Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection

Infect Immun. 2017 Nov 17;85(12):e00378-17. doi: 10.1128/IAI.00378-17. Print 2017 Dec.

Abstract

Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. E. faecalis can subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examined E. faecalis-mediated subversion of macrophage activation. We observed that E. faecalis actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coliE. faecalis and E. coli coinfection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to that with E. coli infection alone. Finally, we demonstrated that coinoculation of E. faecalis with a commensal strain of E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support the hypothesis that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis, especially during coinfection with less virulent or commensal E. coli strains.

Keywords: Enterococcus faecalis; Escherichia coli; catheter-associated UTI; coinfection; immune suppression; macrophage; polymicrobial; urinary tract infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catheter-Related Infections / microbiology*
  • Coinfection / microbiology*
  • Disease Models, Animal
  • Enterococcus faecalis / immunology*
  • Enterococcus faecalis / physiology*
  • Escherichia coli Infections / complications
  • Escherichia coli Infections / microbiology
  • Gram-Positive Bacterial Infections / complications
  • Gram-Positive Bacterial Infections / microbiology
  • Immune Tolerance*
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • NF-kappa B / metabolism
  • RAW 264.7 Cells
  • Signal Transduction
  • Urinary Tract Infections / microbiology*

Substances

  • NF-kappa B