Mimicking Urinary Tract Infections Caused by Uropathogenic Escherichia coli Using a Human Three-Dimensional Tissue Engineering Model

Abstract

Uropathogenic Escherichia coli are the main causal agent of urinary tract infections. These diseases can affect more than half of women during their lifetime. Moreover, recurrent urinary tract infections can affect up to 30% of patients, leading to higher social and economic costs for the community. No efficient treatment against the recurrent form of the disease has been discovered. Due to the low average rate of successful translation from 2D cell culture and in vivo animal models into clinical trials, new models that mimic pathologies, such as those produced by tissue engineering, are needed. A model of human-derived 3D bladder mucosa was produced by tissue engineering techniques using collagen gels and organ-specific primary human stromal and epithelial cell populations. This model was used to mimic the different steps of a urinary tract infection: adhesion, invasion, intracellular bacterial community and quiescent intracellular reservoir formation and, finally, bacteria resurgence after umbrella cell exfoliation through chitosan exposure to mimic the recurrent infection. The uropathogenic strain UTI-89-GFP was used as infectious bacteria and BL-21-GFP strain as a control. Our model is unique and is the first step toward mimicking the different phases of a UTI in a human context.