The DanRI regulatory system in uropathogenic Escherichia coli subverts neutrophil responses.

Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). To establish an infection, UPEC must evade infiltrating neutrophils and their antimicrobial neutrophil extracellular traps (NETs). In this study, we identify a previously uncharacterized two-gene regulatory system within the pathogenicity island PAIUTI89II, which we named DanRI (defense against neutrophil regulator and inhibitor). DanRI is induced by nucleosomes present in NETs and enables UPEC to suppress neutrophil responses by attenuating reactive oxygen species production and subsequent NET formation. Mechanistically, DanI functions as an antagonist to the transcriptional regulator DanR, thereby modulating key bacterial processes, including metabolic, flagellar biosynthesis, and stress response pathways. DanRI enhances UPEC fitness by dampening the early host inflammatory response during UTI in a mouse model. Taken together, these findings reveal DanRI as a regulatory system that promotes UPEC pathogenesis by facilitating immune evasion.