title: Chlamydia pneumoniae directly interferes with HIF-1alpha stabilization in human host cells.
abstract: Chlamydiaceae are obligate intracellular bacteria that cause endemic trachoma, sexually transmitted diseases and respiratory infections. The course of the diseases is determined by local inflammatory immune responses and the propensity of the pathogen to replicate within infected host cells. Both features require energy which is inseparably coupled to oxygen availability in the microenvironment. Hypoxia-inducible factor-1 (HIF-1) regulates crucial genes involved in the adaptation to low oxygen concentrations, cell metabolism and the innate immune response. Here we report that Chlamydia pneumoniae directly interferes with host cell HIF-1alpha regulation in a biphasic manner. In hypoxia, C. pneumoniae infection had an additive effect on HIF-1alpha stabilization resulting in enhanced glucose uptake during the early phase of infection. During the late phase of intracellular chlamydial replication, host cell adaptation to hypoxia was actively silenced by pathogen-induced HIF-1alpha degradation. HIF-1alpha was targeted by the chlamydial protease-like activity factor, which was secreted into the cytoplasm of infected cells. Direct interference with HIF-1alpha stabilization was essential for efficient C. pneumoniae replication in hypoxia and highlights a novel strategy of adaptive pathogen-host interaction in chlamydial diseases.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany. jan.rupp@uk-sh.de
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.forename: Jens
authors.initials: J
authors.lastname: Gieffers
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.forename: Ger
authors.initials: G
authors.lastname: van Zandbergen
authors.forename: Robert
authors.initials: R
authors.lastname: Wrase
authors.forename: Matthias
authors.initials: M
authors.lastname: Maass
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.forename: Joerg
authors.initials: J
authors.lastname: Deiwick
authors.forename: Thomas
authors.initials: T
authors.lastname: Hellwig-Burgel
mesh_terms: D015687:Cell Hypoxia; D002460:Cell Line; D002690:Chlamydia Infections / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit