Science

Pathogenesis of biofilm-associated infections

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Enterococci are a leading cause of hospital-acquired infections (HAIs), where they are frequent opportunistic pathogens of the urinary tract and wounds. These infections are often biofilm-associated, and thus, inherently more tolerant to antimicrobials and resistant to immune clearance. In addition, Enterococci are immunosuppressive, further complicating host clearance. The increasing prevalence of multidrug-resistant strains compounds treatment challenges, spurring efforts aimed at identifying novel intervention strategies to limit infection. Despite the prevalence of Enterococci in HAIs, its strategies for surviving and persisting in the host during infections are largely unknown. There is an urgent need to understand the host-pathogen interactions underlying Enterococcal infections because they will only become more prevalent as the global population ages and the incidence of correlated comorbidities continues to increase.

Our long-term goal is to identify, define, and harness mechanisms by which E. faecalis modulates and responds to the local host environment to promote infections in vivo. Historically considered an extracellular microbe, we have discovered that E. faecalis can also persist and replicate intracellularly. At the same time, extracellular E. faecalis can actively suppress macrophage and neutrophil activation. Our short-term goal is to identify the mechanisms by which E. faecalis suppresses and subverts host immune responses to promote intracellular survival and persistence, and to determine how intracellularity contributes to infection and disease progression in the mammalian host.

Expertise:

  • Animal models of bacterial biofilm-associated infection: wound infection, urinary tract infection, antibiotic-induced gut infection, infectious endocarditis
  • In vitro infection models for macrophages, neutrophils, and epithelial cells
  • Bacterial genetic manipulation
  • Polymicrobial infection models

Key publications:

17 Nov 2022

Host response to pathogens