Physiological in vitro models for studying infection and treatment of uropathogenic E. coli in the urogenital tract
Speaker: Christoph Dehio (University of Basel)
Host: Heike Brötz-Oesterhelt (IMIT)
Date & Time: 09.11.2023 | 12:30 – 2 p.m.
Venue: Lecture Hall 3M07, GUZ
Abstract:
Urinary tract infections (UTIs) are among the most common bacterial infections in humans and represent a major cause of human morbidity and mortality worldwide. The vast majority of UTIs are caused by uropathogenic Escherichia coli (UPEC). UTIs are the primary cause for the prescription of antibiotics and thus represent a major driver of antimicrobial resistance evolution. Moreover, following standard-of-care antibiotic treatment, up to 50% of patients experience recurrent infection, necessitating further treatment. The bacterial and host factors that contribute to UTI and the response to drug treatment remain poorly understood, which in part is due to the lack of physiological models for studying UTI in vitro.
I will present our ongoing efforts to establish models and tools for studying UPEC infection and treatment under patient-like conditions, including a well characterized collection of clinical UPEC isolates, a synthetic human urine model for axenic studies, and a human urothelial barrier model in a microphysiological set-up for studying UPEC infection and treatment at the tissue level. We are using proteomic and transcriptomic analysis for benchmarking these models against human UTI samples, and genome-wide CRISPRi for mapping fitness landscapes in these physiological in vitro models.