E. faecalis normally resides as a gut commensal in humans, but thanks to its high resistance to antibiotics and other extracellular stresses, this Gram-positive bacterium has the potential to cause severe opportunistic infections. A critical mechanism used by the immune system in response to infection is phagocytic killing by macrophages and neutrophils. Our laboratory has identified that E. faecalis is readily able to evade phagocytosis; we have determined that an extracellular enterococcal polysaccharide antigen (EPA) produced by the bacterium plays a vital role conferring this ability. The aim of my project to is decipher the mechanisms in which EPA contributes to enterococcal survival and pathogenesis, including its role in evasion of phagocytosis. This will involve the combined skills of three different laboratories, investigating EPA and other aspects of enterococcal biology in vitro, in the context of a zebrafish model of infection, and when challenged by human macrophages. Given that E. faecalis is increasingly acquiring resistance to widely-used antibiotics, it is hoped that a better understanding of enterococcal pathogenesis will open up new avenues for therapeutic development. |
The Team
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