Examination of Staphylococcus aureus interactions with hemoglobin

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DESCRIPTION (provided by applicant): The principal investigator, (Dr. Boles), is currently a postdoctoral fellow at the University of Iowa. He has significant experience studying bacterial physiology and biofilm development in multiple pathogenic bacterial species. Within the next 12 months, he plans on obtaining a tenure track academic position at a major research institute with a future research focus on understanding S. aureus physiology and pathogenesis. The long-term objectives of his laboratory will be to understand the molecular mechanisms involved in S. aureus iron acquisition from mammalian host proteins and how these host proteins influence biofilm formation and dispersal. The proposed research will focus on elucidating how S. aureus obtains heme (and therefore iron) from hemoglobin and examining how hemoglobin influences S. aureus gene expression and biofilm development. Preliminary work has uncovered that S. aureus extracellular protease activity is necessary for iron acquisition from hemoglobin and hemoglobin can influence the production of S. aureus proteases. The specific aims of this proposal are designed to 1) identify the specific S. aureus extracellular protease(s) necessary for heme acquisition from hemoglobin, 2) define the regulatory effects of hemoglobin on extracellular protease expression, and 3) examine the influence of hemoglobin on S. aureus biofilm formation. Dr. Boles' research plan has great relevance to public health as S. aureus is a major cause of infection and death in community and hospital associated infections. Findings from the proposed project will increase understanding of S. aureus pathogenic mechanisms and may lead to new therapeutic options for treating S. aureus infections.