Host cysteine proteases promote the severity of catheter-associated urinary tract infection and kidney fibrosis.

ABSTRACT: The bacterium Enterococcus faecalis is a leading cause of catheter-associated urinary tract infection (CAUTI), whose treatment is increasingly challenged by antibiotic resistance. In examining alternative therapies, we previously found that the cysteine protease inhibitor E64 dramatically reduced bladder inflammation and bacterial dissemination in a murine model of E. faecalis CAUTI. However, the role of cysteine proteases in pathogenesis and the target(s) of E64 are unknown. Here, we found that while it did not affect E. faecalis growth in vitro, in a murine CAUTI model, E64 reduced host caspase-1-dependent cellular apoptosis and necrosis, levels of several pro-inflammatory cytokines, bladder epithelial damage, and formation of renal abscesses. Analysis of host

SUBMITTER: Xu W 

PROVIDER: S-EPMC12607876 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature