Burnette-Curley D, Wells V, Viscount H, Munro C L, Fenno J C, Fives-Taylor P, Macrina F L
Department of Microbiology and Immunology, Medical College of Virginia-Virginia Commonwealth University, Richmond 23298, USA.
Infect Immun. 1995 Dec;63(12):4669-74. doi: 10.1128/iai.63.12.4669-4674.1995.
Adherence of microorganisms to damaged heart tissue is a crucial event in the pathogenesis of infective endocarditis. In the present study, we investigated the role of the FimA protein as a potential virulence factor associated with Streptococcus parasanguis endocarditis. FimA is a 36-kDa surface protein that is a recognized adhesin in the oral cavity where it mediates adherence to the salivary pellicle. An insertion mutant and a deletion mutant of S. parasanguis were employed in the rat model of endocarditis to determine the relevance of FimA in endocarditis pathogenesis. Catheterized rats were infected with either the fimA deletion mutant VT929, the fimA insertion mutant VT930, or the isogenic, wild-type S. parasanguis FW213. Rats inoculated with FW213 developed endocarditis more frequently (50.9%) than animals inoculated with either the deletion mutant (2.7%) or the insertion mutant (7.6%) (P < 0.001). A series of in vitro assays were performed to explore the mechanism(s) by which FimA enhanced the infectivity of S. parasanguis. FimA did not inhibit the uptake or the subsequent killing of S. parasanguis by phagocytic granulocytes. Similarly, FimA did not play a role in the adherence to or the aggregation of platelets. Significant differences were noted between FW213 and VT929 (P < 0.05) and FW213 and VT930 (P < 0.001) in their abilities to bind to fibrin monolayers. The mean percent adherence of FW213 to fibrin monolayers (2.1%) was greater than those of VT929 (0.5%) and VT930 (0.12%). Taken together, these results indicate that FimA is a major virulence determinant associated with S. parasanguis endocarditis and further suggest that its role is associated with initial colonization of damaged heart tissue.
微生物对受损心脏组织的黏附是感染性心内膜炎发病机制中的关键事件。在本研究中，我们调查了FimA蛋白作为与副血链球菌心内膜炎相关的潜在毒力因子的作用。FimA是一种36 kDa的表面蛋白，是口腔中公认的黏附素，可介导与唾液薄膜的黏附。在大鼠心内膜炎模型中使用副血链球菌的插入突变体和缺失突变体来确定FimA在心内膜炎发病机制中的相关性。将导管插入大鼠体内，分别用fimA缺失突变体VT929、fimA插入突变体VT930或同基因野生型副血链球菌FW213进行感染。接种FW213的大鼠发生心内膜炎的频率（50.9%）高于接种缺失突变体（2.7%）或插入突变体（7.6%）的动物（P < 0.001）。进行了一系列体外试验以探究FimA增强副血链球菌感染性的机制。FimA不抑制吞噬性粒细胞对副血链球菌的摄取或随后的杀伤。同样，FimA在与血小板的黏附或聚集中不起作用。FW213与VT929（P < 0.05）以及FW213与VT930（P < 0.001）在结合纤维蛋白单层的能力上存在显著差异。FW213对纤维蛋白单层的平均黏附百分比（2.1%）高于VT929（0.5%）和VT930（0.12%）。综上所述，这些结果表明FimA是与副血链球菌心内膜炎相关的主要毒力决定因素，并进一步表明其作用与受损心脏组织的初始定植有关。
