Florent Ginhoux
Profile Url: florent-ginhoux
Researcher at Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore
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Infection and Immunity, 2017-09-11
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Infection and Immunity
Enterococcus faecalis is a member of the human gastrointestinal microbiota and is an opportunistic pathogen associated with hospital-acquired infections (HAIs) of wounds, the bloodstream, and the urinary tract. E. faecalis has the ability to subvert or evade immune-mediated clearance, although the mechanisms underlying this are poorly understood. In this study, we examine the ability of E. faecalis to subvert macrophage activation. We show that E. faecalis actively prevents NF-κB driven signaling in mouse RAW264.7 macrophages both in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coli. Co-infection with E. faecalis and E. coli in a mouse model of catheter-associated urinary tract infection (CAUTI) results in a reduced macrophage transcriptional response in the bladder compared to E. coli infection alone. Finally, we demonstrate that co-inoculation of E. faecalis with E. coli into the catheterized bladder significantly augments E. coli CAUTI. Taken together, these results implicate E. faecalis suppression of NF-κB-driven responses in macrophages with polymicrobial CAUTI pathogenesis.
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The Journal of Infectious Diseases, 2017-10-17
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Paper
Preprint
The Journal of Infectious Diseases
Enterococcus faecalis is one of most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics of E. faecalis and show that infected wounds result in two different states depending on the initial inoculum. Low dose inocula were associated with short term, low titer colonization whereas high dose inocula were associated with acute bacterial replication and long term persistence. High dose infection and persistence were also associated with immune cell infiltration, despite suppression of some inflammatory cytokines and delayed wound healing. During high dose infection, the multiple peptide resistance factor (MprF) which is involved in resisting immune clearance, contributes to E. faecalis fitness. These results comprehensively describe a mouse model for investigating E. faecalis wound infection determinants, and suggest that both immune modulation and resistance contribute to persistent, non-healing wounds.