Chlamydia trachomatis effectors specifically modulate the landscape of the host cell: Dre1 interacts with dynactin to reposition host organelles during infection.

This thesis presents work toward understanding how the obligate intracellular pathogen, Chlamydia trachomatis, modulates the host cell to establish a protected replicative niche. In order to evade host-cell innate immune surveillance, internalized Chlamydia develop within a membrane-bound compartment referred to as the inclusion. Given that C. trachomatis relies on host-cell derived nutrients and energy, this bacterial pathogen must avoid globally inhibiting host-cell function while building what is essentially a novel organelle. Through strategic deployment of effectors into the host cytosol and inclusion membrane, C. trachomatis actively remodels host-cell structures from within the inclusion. This enables the bacteria to obtain the required metabolites and regulate specific organelle functions. This work focuses on: understanding which host proteins and cellular structures are repositioned around the growing inclusion; identifying which bacterial effectors are responsible for these modifications; and elucidating the mechanisms by which C. trachomatis calibrates organelle function to divert specific resources to the replicating bacteria while maintaining host viability.Until recently, the host targets of only a few Incs had been identified. We utilized high-throughput affinity purification-mass spectrometry to comprehensively define the Inc-human protein interactome, and discovered putative binding partners for 38/58 of the predicted C. trachomatis Incs. Using confocal immunofluorescence microscopy, we screened ~200 of the 335 identified high-confidence Inc-human protein-protein interactions for localization at the inclusion membrane, and we identified the recruitment of many host proteins involved in host processes consistent with Chlamydia’s intracellular life cycle. Thus, Chlamydia effectors recruit distinct subsets of host proteins to the inclusion, and mediate precise changes to the landscape of the host cell. In the first project, we characterized an interac