IRON AND PATHOGENESIS OF PORPHYROMONAS GINGIVALIS

铁与牙龈卟啉单胞菌的发病机制

• 批准号: 3753723
• 负责人: DAVID DYER
• 金额: --
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3753723
• 关键词: Bacteroides gingivalis; affinity chromatography; bacterial antigens; biological transport; cell membrane; chimeric proteins; disease /disorder model; heme; immunization; ion transport; iron; laboratory mouse; laboratory rat; molecular cloning; mutant; pathologic process; periodontium disorder; porphyrins; protein purification; site directed mutagenesis; virulence

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.

人和其他哺乳动物宿主抑制了许多潜力的增长 通过复杂机制的病原体，称为营养免疫，扣留 这些生物的基本铁。 营养免疫可容纳微生物 检查中的扩散，以使其他机制（专业的吞噬细胞， 补体固定抗体）可以控制潜在的感染。 病原体 具有克服该宿主引起的铁的铁运输系统 剥夺，允许宿主组织，体液或上方不受限制的生长 粘膜表面。 因此，专业的表面暴露成分 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 抗原和针对这些铁摄取决定因素的抗体 通常阻止铁吸收。 这使主机可以重新控制 通过重新履行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 牙龈疟原虫会阻塞或减少与 这种黑色的口腔厌食症。 为了检验这一假设，我们将 产生牙龈疟原虫的突变体，这些突变体被阻止 运输血红素和铁铁。 我们将克隆基因的必要 这些铁运输系统的外膜组件。 这些基因 将在大肠杆菌和牙龈疟原虫铁中过表达 OMP将被纯化。 然后，我们将检查铁运输的行为 两种模型的牙龈疟原虫感染性模型中的突变体。 我们还将确定 是否具有纯化的外膜成分的动物免疫 铁运输系统诱导牙龈疟原虫的保护性免疫。