Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and a leading cause of antibiotic use in primary care. Current treatments rely heavily on antibiotics, which contribute to antimicrobial resistance and often fail to prevent recurrent infections. Despite efforts to develop alternative therapies, options remain limited due to gaps in our understanding of these infections. To address this challenge, the Aguilar Lab develops advanced in vitro models of the bladder and prostate using adult stem cell–derived organoids. These models closely mimic the epithelial compartment of the urinary tract and enable investigation of the host response to infection in a physiologically relevant setting. By combining organoid systems with technologies such as single-cell RNA sequencing and CRISPR-based editing, we aim to identify host factors that influence infection outcomes and support bacterial persistence. In this talk, I will present how the development of a prostate organoid model led us to uncover a mechanism by which UPEC uses the FimH adhesin to invade differentiated luminal cells via a specific glycosylated host receptor. Targeting this interaction significantly reduces bacterial invasion, offering a promising host-directed strategy for managing bacterial prostatitis.