A catheter-associated urinary tract infection mouse model to study bladder dysfunction and pain

Bladder pain and dysfunction are common symptoms in patients with urinary tract infections (UTIs), including catheter-associated UTIs (CAUTIs). Underlying mechanisms of chronic bladder pain and recurrent UTIs remain poorly understood, and good translational mice models are sparse. Here, we developed a female mouse suprapubic CAUTI model, and combined in vivo and ex vivo imaging techniques and behavioral assays to longitudinally evaluate the consequences for bladder function, inflammation, abdominal pain, bacterial colonization, and biofilm. Catheter-associated urinary tract infection animals, with an implanted suprapubic bladder catheter infected with the bioluminescent uropathogenic Escherichia coli (UPEC) UTI89-Lux strain, were compared with sham-operated mice (SHAM), mice with a sterile catheter (CACON), and mice infected via transurethral instillation (UTI). Compared to transient infections in UTI mice, CAUTI mice exhibited sustained bacterial infection during >2 weeks, which was associated with bacterial biofilm formation on the catheter inner surface. Compared to CACON mice, CAUTI mice showed a more pronounced increase in suprapubic sensitivity, which was sensitive to antibiotic treatment. Void spot assays and fluoroscopic volumetry further revealed a smaller bladder capacity in both CAUTI and CACON mice, but only in CAUTI mice this was associated with reduced voiding efficiency. This model successfully recapitulates clinically relevant symptoms of CAUTI in patients and demonstrates that sustained bacterial colonization of the catheter directly contributes to bladder hypersensitivity and voiding dysfunction. This novel in vivo research model may be instrumental in the search for new therapies aimed at disrupting biofilms and treatments of bladder-related pain, infections, and dysfunction.