Enterococcus faecalispromotes innate immune suppression and polymicrobial catheter-associated urinary tract infection

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 coli. E. faecalis and E. coli co-infection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to E. coli infection alone. Finally, we demonstrated that co-inoculation of E. faecalis with E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis.Author SummarySynergistic polymicrobial infections can contribute to both disease severity and persistence. Enterococcus faecalis and Escherichia coli are frequently co-isolated from polymicrobial urinary tract infections. Immunomodulation by co-infecting microbes can result in a more permissive environment for pathogens to establish infection. Presently, we do not yet understand how these microbes overcome host immunity to establish polymicrobial infections. To address this, we investigated how the immunosuppressive function of E. faecalis can contribute to acute infection. We defined that E. faecalis is able to suppress macrophages in vitro, despite the presence of E. coli. We also demonstrated E. faecalis’ ability to augment E. coli titers in vivo to establish kidney infection. Our findings raise the prospect that E. faecalis can alter host immunity to increase susceptibility to other uropathogens.

Urinary Tract Infection Caused By Enterococcus Spp: Risk Factors And Mortality. An Observational Study.

“…Bacteriuria caused by enterococci has a deleterious effect on the urinary tract, which promotes innate immune suppression and increases the risk of infection by other uropathogens (13), suggesting that the treatment of AB can be successful in terms of the prevention of the recurrence of urinary tract infection. Nevertheless, paradoxically, it has been shown that antibiotic treatment of AB caused by Enterococcus, in patients with recurrent infection, increases the risk for recurrent urinary infection by other uropathogens (14).…”

Urinary tract infection caused by enterococcus spp: risk factors and mortality.

“…UTIs. Bacteriuria caused by enterococci has a deleterious effect on the urinary tract, which promotes innate immune suppression and increases the risk of infection by other uropathogens (13), suggesting that the treatment of AB can be successful in terms of the prevention of the recurrence of urinary tract infection. Nevertheless, paradoxically, it has been shown that antibiotic treatment of AB caused by Enterococcus, in patients with recurrent infection, increases the risk for recurrent urinary infection by other uropathogens (14).…”

Microbial Evolutionary Medicine – from theory to clinical practice

“…Further, pathogen diversity and order of arrival can affect disease severity. In urinary tract infections, for example, E. faecalis is able to facilitate the invasion of otherwise avirulent E. coli in an animal colonization model, and can even impact disease development after it is cleared (79). The stochastic nature of arrival may therefore play a role in the ecology, as not all bacteria are able to colonize the host in any order (80).…”