A single chlamydial protein reshapes the plasma membrane and serves as recruiting platform for central endocytic effector proteins.

Uptake of obligate intracellular bacterial pathogens into mammalian epithelial cells is critically dependent on modulation of the host's endocytic machinery. It is an open question how the invading pathogens generate a membrane-bound vesicle appropriate to their size. This requires extensive deformation of the host plasma membrane itself by pathogen-derived membrane-binding proteins, accompanied by substantial F-actin-based forces to further expand and finally pinch off the vesicle. Here we show that upon adhesion to the host cell, the human pathogenic bacterium Chlamydia pneumoniae secretes the scaffolding effector protein CPn0677, which binds to the inner leaflet of the invaginating host's PM, induces inwardly directed, negative membrane curvature, and forms a recruiting platform for the membrane-deforming BAR-domain containing proteins Pacsin and SNX9. In addition, while bound to the membrane, CPn0677 recruits monomeric G-actin, and its C-terminal region binds and activates N-WASP, which initiates branching actin polymerization via the Arp2/3 complex. Together, these membrane-bound processes enable the developing endocytic vesicle to engulf the infectious elementary body, while the associated actin network generates the forces required to reshape and detach the nascent vesicle from the PM. Thus, Cpn0677 (now renamed SemD) acts as recruiting platform for central components of the endocytic machinery during uptake of chlamydia.