Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
PLoS One. 2010 Oct 4;5(10):e13194. doi: 10.1371/journal.pone.0013194.
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 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/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.
粪肠球菌是感染性心内膜炎的重要病因，感染会导致心内膜内皮细胞形成赘生物（附着在心脏内皮组织下的微生物、纤维蛋白、血小板和宿主细胞）。我们之前的研究表明，肠球菌聚集物质（AS）是导致心内膜炎的重要毒力因子，尽管在没有 AS 产生的情况下也可能发生心内膜炎。粪肠球菌产生的 AS 通过 AS 与肠球菌结合物质结合，导致细菌形成聚集物。在这项研究中，我们评估了针对 AS 的 IgG 和 IgG Fab 对 AS+粪肠球菌心内膜炎的保护作用。
方法/主要发现：在 AS+粪肠球菌的攻击下，10 只主动免疫 AS+粪肠球菌的兔子比 9 只免疫 AS-粪肠球菌的兔子形成了更大的赘生物，且 9/10 只兔子死亡，而 9/9 只只兔子存活（p<0.005），这表明 IgG 的聚集作用显著促进了疾病的发生。体外试验表明，针对 AS 的 IgG 抗体也增强了肠球菌的聚集作用。相比之下，从主动免疫纯化 AS 的兔子中分离的 IgG Fab 片段，在被动给予兔子（每组 6 只）并立即用 AS+粪肠球菌攻击之前，可减少总赘生物（心内膜炎病变）微生物计数（7.9 x 10⁶ 对 2.0 x 10⁵，p=0.02）和大小（40 mg 对 10，p=0.05）。体外试验中，Fab 阻止了肠球菌的聚集。
结论/意义：这些数据证实了 AS 在感染性心内膜炎形成中的作用，并表明使用针对 AS 的 Fab 将提供部分保护，防止 AS+粪肠球菌感染。
