Obesity promotes urinary tract infection by disrupting bladder focal adhesion kinase signaling

Obesity is a significant public health concern associated with numerous health risks. Infections are a major complication of obesity, but the mechanisms driving increased infection risk remain unclear. Using a diet-induced obesity mouse model in male and female C57BL/6 mice, we show that high-fat diet feeding heightens vulnerability to uropathogenic E. coli (UPEC) urinary tract infection. Transcriptomic analysis of bladder urothelial cells revealed sex-specific gene expression changes with the shared activation of focal adhesion and extracellular matrix pathways. Western blotting and immunostaining confirmed focal adhesion kinase activation, a central component of the focal adhesion pathway, in the bladders of obese female and male mice. In primary human urothelial cells, focal adhesion kinase overexpression promoted UPEC invasion. These findings indicate that obesity enhances urinary tract infection susceptibility and identify focal adhesion kinase as a conserved pathway deregulated by obesity that contributes to increased UPEC vulnerability.