Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Frontiers in Cellular and Infection Microbiology

Jennifer L. Rohn¹  Carlos Flores¹  Karolina M. Kwiatkowska¹  Benjamin O. Murray¹  Elizabeth E. Marr²  Joseph L. Charest²  Corin Williams²  Deborah A. Flusberg²  Brett C. Isenberg² 

[1] Centre for Urological Biology, Department of Renal Medicine, University College London, London, United Kingdom;Department of Bioengineering, Charles Stark Draper Laboratory, Inc., Cambridge, MA, United States;

关键词: urinary tract infection (UTI);    microphysiological systems;    in vitro;    organ-on-chip;    organoid;    urothelium;    E. coli;    mouse models;   

DOI  :  10.3389/fcimb.2021.691210

来源: Frontiers

【 摘 要 】

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.

【 授权许可】

CC BY