Mechanisms of enterococcus faecalis-mediated Immunomodulation

• Main Author: Kao, Patrick Hsien-Neng
• Other Authors: -
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2022
• Subjects: Science::Biological sciences::Microbiology::Bacteria
• Online Access: https://hdl.handle.net/10356/160631
• Institution: Nanyang Technological University

Enterococci are a major cause of hospital-acquired infections with Enterococcus faecalis and Enterococcus faecium frequently found as a component of chronic, polymicrobial infections alongside other bacteria. This study explores interactions between innate immune cells and E. faecalis, with a focus on identifying both effective responses deployed by these cells to eliminate the bacteria, as well as specific immunomodulating mechanisms utilized by E. faecalis to evade clearance. E. faecalis induced large amount of reactive oxygen species (ROS) production in neutrophils. When co-infection with potent NET-inducer S. aureus, E. faecalis both reduced S. aureus-induced NETosis and promoted S. aureus survival. This points to the possible collaboration mechanisms underpinning the persistence of chronic, polymicrobial infection with these two bacterial strains. E. faecalis was reported to suppress LPS-induced NF-κB activation, so a transposon library screening was conducted to identify the mutants that failed to reach a similar level of activity reduction. This screen identified that shikimic acid pathway promoted E. faecalis-driven cytotoxicity in macrophages, likely by inducing apoptosis and thus reduced the overall immune activity such as cytokine production. Collectively, these findings provide clues behind the high correlation of E. faecalis with S. aureus in persistent polymicrobial infections. It furthermore illustrated key mechanisms utilized by E. faecalis to subvert the antimicrobial mechanisms of both murine neutrophils and macrophages directly. These findings have important implications for our understanding of E. faecalis host-pathogen interactions, most importantly through the identification of potential targets which may serve to interrupt E. faecalis immune evasion.