We also focus on a complication of UTIs, namely, their propensity to recur frequently in a subset of patient population. Clinically, these recurrent UTIs and de novo acute infections are both thought to be due to re-contamination of the urinary tract from the intestinal reservoir. We showed that UPEC establish quiescent reservoirs in endosomal vesicles within the urinary bladder epithelium. UPEC residing within these membrane-bound vesicles can serve as a seed for a new infection concomitant with activation of a round of differentiation in the urothelium. We have recently demonstrated a role for autophagy in formation and maintenance of these latent infections.
We have shown that autophagy protein deficiency is associated with urothelial architectural defects and loss of the niche sought after by UPEC to persist. We are investigating these mechanisms further.