title: A Chlamydia effector recruits CEP170 to reprogram host microtubule organization.
abstract: The obligate intracellular bacterial pathogen Chlamydia trachomatis deploys virulence effectors to subvert host cell functions enabling its replication within a specialized membrane-bound compartment termed an inclusion. The control of the host cytoskeleton is crucial for Chlamydia uptake, inclusion biogenesis and cell exit. Here, we demonstrate how a Chlamydia effector rearranges the microtubule (MT) network by initiating organization of the MTs at the inclusion surface. We identified an inclusion-localized effector that is sufficient to interfere with MT assembly, which we named inclusion protein acting on MTs (IPAM). We established that IPAM recruits and stimulates the centrosomal protein 170 kDa (CEP170) to hijack the MT organizing functions of the host cell. We show that CEP170 is essential for chlamydial control of host MT assembly, and is required for inclusion morphogenesis and bacterial infectivity. Together, we demonstrate how a pathogen effector reprograms the host MT network to support its intracellular development.
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, UK.
authors.forename: Maud
authors.initials: M
authors.lastname: Dumoux
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, UK.
authors.forename: Anais
authors.initials: A
authors.lastname: Menny
authors.affiliation: Cell Adhesion and Mechanics Group, Institut Jacques Monod, CNRS UMR7592, Université Paris Diderot, 15 rue Helene Brion, Paris 75013, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Delacour
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, UK richard.hayward@ucl.ac.uk.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Hayward
mesh_terms: D002690:Chlamydia Infections / Q000378:metabolism / Q000473:pathology; D002692:Chlamydia trachomatis; D003599:Cytoskeleton / Q000473:pathology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D002479:Inclusion Bodies / Q000382:microbiology*; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism*
chemical_list: C502822:Cep170 protein, human; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins
keywords: CEP170; Centrosome; Chlamydia; Microtubules; Type III secretion