IRON AND PATHOGENESIS OF PORPHYROMONAS GINGIVALIS

人类和其他哺乳动物宿主有许多抑制生长的潜能

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.