Trafficking from CD63-positive late endocytic multivesicular bodies is essential for intracellular development of Chlamydia trachomatis

Abstract

Chlamydiae are obligate intracellular bacterial pathogens that replicate solely within the confines of a membrane-bound vacuole termed an inclusion. Within this protected organelle, chlamydiae acquire host-cell-derived biosynthetic precursors necessary for intracellular subsistence, yet the mechanisms and pathways responsible for this acquisition remain elusive. The present study identifies an interaction between the chlamydial inclusion and multivesicular bodies, complex organelles pivotal in protein and lipid transport that are positioned along the endosome-lysosome pathway, and intersect the exocytic pathway in various cell types. Resident protein and lipid constituents of multivesicular bodies colocalized with intracellular chlamydiae, with direct delivery of the resident protein CD63 to the chlamydial inclusion. Interruption of trafficking from multivesicular bodies by pharmacological inhibitors and exogenous antibodies subsequently disrupted sphingolipid delivery to the maturing chlamydial inclusion and intracellular bacterial growth. This study identifies a trafficking pathway from CD63-positive multivesicular bodies to the bacterial inclusion, a novel interaction that provides essential lipids necessary for maintenance of a productive intracellular infection.

Chlamydial Intracellular Survival Strategies

“…In addition to the Golgi, the inclusion interacts with other host-cell organelles, including (1) multivesicular bodies (MVBs) (Beatty 2006(Beatty , 2008Robertson et al 2009), which may also serve as a source of sphingolipids and cholesterol, (2) lipid droplets, which are translocated into the inclusion lumen following their capture by the chlamydial proteins Lda1 and/or Lda3 and which may serve as a source of neutral lipids (Kumar et al 2006;Cocchiaro et al 2008), (3) mitochondria (Matsumoto et al 1991;Derre et al 2007), and (4) lysosomes, which may be a source of essential amino acids derived from host-protein degradation (Ouellette et al 2011). Together, these interactions (summarized in Fig.…”

Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole

“…Chlamydia efficiently acquires host-derived membrane lipids such as glycerophospholipids (4), sphingolipids (5), and cholesterol (6) by selectively rerouting Golgi-derived exocytic vesicles (7) and multivesicular bodies (MVB) (8). However, membrane lipids are also transported to the inclusion via nonvesicle mediated pathways.…”

A small-molecule inhibitor of type III secretion inhibits different stages of the infectious cycle of Chlamydia trachomatis

“…Upon EB release from the infected host cell, a new round of infection can begin. Throughout their entire time in the host cell, Chlamydia remain within the confinements of the parasitophorous vacuole, which very early during infection exits the endocytic pathway and becomes instead fusiogenic with a subset of exocytic vesicles originating from the ER͞Golgi network and late endosomes (6,7).…”