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The objective of the proposed research is to understand the mechanisms of iron acquisition by Neisseria meningitidis. We will be examining the role of iron-repressible outer membrane proteins in this process, using both classical and molecular genetic approaches. We will attempt to resolve the existing controversy as to whether the meningococcus produces a hydroxamate siderophore, and will examine the possibility that a putative siderophore may be produced in response to environmental cues other than iron-limitation. Since transferrin and lactoferrin are available in vivo at sites where the meningococcus resides, we expect that the study of these two iron sources in vitro is biologically relevant. The biological relevance of hemin and hemoglobin utilization is unclear at present; all assays done to date have used these iron carriers in their free form, while in the body they probably exist bound to carrier proteins (hemopexin and haptoglobin). Thus, we intend to assess how these carrier proteins affect the utilization of hemin and hemoglobin. These studies are important in furthering our understanding of a novel iron uptake system. These studies will provide an important basis for future studies on the relationship of meningococcal iron acquisition and virulence. Ultimately, this knowledge may be of use in the development of novel meningococcal vaccines directed against the meningococcal iron uptake system.
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