Research
Biofilm-tropic bacteriophage
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Biofilms are a hallmark of P. aeruignosa infections and are notoriously difficult to treat with antibiotics. We isolated a bacteriophage, Clew-1, that preferentially targets and kills P. aeruginosa in biofilms, compared to bacteria growing planktonically. It uses the exopolysaccharide Psl as a receptor. We are now asking how an exopolysaccharide can serve as a receptor. Are there other bacteriophage that preferentially target P. aeruignosa biofilms? Can these phage be used therapeutically to treat P. aeruginosa infections.
Role of ExoS and ExoT in inactivating Neutrophils
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We study P. aeruginosa pathogenesis in a corneal model of infection. Type III secretion is crucial for establishing an infection, and we recently demonstrated that injection of two effector proteins, ExoS and ExoT, is required for preventing ROS production by infiltrating neutrophils. ExoS blocks ROS production by ADP-ribosylating Ras, which prevents activation of PI3-kinase. We are currently studying how ExoT interferes with ROS production.
Translocon function
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The translocon is the structure through which effector proteins are injected into host cells. It consists of two pore-forming proteins, PopB and PopD, as well as the needle-tip (PcrV). While this structure is crucial for T3SS function, it has been very difficult to study in vitro. We have been using a genetic approach to identify protein-protein interactions in the translocon, and assigning them to translocon functions (such as translocator insertion, pore formation, and sensing of host cell contact). We recently discovered that triggering of effector secretion relies on a conformational change in the translocation pore, which is then transmitted to the needle-tip via specific protein-protein interactions with PcrV.