title: The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites.
abstract: Bacterial pathogens that reside in membrane bound compartment manipulate the host cell machinery to establish and maintain their intracellular niche. The hijacking of inter-organelle vesicular trafficking through the targeting of small GTPases or SNARE proteins has been well established. Here, we show that intracellular pathogens also establish direct membrane contact sites with organelles and exploit non-vesicular transport machinery. We identified the ER-to-Golgi ceramide transfer protein CERT as a host cell factor specifically recruited to the inclusion, a membrane-bound compartment harboring the obligate intracellular pathogen Chlamydia trachomatis. We further showed that CERT recruitment to the inclusion correlated with the recruitment of VAPA/B-positive tubules in close proximity of the inclusion membrane, suggesting that ER-Inclusion membrane contact sites are formed upon C. trachomatis infection. Moreover, we identified the C. trachomatis effector protein IncD as a specific binding partner for CERT. Finally we showed that depletion of either CERT or the VAP proteins impaired bacterial development. We propose that the presence of IncD, CERT, VAPA/B, and potentially additional host and/or bacterial factors, at points of contact between the ER and the inclusion membrane provides a specialized metabolic and/or signaling microenvironment favorable to bacterial development.
authors: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America. isabelle.derre@yale.edu
authors: Isabelle
authors: I
authors: Derré
authors: Rachel
authors: R
authors: Swiss
authors: Hervé
authors: H
authors: Agaisse
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002689:Chlamydia / Q000737:chemistry*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D033921:Vesicular Transport Proteins
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D033921:Vesicular Transport Proteins; C030363:lipid transfer protein; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases