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

Patrick M Schlievert; Olivia N Chuang-Smith; Marnie L Peterson; Laura C C Cook; Gary M Dunny

doi:10.1371/journal.pone.0013194

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

Journal article

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

Patrick M Schlievert, Olivia N Chuang-Smith, Marnie L Peterson, Laura C C Cook and Gary M Dunny

PloS one, Vol.5(10), p.e13194

10/04/2010

DOI: 10.1371/journal.pone.0013194

PMCID: PMC2949389

PMID: 20957231

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Abstract

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. 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. 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.

Enterococcus faecalis - isolation & purification

Rabbits

Animals

Endocarditis - microbiology

Immunoglobulin Fab Fragments - metabolism

Endocarditis - physiopathology

Details

Title: Subtitle: Enterococcus faecalis endocarditis severity in rabbits is reduced by IgG Fabs interfering with aggregation substance
Creators: Patrick M Schlievert - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America. schli001@umn.edu
Olivia N Chuang-Smith
Marnie L Peterson
Laura C C Cook
Gary M Dunny
Resource Type: Journal article
Publication Details: PloS one, Vol.5(10), p.e13194
DOI: 10.1371/journal.pone.0013194
PMID: 20957231
PMCID: PMC2949389
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: HL51987 / NHLBI NIH HHS R01 HL051987 / NHLBI NIH HHS
Language: English
Date published: 10/04/2010
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001202702771

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