How bacteria corrupt the host vesicular trafficking: Interfering with host SNAREs

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DESCRIPTION (provided by applicant): Chlamydia trachomatis is an intracellular bacterium that is a major cause of sexually transmitted diseases and infectious blindness. Chlamydia's survival largely relies on two fundamental processes 1) protecting its infectious intracellular compartment (so-called inclusion) from the lysosomal degradative pathway and 2) hijacking host compartments to acquire nutrients and material necessary to grow the inclusion. To perform both these events, C. trachomatis evolved to be extraordinarily efficient at manipulating membrane fusion and promote its survival. Despite the importance of this intimate connection between Chlamydia and host vesicular trafficking, very little is known regarding the impact of this bacterium on the host membrane fusion machinery, the so-called SNAREs. Do Chlamydiae extensively co-opt SNAREs to control the host vesicular trafficking and promote their survival inside the cell? Using an innovative multidisciplinary approach, we seek to determine whether C. trachomatis (i) uses multiple SNARE-like proteins to sequentially block different host SNARE complexes involved in the endocytic/lysosomal pathway and protect its inclusion from destruction and (ii) recruits host SNAREs involved in the secretory pathway to hijack host vesicles and promote the growth of its inclusion. The characterization of multiple chlamydial SNARE-like proteins will give scientists the fundamental tools to screen for their presence in the proteome of other major human pathogens, including Salmonella typhi, and Mycobacterium tuberculosis, thus opening new avenues of research.