IRON AND PATHOGENESIS OF PORPHYROMONAS GINGIVALIS

人类和其他哺乳动物的宿主抑制了许多潜在的生长 病原体通过复杂的机制，称为营养免疫，阻止 从这些生物体中提取的必需铁。营养免疫控制着微生物 抑制增殖，从而使其他机制(专业吞噬细胞， 补体固定抗体)可以控制潜在的感染。病原体 有铁运输系统来克服这种宿主诱导的铁 剥夺，允许宿主组织、体液或其他组织无节制地生长 粘膜表面。因此，专门的表面暴露部件 细菌铁运输系统是有吸引力的目标 免疫预防。这些表面成分通常是保守的 针对这些铁摄取决定因素的抗原和抗体 通常会阻碍铁的吸收。这允许宿主重新获得对 通过重新发挥营养免疫来入侵微生物。我们的假设是 针对一个或多个铁运输系统的免疫预防 会阻止或减少与牙周病相关的牙周病 这种黑色素口腔厌氧菌。为了检验这一假设，我们将 产生牙龈假单胞菌的突变体，这种突变体的能力被阻止 运输血红素和亚铁。我们将克隆必需的基因 这些铁运输系统的外膜组件。这些基因 将在大肠杆菌中过度表达，牙龈假单胞菌的铁运输 OMPS将被提纯。然后我们将研究铁运输的行为 两种牙龈假单胞菌感染性模型中的突变体。我们还将确定 是否用纯化的外膜成分免疫动物 铁转运系统诱导对牙周炎杆菌的保护性免疫。

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.