Placing the T3SS effector-network paradigm within a systems level understanding of in vivo infection

Bacterial gut infections are still a leading cause of morbidity and mortality. Many gut pathogens use a molecular syringe to inject bacterial proteins called effectors into human gut cells, where they highjack cellular processes for the benefit of the pathogen. We have recently shown, using the intestinal mouse pathogen Citrobacter rodentium as a model, that rather than functioning individually, the effectors form networks inside the infected cells. These networks allow for alternative connections to be formed when specific effectors are absent, making effectors a very robust virulence mechanism. The overarching aim of this proposed research is to explore the "effector network" paradigm. We will study how the effector networks impact disease progression, how their signals are transmitted from epithelial to immune cells and how the host genetic background and age affect these networks. Finally, we will use the data to train our AI model to better predict infection outcomes.