Washington University School of Medicine
Department of Molecular Microbiology
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Research in our lab is directed at elucidating molecular mechanisms of interaction between the intracellular bacterial pathogen Chlamydia and its host cell. Chlamydiae have adapted an intracellular developmental cycle that takes place entirely within the confines of a membrane-bound parasitophorous vacuole, termed an inclusion. Within this environment, these bacterial pathogens coordinate the expansion of the inclusion and the generation/acquisition of biosynthetic building blocks essential for their propagation and subsistence. Although chlamydiae remain largely segregated from the host cytosol, the recruitment of key regulators of membrane trafficking and the association with nutrient-rich eukaryotic organelles suggest an interaction that is not passive.

Work in our lab has identified a novel interaction between chlamydiae and the host cell’s multivesicular bodies (MVBs), lipid- and cholesterol-rich late endosomes, which are pivotal in the segregation of host-derived proteins and lipids. In addition to their functional attributes, MVBs intersect the endosome-lysosome, autophagy, and exocytic pathways, making these organelles ideally positioned to interact with the chlamydial inclusion. Using a cell biological approach, tracers, specific markers, and available inhibitors are being utilized to analyze resident protein and lipid constituents of MVB-associated pathways in order to define their interactions with the chlamydial inclusion. In addition, the lab is exploring multiple inhibitory approaches to manipulate intracellular trafficking pathways and analyze subsequent effects on protein and lipid delivery to the maturing chlamydial inclusion. Identification and characterization of chlamydial inclusion influx pathways and corresponding requisite host factors, will have important implications on the development of therapeutic intervention targeting nutrient acquisition pathways essential for intracellular sequestration and maturation of these successful microbial pathogens.

 

 

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