Grant: Operating Grant

Iron is growth essential for almost all human pathogens and thus bacterial iron acquisition systems are recognized generally as virulence factors. This proposal focuses on investigation of the mechanisms employed by a key iron transport system in a clinically important human pathogen Staphylococcus aureus that cause debilitating and life threatening infections. The rapid spread of methicillin resistant S. aureus (MSRA, a.k.a. the superbug) in both community and hospital settings, has accelerated the need for understanding this pathogen's virulence repertoire for the development of new therapeutic approaches. Staphyloferrin A and staphyloferrin B siderophores are low molecular weight iron chelators that are used by S. aureus to scavenge iron. These iron transport systems have components shown to be required for optimal growth under iron limitation and for colonization or pathogenesis in model animal systems. We will make use of the complementary strengths from our two labs to drive a concerted approach to understand the mechanisms of key steps in staphyloferrin A and B synthesis and uptake. Specifically, we will crystallography to determine high resolution structures of the enzymes and receptors to gain insight into their function. Assays will be used to test hypotheses concerning specificity of these proteins.