The DanRI regulatory system in uropathogenic Escherichia coli subverts neutrophil responses

Abstract

Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTI). 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 NET formation. Mechanistically, DanI functions as an antagonist to the transcriptional regulator DanR, thereby modulating key bacterial processes, including metabolic processes, flagellar biosynthesis, and stress response pathways. DanRI is required for UPEC fitness and long-term persistence in a mouse model of UTI. Taken together, our findings reveal DanRI as a novel regulatory system that promotes UPEC pathogenesis through immune evasion. Graphical abstract and model O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/658900v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@19095e6org.highwire.dtl.DTLVardef@1613c26org.highwire.dtl.DTLVardef@b415c3org.highwire.dtl.DTLVardef@100b79e_HPS_FORMAT_FIGEXP M_FIG C_FIG