Exploring the Impact of Escherichia coli TcpC, a Bacterial TIR Domain-Containing Protein, Using Planaria and Dictyostelium discoideum as Model Organisms.

Abstract An estimated 1.2 million individuals lose their lives each year due to antibiotic-resistant bacterial infections, surpassing the mortality caused by HIV/AIDS or malaria. Uropathogenic Escherichia coli (UPEC) is among the most common causative agents of urinary tract infections (UTIs). UPECs survive in hosts using various mechanisms, including by secreting a protein known as TcpC. TcpC is a Toll-like/interleukin-1 receptor (TIR) domain-containing protein that modifies mammalian innate immunity by inhibiting the host Toll-like receptor (TLR) response. We hypothesize that TcpC also affects the survival of UPECs in model systems, including the social amoeba Dictyostelium discoideum and planaria flatworms. To test this hypothesis, we are using mutant strains of the UPEC CFTO73 that have altered expression of TcpC to analyze the effects of TcpC on bacterial growth and virulence in these model organisms. Our initial tests with D. discoideum indicate that the presence of TcpC in UPEC strains may increase their resistance to grazing and phagocytosis by the social amoeba D. discoideum. We are currently testing the effects of TcpC on survival of UPEC strains in planaria. If TcpC affects survival of UPECs in these model systems, this may open new avenues for characterization of the molecular mechanisms used by bacterial TIR domains to evade mammalian innate immune cells.