Canine urothelial cell model to study intracellular bacterial community development by uropathogenic Escherichia coli

Urinary tract infections (UTIs) are among the most common bacterial infections of both dogs and humans, with most caused by uropathogenic Escherichia coli (UPEC). Recurrent UPEC infections are a major concern in the treatment and management of UTIs in both species. In humans, the ability of UPECs to form intracellular bacterial communities (IBCs) within urothelial cells has been implicated in recurrent UTIs. However, the role of IBCs has not been explored in the pathogenesis of canine recurrent UTIs. In this study, we identified IBCs in both urine and bladder tissue from dogs with UPEC associated UTIs. In addition, we showed that UPECs derived from canine UTIs form IBCs within primary canine urothelial cells. As in human UTIs, formation of IBCs by canine UPECs correlated with the presence of the fimH gene as those isolates lacking the fimH gene formed fewer IBCs in canine urothelial cells then those harboring the fimH gene. Additionally, UPEC strains from clinical cases classified as recurrent UTIs had higher rates of IBC formation than UPEC strains from non-recurrent UTIs. These IBCs were tolerant to treatment with enrofloxacin, cefpodoxime and doxycycline at 150, 50 and 50 μg/mL respectively, which are representative of the concentrations achieved in canine urine after standard dosing. This is consistent with the clinical perspective that current UTIs are a common condition of dogs and are difficult to manage through antimicrobial treatment. Additionally, the dog could prove to be a powerful model of IBC formation as they are natural models of UPEC-causing UTIs and have similar pathophysiology of IBC formation.