Hijacking of Membrane Contact Sites by Intracellular Bacterial Pathogens.

Intracellular bacterial pathogens have evolved sophisticated mechanisms to hijack host cellular processes to promote their survival and replication inside host cells. Over the past two decades, much attention has been given to the strategies employed by these pathogens to manipulate various vesicular trafficking pathways. But in the past 5 years, studies have brought to light that intracellular bacteria also target non-vesicular trafficking pathways. Here we review how three vacuolar pathogens, namely, Legionella, Chlamydia, and Coxiella hijack components of cellular MCS with or without the formation of stable MCS. A common theme in the manipulation of MCS by intracellular bacteria is the dependence on the secretion of bacterial effector proteins. During the early stages of the Legionella life cycle, the bacteria connects otherwise unrelated cellular pathways (i.e., components of ER-PM MCS, PI4KIIIα, and Sac1 and the early secretory pathway) to remodel its nascent vacuole into an ER-like compartment. Chlamydia and Coxiella vacuoles establish direct MCS with the ER and target lipid transfer proteins that contain a FFAT motif, CERT, and ORP1L, respectively, suggesting a common mechanism of VAP-dependent lipid acquisition. Chlamydia also recruits STIM1, an ER calcium sensor involved in store-operated calcium entry (SOCE) at ER-PM MCS, and elucidating the role of STIM1 at ER-Chlamydia inclusion MCS may uncover additional role for these contacts. Altogether, the manipulation of MCS by intracellular bacterial pathogens has open a new and exciting area of research to investigate the molecular mechanisms supporting pathogenesis.