Abstract 2277 Membrane contact sites and Chlamydia infections

Elucidating the molecular mechanisms supporting host-pathogen interactions is a crucial step towards the eradication of infectious diseases. We study the obligate intracellular bacterium Chlamydia trachomatis, which is the leading cause of sexually transmitted infections of bacterial origin. Upon invading the epithelial cells of the genital tract, Chlamydia completes its life cycle within a membrane-bound vacuole, called the inclusion. Inc proteins, a subset of Chlamydia specific proteins that are embedded into the inclusion membrane, facilitate the maturation of the inclusion into a unique and pro-survival compartment. Our laboratory showed that subdomains of the Chlamydia inclusion membrane establish membrane contact sites (MCS) with the endoplasmic reticulum (ER). We aim to functionally link ER-Inclusion MCS to the establishment of the Chlamydia replicative niche, and to pathogenesis. We will discuss our progress towards uncovering the role of distinct Inc protein-host factors complexes in the formation and function of ER-Inclusion MCS. Specifically, how bacterial molecular mimicry of eukaryotic motifs, such as FFAT motifs and kinase consensus sequences, leads to the assembly of the IncV-VAP regulated tether; how ceramide transfer from the ER to the inclusion, via the IncD-CERT-VAP complex, is essential for bacterial growth; and how the IncS-STIM1 complex influences bacterial development. Altogether, our work provides a unique perspective on the study of MCS, by investigating how direct membrane contact between bacterial pathogen containing vacuoles and host organelles mediates host-pathogens interactions.