Background

Chlamydiae are obligate intracellular pathogens that are a significant cause of morbidity in humans and animals. As an obligate intracellular pathogen, invasion and inclusion formation are essential for bacterial replication and chlamydial disease. Our laboratory studies how C. trachomatis type III secreted effector proteins hijack crucial host cell processes to facilitate host cell invasion, promote formation of its unique replicative niche within host cells, and subvert innate host defense mechanisms.

Our Current NIH Funded Projects

Role of C. trachomatis inclusion membrane proteins in manipulating host vesicular trafficking: 

All chlamydiae share a biphasic developmental cycle in which they alternate between an infectious, environmentally stable elementary body (EB) and a noninfectious, replicative form termed the reticulate body (RB). During infection, the EB is internalized into a membrane-bound compartment, termed the inclusion, that it immediately modifies through the incorporation of type III secreted effector proteins known as inclusion membrane proteins (Incs). All Incs possess a bi-lobed hydrophobic domain of ~30-40 amino acids and are inserted in the inclusion membrane such that their N- and C- termini are oriented into the host cell cytosol. Given their positioning at the host-pathogen interface, Incs mediate crucial interactions with the host cell. The importance of specific Inc proteins in forming and maintaining C. trachomatis unique intracellular niche is underscored by our recent study demonstrating that the absence of specific Inc proteins triggers premature inclusion lysis and host cell death. Using a combination of cellular, molecular, biochemical, and genetic techniques, we are addressing the role of these proteins in hijacking host vesicles to facilitate nutrient acquisition.

Role of conventional secreted effectors in host cell invasion:

As an obligate intracellular pathogen, host cell invasion is paramount to bacterial replication and initiation of disease. To force its way into nonphagocytic cells, C. trachomatis delivers select effector proteins into the host cell to coordinate membrane remodeling events necessary for infiltration. Effector proteins, including TarP and TmeA, have risen to prominence as crucial mediators of host cell invasion. Using molecular, cellular, and biochemical approaches, we are investigating how C. trachomatis effector proteins manipulate key cytoskeletal regulators to allow for pathogen uptake.