Exploring the effect of TcpC enzymatic activity on planarian clearance of Uropathogenic Escherichia coli 3432

Abstract Description Bacterial resistance is a threat to global health. Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections, and due to antibiotic treatment, there has been a notable rise in the levels of antibiotic-resistant bacteria. Studying this bacteria’s molecular mechanisms could provide insight into how to counteract the threat of bacterial resistance. UPECs produce a protein known as TcpC. TcpC is a Toll/interkeukin-1 receptor domain-containing protein (TIR) which acts as a virulence factor by inhibiting innate immune host immune responses. To study TcpC in E. coli we used the model organism planaria. Planaria are an emerging model for host- pathogen interactions due to their efficiency at clearing bacteria. Because TcpC blocks mammalian innate immune responses, we hypothesized that TcpC would also block planarian responses, and that when fed a variant of E. coli lacking TcpC, bacterial clearance will occur faster versus than when fed E. coli with TcpC. Results in our laboratory have supported this hypothesis. We now aim to explore aspects of the protein TcpC and effects it has on host immune response. First, we plan to test the role that TcpC enzymatic activity has on planarian immune response. In addition, we plan to study transcriptional responses of planaria to TcpC to identify specific genetic pathways that are affected by TcpC. Characterization of pathways targeted by TcpC in planarian may inform future areas for targeted therapeutics for UPECs Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)