Dissecting bacterial interactions with the urothelium using emergent mass al spectrometry techniques (360G-Wellcome-099806_Z_12_Z)

Urinary tract infections (UTI) caused by uropathogenic E. coli (UPEC) cause significant levels of morbidity across a broad spectrum of clinical populations. The urothelium is recognised as an active tissue, with important roles in damage response and sensing within the bladder, including its role asthe primary effector of the immune response to UPEC infection. Previous work in the Southgate group has shown that diffusible mediators, such as ATP, play an important role in urothelial response to damage and healing. Evidence exists that extracellular ATP can also stimulate bacterial biofilm formation, offering protection against the immune response. The effects of UPEC-urothelial interaction and its respective effects on UPEC phenotype ad urothelial homeostasis are poorly understood. We aim to develop state of the art mass spectrometry techniques to enable the analysis of the intracellular metabolome and the extracellular secretome of normal human urothelial (NHU) cells in order to further understand the role that diffusible mediators play in the interaction between the urothelium, UPEC, and the urothelial response to damage and repair.