title: Forced resurgence and targeting of intracellular uropathogenic Escherichia coli reservoirs.
abstract: Intracellular quiescent reservoirs of uropathogenic Escherichia coli (UPEC), which can seed the bladder mucosa during the acute phase of a urinary tract infection (UTI), are protected from antibiotic treatments and are extremely difficult to eliminate. These reservoirs are a potential source for recurrent UTIs that affect millions annually. Here, using murine infection models and the bladder cell exfoliant chitosan, we demonstrate that intracellular UPEC populations shift within the stratified layers of the urothelium during the course of a UTI. Following invasion of the terminally differentiated superficial layer of epithelial cells that line the bladder lumen, UPEC can multiply and disseminate, eventually establishing reservoirs within underlying immature host cells. If given access, UPEC can invade the superficial and immature bladder cells equally well. As infected immature host cells differentiate and migrate towards the apical surface of the bladder, UPEC can reinitiate growth and discharge into the bladder lumen. By inducing the exfoliation of the superficial layers of the urothelium, chitosan stimulates rapid regenerative processes and the reactivation and efflux of quiescent intracellular UPEC reservoirs. When combined with antibiotics, chitosan treatment significantly reduces bacterial loads within the bladder and may therefore be of therapeutic value to individuals with chronic, recurrent UTIs.
authors.affiliation: Division of Microbiology and Immunology, Pathology Department, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Blango
authors.affiliation: Division of Microbiology and Immunology, Pathology Department, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Ott
authors.affiliation: Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljublijana, Slovenia.
authors.forename: Andreja
authors.initials: A
authors.lastname: Erman
authors.affiliation: Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljublijana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Veranic
authors.affiliation: Division of Microbiology and Immunology, Pathology Department, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Mulvey
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology*; D051379:Mice; D009092:Mucous Membrane / Q000166:cytology / Q000382:microbiology; D013997:Time Factors; D001743:Urinary Bladder / Q000166:cytology / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000502:physiology*