Bacterial Outer Membrane Vesicles

and Inflammation

The goal of this project is to determine how bacterial outer membrane vesicles (OMVs) from pathogenic vs. commensal bacteria communicate with host cells to control inflammation. In this project we are using the model organism Bacteroides fragilis. (Funded by the National Institutes of Health Research Enhancement Award (R15))

Background

    • Colon cancer has been linked to inflammation
    • The microbiome influences intestinal homeostasis
    • Bacteroides fragilis exists as commensal (NTBF) and pathogen (ETBF) strains, which are linked to distinct health outcomes

    Hypothesis

    ETBF and NTBF shed outer membrane vesicles (OMVs) that mediate distinct downstream signaling outcomes through engagement with multiple toll-like receptors (TLRs) on host epithelial cells.

    Specific Aims

    1: Elucidate the differential activation of the innate immune response between commensal and enterotoxigenic OMVs from B. fragilis using an established tri-culture system.

    2: Identify the mechanism of immune-stimulating intracellular uptake and sub-cellular localization from commensal vs. enterotoxigenic B. fragilis OMVs into host cells.

    3: Determine the commensal vs. enterotoxigenic B. fragilis small RNA host targets in silico using bioinformatics tools and validate in vitro using tri-culture and nanolipovesicle transfection.