Q000302:isolation & purification*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D011817:Rabbits
D007140:Immunoglobulin Fab Fragments