MAPK/ERK signaling pathway in dictyostelium discoideum as a potential target for Escherichia coli TIR proteins 4445

Abstract Description Antimicrobial resistance represents a growing hazard to global public health, highlighting the need for novel therapeutics targeting specific bacterial defense mechanisms. Bacterial Toll/Interleukin-1 receptor (TIR) domain proteins aid bacterial survival by targeting host innate immune system signaling pathways and interfering with the immune response and represent a potential target for new therapies. To study the host immune signaling pathways modulated by bacterial TIR proteins, we are using the model organism Dictyostelium discoideum and uropathogenic Escherichia coli deficient for the bacterial TIR protein TcpC to determine if TcpC targets the MAPK/ERK signaling pathway in D. discoideum. Our methods include western blots and lawn assays to compare the responses of D. discoideum when exposed to bacteria with and without TcpC. The western blots suggest there are differences in Erk phosphorylation when D. discoideum is exposed to bacteria with and without TcpC, while the lawn assays show there does not appear to be differences in the ability of erkB-deficient D. discoideum to ingest bacteria with and without TcpC. These early results suggest that Erk may be a target of TcpC, and additional western blots and lawn assays will be performed to verify these findings. The characterization of bacterial Toll/Interleukin-1 receptor (TIR) domain proteins can inform the development of new therapies to combat antimicrobial resistance. Funding Sources Supported by NIH NIGMS T34GM150447 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)