IRON AND PATHOGENESIS OF PORPHYROMONAS GINGIVALIS

人类和其他哺乳动物宿主抑制了许多潜在的 病原体通过复杂的机制，称为营养免疫， 这些有机体中的铁元素 营养免疫保持微生物 抑制增殖以使其它机制（专职吞噬细胞， 补体结合抗体）可以控制潜在的感染。 病原体 有铁运输系统，克服这种主机诱导铁 剥夺，允许在宿主组织、体液或其他组织中不受限制地生长。 粘膜表面。 因此，表面暴露的组件的专门 细菌铁转运系统是 免疫预防。 这些表面成分通常是保守的 抗原和针对这些铁吸收决定簇的抗体 常常阻碍铁的吸收。 这允许宿主重新获得对 通过重新发挥营养免疫力， 我们的假设是 针对一种或多种铁转运系统的免疫预防 的牙龈卟啉单胞菌将阻止或减少牙周病相关的 这种黑色口腔厌氧生物。 为了验证这个假设，我们将 产生牙龈卟啉单胞菌的突变体， 运输血红素和亚铁。 我们将克隆基因， 这些铁运输系统的外膜组件。 这些基因 在E.大肠杆菌和牙龈卟啉单胞菌铁转运 OMP将被纯化。 然后，我们将研究铁运输的行为， 牙龈卟啉单胞菌感染性的两种模型中的突变体。 我们还将确定 是否用纯化的外膜成分免疫动物 铁转运系统诱导针对牙龈卟啉单胞菌的保护性免疫。

Man and other mammalian hosts suppress the growth of many potential pathogens by complex mechanisms, termed nutritional immunity, that withhold essential iron from these organisms. Nutritional immunity holds microbial proliferation in check so that other mechanisms (professional phagocytes, complement-fixing antibodies) can control a potential infection. Pathogens have iron transport systems that overcome this host-induced iron deprivation, allowing unchecked growth in host tissues, body fluids or on mucosal surfaces. Thus, surface-exposed components of specialized bacterial iron transport systems are attractive targets for immunoprophylaxis. These surface components are commonly conserved antigens, and antibodies directed against these iron uptake determinants often block iron uptake. This allows the host to regain control of an invading microbe by re-exerting nutritional immunity. Our hypothesis is that immunoprophylaxis directed against one or more iron transport systems of P. gingivalis will block or diminish periodontal disease associated with this black-pigmented oral anaerobe. To test this hypothesis, we will generate mutants of P. gingivalis that are blocked in the ability to transport heme and ferrous iron. We will clone the genes for essential outer membrane components of these iron transport systems. These genes will be over-expressed in E. coli, and the P. gingivalis iron transport OMPs will be purified. We will then examine the behavior of iron transport mutants in two models of P. gingivalis infectivity. We will also determine whether immunization of animals with purified outer membrane components of the iron transport system induce protective immunity against P. gingivalis.