Using a Zebrafish Model to Identify Cellular Responses to Uropathogenic E. coli Bacteremia

Urinary tract infections (UTIs) are the second most common infections encountered in the pediatric population, second only to respiratory tract infections. UTIs are also a major cause of morbidity and mortality. UTIs can often ascend causing infection in the upper urinary tract or even progress to bacteremia or urosepsis. Urosepsis accounts for 10-30% of septic shock cases and Uropathogenic E.coli (UPEC) is responsible for almost 75% of cases. Therefore, increased understanding of the effects of urosepsis at the cellular and organ specific level will provide the foundation for improvements in clinical care. Overall design: Two zebrafish cohorts were injected with either sterile saline or UPEC and subjected to scRNA-seq. Cell clusters were identified and subjected to RNA velocity analysis. Selected clusters relevant to the innate immune system and bactericidal activity underwent canonical pathway analysis. RNA velocity analysis revealed several key changes in the transcriptional state of UPEC infected cells and pathway analysis provided key information regarding changes in innate immune pathways within the cell clusters.