Single nucleus transcriptomics to study sex differences during murine E. coli pyelonephritis

This project employs models of urinary tract infection (UTI) in female, androgen-exposed female, and male mice to determine molecular mechanisms by which host androgen exposure promotes Escherichia coli pyelonephritis as well as renal scarring, a common sequela of upper-tract UTI. Our prior findings indicated that the influence of sex, including androgen exposure, on these common bacterial infections is more complex than previously appreciated. Specifically, male sex was associated with increased risk for chronic cystitis and high-titer pyelonephritis, as well as formation of renal abscesses. These snRNA-seq experiments were designed to interrogate the fundamental sex differences impacting the host-pathogen interaction and cellular responses in E. coli pyelonephritis, thereby influencing pathogenicity and outcome of infection.