1780-LB: Establishing a Mouse Model Resembling UTI Development in the Context of Type 2 Diabetes

Introduction and Objective: Urinary tract infections (UTIs) are more severe in patients with type 2 diabetes mellitus (T2DM) due to various factors such as glycosuria and impaired immune responses. However, the precise mechanisms by which uropathogens exploit these conditions to colonize the urinary tract remain inadequately understood, partly due to the absence of suitable animal models. This study aims to establish a mouse model that mimics UTI development in individuals with diet-induced T2DM (UTI-T2DM model). Methods: Diet-induced obese (DIO) male mice were fed special diets for 12, 16, and 20 weeks-high-fat diet (HFD, 60% fat) or low-fat diet (LFD, 10% fat). Subsequently, HFD and LFD mice were infected with uropathogenic E. coli (UPEC, 1x108 CFUs) via transurethral inoculation. Diabetes-like criteria were assessed through body weight, glucose levels, insulin levels, and oral glucose tolerance tests (OGTT). Bacterial burden was measured at 24- and 48-hours post-infection in collected bladders, prostates, ureters, and kidneys. The antimicrobial capacity of neutrophils isolated from infected HFD and LFD mice was evaluated. Differences between groups were analyzed using the t-test and Mann-Whitney U test, p-value is ≤0.05. Results: DIO-HFD mice present higher body weight, hyperglycemia and hyperinsulinemia at 12, 16 and 20 w.s.d. compared to LFD mice. DIO-HFD mice exhibited significantly more bacterial burden in the urinary tract compared to LFD mice at 20 w.s.d. The bactericidal capacity of neutrophils from DIO-HFD mice was significantly impaired compared to their LFD counterparts. Conclusions: DIO-HFD mice exhibit features resembling human T2DM and are significantly more susceptible to UTIs, making them a valuable model for investigating UTI susceptibility in the setting of diabetes. Disclosure Y.I. Sanchez-Zamora: None. J.M. Lopez-Torres: None. R. Li: None. A. Oliverio: None. I. Cotzomi-Ortega: None. G. Sanchez-Orellana: None. J. Ruiz-Rosado: None. Funding Research Institute at Nationwide Children's Hospital (AWD0000TBD), K01 NIH (DK128379).