Therapeutic Targeting of Enterococcal Infection
The rise of multidrug-resistant Enterococci, especially in the context of chronic and biofilm-associated infections, has highlighted the urgent need for alternative treatment strategies. Traditional antibiotics often fail to clear infection due to both inherited resistance mechanisms and non-heritable phenotypes such as biofilm-associated tolerance and intracellular persistence. As a result, our lab is focused on developing therapeutic approaches that move beyond standard antimicrobials and instead target enterococci through multiple, complementary mechanisms.
We are investigating bacteriophages and phage-derived enzymes as precision tools to selectively eliminate E. faecalis, including in polymicrobial communities and antibiotic-refractory settings. In parallel, we explore immunomodulatory approaches designed to enhance host innate defenses or restore effective immune responses suppressed during infection. This includes strategies to boost phagocyte activity, modulate cytokine signaling, and disrupt immune subversion by bacterial factors.
Our work also includes the development of combinatorial therapies that integrate phage, immune modulators, and sub-inhibitory antibiotics to achieve synergistic clearance of infection. In addition, we are examining anti-virulence strategies that disarm key factors such as biofilm formation, adhesion, and immune evasion without directly killing the bacteria – thus minimizing selective pressure for resistance.
These interventions are tested in preclinical models of urinary tract infection, wound infection, and endocarditis. By leveraging mechanistic insights into both bacterial pathogenesis and host response, our goal is to define therapeutic combinations that are more effective, more durable, and better suited to the challenges of treating drug-resistant Enterococcal infections.
