Grant: CIHR Fellowship

Due to increasingly widespread antibiotic resistance, it is predicted that by 2050 bacterial infections will be causing more deaths than cancers. Bacterial pathogens subvert host processes by injecting protein virulence factors (effectors) into host cells to modify the behaviors of specific host proteins, thus causing disease. However, there has been limited success in elucidating effector roles and, correspondingly, pathogenesis mechanisms. This limits the development of new treatment strategies, which are becoming essential in view of increasingly widespread antimicrobial resistance. Salmonella enterica serovar Typhimurium (STm) is one of the best-studied and understood model bacterial pathogens. It causes different diseases in humans and mice. It has been the target of intense scientific investigations for decades. However, its pathogenesis mechanisms are still poorly understood and cellular targets have been identified or predicted for only about half of STm's 45 effectors. The proposed project will systematically identify host proteins interacting with each of the 45 effectors and map downstream changes to protein complexes, occurring as a result of the bacterial infection in human and mouse cells. The resulting data will be used to predict effector roles and to identify disease determinants that are associated with each type of disease and outcome. Successful implementation of the proposed project will represent a significant step forward in knowledge discovery about bacterial pathogenesis. In addition to making significant scientific discoveries, it will provide important resources and tools for future studies, thus speeding up future investigations and helping shape how bacterial pathogenesis mechanisms for a variety of pathogens are investigated in the future. In the long term, it will contribute to reducing healthcare costs and combatting the rise in antimicrobial resistance.