Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection

Abstract

Chlamydia trachomatis is an obligate intracellular pathogen that replicates inside a parasitic vacuole called the inclusion. The nascent inclusion is derived from the host plasma membrane and serves as a platform from which Chlamydia controls interactions with the host microenvironment. To survive inside the host cell, Chlamydia scavenges for nutrients and lipids by recruiting and/or fusing with various cellular compartments. The mechanisms by which these events occur are poorly understood but require host proteins such as the SNARE proteins (SNAP (Soluble N-ethylmaleimide-sensitive factor attachment protein) Receptor). Here, we show that SNAP-23 and Syntaxin 4, two plasma membrane SNAREs, are recruited to the inclusion and play an important role in Chlamydia development. Knocking down SNAP-23 and Syntaxin 4 by CRISPR-Cas9 reduces the amount of infectious progeny. We then demonstrate that the loss of both of these SNARE proteins results in the dysregulation of Chlamydia-induced lipid droplets, indicating that both SNAP-23 and Syntaxin 4 play a critical role in lipid droplet homeostasis during Chlamydia infection. Ultimately, our data highlights the importance of lipid droplets and their regulation in Chlamydia development.

Keywords

• lipid droplets
• chlamydia
• snare
• intracellular bacteria
• inclusion