title: Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection.
abstract: Bacterial urinary tract infections (UTI) are a major growing concern worldwide. Uropathogenic Escherichia coli has been shown to invade the urothelium during acute UTI in mice and humans, forming intracellular reservoirs that can evade antibiotics and the immune response, allowing recurrence at a later date. Other bacterial species, such as Staphylococcus saprophyticus, Klebsiella pneumonia and Salmonella enterica have also been shown to be invasive in acute UTI. However, the role of intracellular infection in chronic UTI causing more subtle lower urinary tract symptoms (LUTS), a particular problem in the elderly population, is poorly understood. Moreover, the species of bacteria involved remains largely unknown. A previous study of a large cohort of non-acute LUTS patients found that Enterococcus faecalis was frequently found in urine specimens. E. faecalis accounts for a significant proportion of chronic bladder infections worldwide, although the invasive lifestyle of this uropathogen has yet to be reported. Here, we wanted to explore this question in more detail. We harvested urothelial cells shed in response to inflammation and, using advanced imaging techniques, inspected them for signs of bacterial pathology and invasion. We found strong evidence of intracellular E. faecalis harboured within urothelial cells shed from the bladder of LUTS patients. Furthermore, using a culture model system, these patient-isolated strains of E. faecalis were able to invade a transitional carcinoma cell line. In contrast, we found no evidence of cellular invasion by E. coli in the patient cells or the culture model system. Our data show that E. faecalis is highly competent to invade in this context; therefore, these results have implications for both the diagnosis and treatment of chronic LUTS.
authors.affiliation: Centre for Clinical Science and Technology, Research Department of Clinical Physiology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: Harry
authors.initials: H
authors.lastname: Horsley
authors.affiliation: Centre for Clinical Science and Technology, Research Department of Clinical Physiology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Malone-Lee
authors.affiliation: Centre for Clinical Science and Technology, Research Department of Clinical Physiology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Holland
authors.affiliation: Centre for Clinical Science and Technology, Research Department of Clinical Physiology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Tuz
authors.affiliation: Imaging Suite, Royal Veterinary College, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hibbert
authors.affiliation: Department of Microbiology, The Whittington Hospital NHS Trust, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Kelsey
authors.affiliation: Centre for Clinical Science and Technology, Research Department of Clinical Physiology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kupelian
authors.affiliation: Centre for Clinical Science and Technology, Research Department of Clinical Physiology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rohn
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002908:Chronic Disease; D013293:Enterococcus faecalis / Q000502:physiology*; D006801:Humans; D008131:London; D008856:Microscopy, Fluorescence; D001743:Urinary Bladder / Q000166:cytology; D014552:Urinary Tract Infections / Q000382:microbiology* / Q000503:physiopathology*; D019459:Urothelium / Q000382:microbiology* / Q000503:physiopathology