Analyzing TcpC-mediated modulation of D. discoideum signaling pathways in Uropathogenic Escherichia coli 3851

Abstract Description Uropathogenic Escherichia coli (UPEC), a pathogenic bacterium that causes urinary tract infections (UTIs), produces a virulence factor called TcpC. TcpC is a secreted toll/interleukin-1 receptor protein domain, which is significant because mammalian cells also contain TIR domain-containing proteins. This similarity allows TcpC to disrupt mammalian signaling pathways, aiding in UPEC evasion of the host immune system. Dictyostelium discoideum (D. discoideum), a soil dwelling amoeba, serves as an essential model organism due to its conserved functions and parallels to mammalian host-pathogen interactions. We hypothesize that TcpC inhibits D. discoideum signaling pathways. To test this hypothesis, we are performing grazing resistance assays and qRT-PCR to (1) characterize interactions between TcpC-expressing bacteria and D. discoideum strains with gene deficiencies, and (2) compare phagocytosis gene expression in D. discoideum in the presence or absence of TcpC. Preliminary results suggest that D. discoideum grazes more efficiently on TcpC-deficient E. coli strains, suggesting TcpC plays a role in inhibiting D. discoideum grazing efficiency. Currently, we are exploring the effects of TcpC on D. discoideum signaling pathways, including investigating TcpC’s enzymatic activity and its potential to disrupt these pathways. Understanding these mechanisms may allow for development of therapeutics for UTIs. Funding Sources NIH #1T32GM146694-01 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)