Iron acquisition in Streptococcus pyogenes

Georgia State University, Atlanta GA

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Abstract

DESCRIPTION (provided by applicant): Streptococcus pyogenes is an important human pathogen that causes mild to aggressive life threatening infections. An unexplained increase in the frequency and severity of streptococcal infections has been observed since the 1980s. The hemolytic S. pyogenes can use several heme-proteins to support its growth in irondepleted media, suggesting that hemoproteins are an important iron source for streptococcus during infection. Two streptococcal transporters with homology to transporters of iron-complexes have been identified. We hypothesize that both systems are involved in iron acquisition from hemoproteins during infection. Our goal is to elucidate the mechanisms of iron uptake by S. pyogenes. The first specific aim characterizes the functional role of both streptococcal loci. The second aim investigates the structure and functional interaction of the proteins that compose one of the systems. Mutants will be constructed and analyzed for their ability to utilize different hemoproteins, employing binding and transport assays. Protein interactions will be studied by immunoprecipitation, cross-linking and solid-phase binding assays. This study will enhance our knowledge of the interaction between S. pyogenes and its human host and may identify new targets for therapeutic intervention.