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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 aggreg...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949389/ https://www.ncbi.nlm.nih.gov/pubmed/20957231 http://dx.doi.org/10.1371/journal.pone.0013194 |
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author | Schlievert, Patrick M. Chuang-Smith, Olivia N. Peterson, Marnie L. Cook, Laura C. C. Dunny, Gary M. |
author_facet | Schlievert, Patrick M. Chuang-Smith, Olivia N. Peterson, Marnie L. Cook, Laura C. C. Dunny, Gary M. |
author_sort | Schlievert, Patrick M. |
collection | PubMed |
description | 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 FINDINGS: 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 (7.9×10(6) versus 2.0×10(5), p = 0.02) and size (40 mg versus 10, p = 0.05). In vitro, the Fabs prevented enterococcal aggregation. CONCLUSIONS/SIGNIFICANCE: 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. |
format | Text |
id | pubmed-2949389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29493892010-10-18 Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance Schlievert, Patrick M. Chuang-Smith, Olivia N. Peterson, Marnie L. Cook, Laura C. C. Dunny, Gary M. PLoS One Research Article 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 FINDINGS: 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 (7.9×10(6) versus 2.0×10(5), p = 0.02) and size (40 mg versus 10, p = 0.05). In vitro, the Fabs prevented enterococcal aggregation. CONCLUSIONS/SIGNIFICANCE: 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. Public Library of Science 2010-10-04 /pmc/articles/PMC2949389/ /pubmed/20957231 http://dx.doi.org/10.1371/journal.pone.0013194 Text en Schlievert et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Schlievert, Patrick M. Chuang-Smith, Olivia N. Peterson, Marnie L. Cook, Laura C. C. Dunny, Gary M. Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
title |
Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
title_full |
Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
title_fullStr |
Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
title_full_unstemmed |
Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
title_short |
Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance |
title_sort | enterococcus faecalis endocarditis severity in rabbits is reduced by igg fabs interfering with aggregation substance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949389/ https://www.ncbi.nlm.nih.gov/pubmed/20957231 http://dx.doi.org/10.1371/journal.pone.0013194 |
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