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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.

Enterococcus faecalis Subverts and Invades the Host Urothelium in Patients with Chronic Urinary Tract Infection