A simple ex vivo bladder infection model permits study of host-pathogen interactions in urinary tract infection

Abstract Urinary tract infections (UTI) are very common infections. To study UTI, researchers often use animal models, but studying certain phenotypes is difficult and comes with ethical and administrative challenges. To address these challenges, we developed a reproducible and cost-effective model to study UTI using donated mouse bladders that would otherwise be discarded. This model, which is easily mastered, supports study of interactions between the host and bacteria in a controlled environment. We found that uropathogenic E. coli colonization and invasion in our model was comparable to in vivo mouse models. To optimize reproducibility, we tested variables including incubator conditions, and biological factors like donor mouse sex or pregnancy. Our method allows assessment of early host-pathogen interactions, immune cell uptake, the impact of age and sex, and diverse bacterial strains or treatments. In some countries, sharing material from animals sacrificed for other reasons does not require additional ethical approval, providing a resource for labs without animal access and reducing administrative burden. Given the breadth of the model to test sex, age, mouse and bacterial strain, or any parameter that can be adapted to a 96-well plate, this model has potential application beyond infection or even beyond the bladder to other tissues.