title: Dynamin-mediated lipid acquisition is essential for Chlamydia trachomatis development.
abstract: Chlamydia trachomatis is an obligate intracellular pathogen responsible for a high burden of human disease. Here, a loss-of-function screen using a set of lentivirally transduced shRNAs identified 14 human host cell factors that modulate C. trachomatis infectivity. Notably, knockdown of dynamin, a host GTPase, decreased C. trachomatis infectivity. Dynamin functions in multiple cytoplasmic locations, including vesicle formation at the plasma membrane and the trans-Golgi network. However, its role in C. trachomatis infection remains unclear. Here we report that dynamin is essential for homotypic fusion of C. trachomatis inclusions but not for C. trachomatis internalization into the host cell. Further, dynamin activity is necessary for lipid transport into C. trachomatis inclusions and for normal re-differentiation from reticulate to elementary bodies. Fragmentation of the Golgi apparatus is proposed to be an important strategy used by C. trachomatis for efficient lipid acquisition and replication within the host. Here we show that a subset of C. trachomatis-infected cells displayed Golgi fragmentation, which was concurrent with increased mitotic accumulation. Golgi fragmentation was dispensable for dynamin-mediated lipid acquisition into C. trachomatis inclusions, irrespective of the cell cycle phase. Thus, our study reveals a critical role of dynamin in host-derived lipid acquisition for C. trachomatis development.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.
authors.forename: Rajendra Kumar
authors.initials: RK
authors.lastname: Gurumurthy
authors.forename: Cindrilla
authors.initials: C
authors.lastname: Chumduri
authors.forename: Alexander
authors.initials: A
authors.lastname: Karlas
authors.forename: Sonja
authors.initials: S
authors.lastname: Kimmig
authors.forename: Erik
authors.initials: E
authors.lastname: Gonzalez
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Machuy
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
mesh_terms: D002690:Chlamydia Infections / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism*; D034285:Dynamin II; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D050356:Lipid Metabolism
chemical_list: D034284:Dynamin I; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins