SINC, a secreted effector of Chlamydia psittaci, targets emerin and the nuclear envelope of infected cells and uninfected neighbors

Abstract

The chlamydial type III secretion system injects effector proteins into the host cell cytosol to facilitate bacterial growth and pathogenesis. We characterized SINC, a new effector produced by the avian and human pathogen, Chlamydia psittaci. SINC is syntenic with CT694 of Chlamydia trachomatis and likewise expressed late in development. However SINC uniquely targets the nuclear envelope (NE) of both C. psittaci-infected and uninfected neighboring cells. Digitonin permeabilization studies of infected or SINC-GFP-transfected HeLa cells suggest SINC targets the inner nuclear membrane (INM). Candidate partners were identified by proximity to biotin ligase-fused SINC (BirA-SINC) in HeLa cells and mass spectrometry (BioID). Among the most abundant peptides were fragments of INM proteins MAN1 and emerin, and of the nuclear pore complex protein, ELYS, suggesting candidate interacting partners at the NE. GFP-SINC association with the native LEM-domain protein emerin of the nuclear lamina was confirmed by GFP pull-down. SINC localization at the NE was blocked by importazole, confirming SINC import into the nucleus. My findings identify SINC as a novel effector that is transported to the NE of infected and neighboring uninfected cells where it targets emerin and potentially other proteins of the inner nuclear envelope. This association suggests that C. psittaci, an aggressive pathogen, has the capacity to modulate host cell nuclear functions, from chromatin organization to signaling and cytoskeletal regulation, both endogenously and exogenously.