BIOLOGY OF INTRACELLULAR PARASITISM

对贝氏柯克斯体感染的发病机制进行了研究， 兔子和体外。 我们研究了（a） 实验性心内膜炎，（B）人血清补体的作用 对脂多糖（LPS）相变体的作用和（c）LPS的作用 相位变化。 A. 心内膜炎。 C.急性Q热的贝氏菌株和 心内膜炎患者的LPS结构不同， 让动物发烧 使用兔模型的研究 心内膜炎显示没有差异的能力， 九里毒株（典型的急性Q热毒株）和 Priscilla菌株（典型的心内膜炎菌株）定植 导管引起的心脏赘生物 体外试验显示， 这些菌株之间的差异在于它们粘附 纤维蛋白血小板凝块 B。 血清补体敏感性。 粗糙LPS相位变体 对血清敏感，而平滑期和中间期 变种人有抵抗力 平稳过渡期 然而，变异体在与 补体系统，这表明，他们的机制， 抵抗补体杀伤的能力不同。 C. LPS在相位变化中的作用。 天然相上的光滑LPS I变体在空间上阻断了抗体与表面的结合， 与II期细胞共有的蛋白质。 尽管这些 表面暴露的蛋白质，这些蛋白质可以被抗体接近， 因此，II期细胞可赋予表观II期细胞 血清特异性，这些研究表明， 决定因素是在第二阶段LPS。 这个项目的意义在于定义主机防御 控制C.贝氏体感染，在确定 某些菌株是否有引起心内膜炎的倾向， 以及开发有效的C.贝氏 心内膜炎

The pathogenesis of Coxiella burnetii infections was studied in rabbits and in vitro. We studied (a) the pathogenesis of experimental endocarditis, (b) the effect of human serum complement on lipopolysaccharide (LPS) phase variants and (c) the role of LPS in phase variation. A. Endocarditis. C. burnetii strains from acute Q fever and from endocarditis patients differ in LPS structure and in their ability to induce fever in animals. Studies using a rabbit model of endocarditis showed no differences between the abilities of the Nine Mile strain (typical of acute Q fever strains) and the Priscilla strain (typical of endocarditis strains) to colonize catheter-induced cardiac vegetations. An in vitro assay showed no differences between these strains in their abilities to adhere to fibrin-platelet clots. B. Serum complement-susceptibility. The rough LPS phase variant was serum sensitive, whereas the smooth and intermediate LPS phase variants were resistant. The smooth and intermediate phase variants, however, differed in their interactions with the complement system, suggesting that the mechanisms by which they resisted complement-killing were different. C. Role of LPS in phase variation. The smooth LPS on native phase I variants sterically blocked the binding of antibodies to surface proteins shared with phase II cells. Although any of these surface-exposed proteins which are accessible to antibodies on phase II cells may therefore confer apparent phase II serospecificity, these studies suggest that the unique phase determinant is in the phase II LPS. The significance of this project lies in defining host defence mechanisms controlling C. burnetii infections, in determining whether certain strains have a predilection to cause endocarditis, and in developing effective antimicrobial therapy for C. burnetii endocarditis.