title: 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.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA. beatty@borcim.wustl.edu
authors.forename: Wandy L
authors.initials: WL
authors.lastname: Beatty
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000166:cytology / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; C554586:CD63 protein, human; C554587:Cd63 protein, mouse; D004396:Coloring Agents; C460868:IncA protein, Chlamydia trachomatis; D052118:Lysosomal-Associated Membrane Protein 1; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D013109:Sphingomyelins; D060149:Tetraspanin 30