Abstract 280: Thrombospondin-1 Carries CD55 like Domains: A Novel Target for E. coli Invasion into Human Heart Cells

Introduction: E. coli septicemia with cardiovascular dysfunction is among most frequent causes of human mortality however, underlying molecular mechanisms remain unknown. We recently described a fatal case of uro-sepsis with E. coli, bearing invasion-ligand Dr-adhesin, resulting in myocardial necrosis. Here we investigated an unrecognized mechanism of pathogen mediated cardiac cell invasion as a contributing factor to cardiovascular pathology and patient mortality. Methods: The experiments on human cardiac fibroblasts (HCF) showed E. coli colonization and invasion. However, the primary cell receptor for Dr adhesin, CD55, was undetectable. Searching for an alternative receptor we focused on matrix protein TSP-1 which is elevated in heart during infection. We over-expressed TSP1 in HCF cells (HCF-TSP1) and challenged with Dr+ E. coli. Bacterial binding/invasion to HCF-TSP1 and wild-type (WT) HCF were compared and evaluated. To rule out the possibility of fibroblast invasion due to presence of CD55 we perfor...