Enterococcus faecalis overcomes foreign body-mediated inflammation to establish urinary tract infections.

ABSTRACT: Urinary catheterization elicits major histological and immunological changes that render the bladder susceptible to microbial invasion, colonization, and dissemination. However, it is not understood how catheters induce these changes, how these changes act to promote infection, or whether they may have any protective benefit. In the present study, we examined how catheter-associated inflammation impacts infection by Enterococcus faecalis, a leading cause of catheter-associated urinary tract infection (CAUTI), a source of significant societal and clinical challenges. Using a recently optimized murine model of foreign body-associated UTI, we found that the implanted catheter itself was the primary inducer of inflammation. In the absence of the silicone tubing implant, E. faecalis induced only minimal inflammation and was rapidly cleared from the bladder. The catheter-induced inflammation was only minimally altered by subsequent enterococcal infection and was not suppressed by inhibitors of the neurogenic pathway and only partially by dexamethasone. Despite the robust inflammatory response induced by urinary implantation, E. faecalis produced biofilm and high bladder titers in these animals. Induction of inflammation in the absence of an implanted catheter failed to promote infection, suggesting that the presence of the catheter itself is essential for E. faecalis persistence in the bladder. Immunosuppression prior to urinary catheterization enhanced E. faecalis colonization, suggesting that implant-mediated inflammation contributes to the control of enterococcal infection. Thus, this study underscores the need for novel strategies against CAUTIs that seek to reduce the deleterious effects of implant-mediated inflammation on bladder homeostasis while maintaining an active immune response that effectively limits bacterial invaders.

SUBMITTER: Guiton PS 

PROVIDER: S-EPMC3536162 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature