Unravelling the factors that shape the intracellular lifecycle of uropathogenic Escherichia coli

Introduction Uropathogenic Escherichia coli (UPEC) cause the majority of uncomplicated urinary tract infections (UTIs), an increasing global disease burden prevalent among women. UPEC invasion of the bladder epithelium and development of intracellular bacterial communities (IBCs) contribute to the establishment, persistence and recurrence of UTIs. The intracellular localization renders UPEC resistant to antibiotic treatment and host clearance, leading to bacterial persistence and subsequent recurrent UTI.

Goals Our understanding of regulatory steps leading to the different stages of IBC formation and the interaction between bacterial and host cell factors during the intracellular lifecycle remains incomplete. We aim to uncover mechanistic relationships underlying recurrent UTIs by deepening the understanding of UPEC-urothelial cell interplay.

Materials & Methods We analyzed the intracellular life cycle of different clinical UPEC isolates in the human epithelial urinary bladder carcinoma cell line RT-112. We quantified the invasion rate, intracellular survival and exit behavior, and monitored the development and formation of IBCs using fluorescence microscopy.

Results Our infection protocol allows us to track the intracellular life cycle of UPEC. We show that individual UPEC isolates differ in their invasion rate, intracellular replication/survival, exit efficiency as well as in the morphology of their intracellular communities. Furthermore, the functionality of the endosomal compartment and intracellular transport affect the intracellular life cycle of UPEC.

Summary Our results show that UPEC isolates differ in certain aspects of the intracellular lifecycle. This could also affect the ability of UPEC isolates to persist in the urinary tract and cause recurrent urinary tract infections.