The role of Organelle Contact During Chlamydia Developmental Cycle

Abstract

Elucidating the molecular mechanisms supporting host‐pathogen interactions is a crucial step towards the eradication of infectious diseases. We study the obligate intracellular bacterium Chlamydia trachomatis, which is the leading cause of sexually transmitted infection of bacterial origin in the United States. Upon invading the epithelium of the genital tract, Chlamydia completes its life cycle in a membrane‐bound vacuole, called the inclusion. To convert the inclusion into an intracellular niche favorable for survival and replication, Chlamydia has evolved sophisticated mechanisms to manipulate the eukaryotic cell. Many studies have focused on understanding how Chlamydia, intercept the vesicular trafficking of the host cell. However, our laboratory has shed light on sites of intimate contact, with no fusion occurring, between the Chlamydia inclusion membrane and the endoplasmic reticulum (ER). Based on similarities to inter‐organelles membrane contact sites (MCS) observed in naïve cells, we refer to these structures as ER‐Inclusion MCS. Over the past several years, our lab has identified several molecular components of ER‐Inclusion MCS. More specifically, we have uncovered a role for Inc proteins (a subset of Chlamydia specific proteins that are embedded into the inclusion membrane) in the subversion of the endoplasmic reticulum. The recurrent theme is that, at ER‐Inclusion MCS, distinct Inc proteins mediate the recruitment of and associate with specific host factors that usually associate to distinct MCS in naïve cells. Here, we will discuss our current understanding of how these Inc protein‐host factor complexes contribute to the formation and function of ER‐Inclusion MCS and the establishment of Chlamydia replicative niche.Support or Funding InformationThis work is supported by NIH‐NIAID grants R01 AI101441, R21 AI141841 and R03 AI146649.