TY - JOUR T1 - Extrusions promote engulfment and <em>Chlamydia</em> survival within macrophages JF - bioRxiv DO - 10.1101/041079 SP - 041079 AU - Meghan Zuck AU - Tisha Ellis AU - Anthony Venida AU - Kevin Hybiske Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/02/23/041079.abstract N2 - All obligate intracellular pathogens must exit their host cells in order to propagate and survive as a species; the precise strategies they use have a direct impact on their ability to disseminate within a host, transmit to new hosts, and engage or avoid immune responses. The obligate intracellular bacterium Chlamydia trachomatis exits the host cell by two distinct exit strategies, lysis and extrusion. Despite being equally active pathways, lysis and extrusion differ greatly in their mechanisms. The defining characteristics of extrusions, and advantages gained by Chlamydia within this unique double-membrane structure are not well understood. Here, we present data that defines extrusions as being largely devoid of host organelles, comprised mostly of Chlamydia elementary bodies, and containing phosphatidylserine on the outer surface of the extrusion membrane. Towards defining a functional role for extrusions in Chlamydia pathogenesis, we demonstrate that extrusions confer significant infectious advantages for Chlamydia by serving as transient, intracellular-like niches for extracellular Chlamydia, as compared to Chlamydia that would otherwise exit by lysing the host cell. In addition to enhanced survival outside of the host cell, we report the key discovery that chlamydial extrusions can be engulfed by primary bone marrow-derived macrophages, after which they provide a protective microenvironment for Chlamydia. Extrusion-derived Chlamydia were able to stave off macrophage based killing beyond 8 h, and culminated in the release of infectious EB from the macrophage. Based on these findings, we propose a model in which a major outcome of Chlamydia exiting epithelial cells inside extrusions is to hijack macrophages as vehicles for dissemination within the host. ER -