COORDIANTION CHEMISTRY OF MICROBIAL IRON TRANSPORT

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DESCRIPTION: Iron is an essential growth element, but the availability of iron in an oxidizing environment is severely limited by the insolubility of Fe(OH)3. Microbes respond to this limitation by synthesizing low-molecular-weight chelating agents, siderophores, for which there are membrane-bound receptors. Often bacteria synthesize several siderophores and/or express multiple receptors. There is a clear link between iron and microbial virulence. Pathogenicity increases of up to 107 have been observed when the bacteriostatic effects of human iron complexing proteins are overcome. Previous studies have focussed on the structures of siderophores and the relationship of stereochemistry to siderophore mediated iron transport. Future work will address the dynamics of siderophore complexation in addition to the identification of new siderophores and their structure/function relationships. Fluorescent probes will be attached to siderophores to monitor both the spatial and temporal uptake of iron mediated by siderophores. The kinetics of ligand exchange and complex isomerization in catechol siderophores will be studied by NMR, and competition experiments will be used to obtain full thermodynamic characterization of siderophores. The overall focus of this research continues to be the coordination chemistry of siderophores, the connection of this chemistry to their biological activity, and the consequent medical significance of the results.