title: Modulation of the host transcriptome by Coxiella burnetii nuclear effector Cbu1314.
abstract: Coxiella burnetii is a Gram-negative, obligate intracellular pathogen that directs the formation of a parasitophorous vacuole derived from the host lysosomal network. Biogenesis and maintenance of this replicative compartment is dependent on bacterial protein synthesis and results in differential expression of specific host genes. However, the mechanisms by which the pathogen induces changes in the host transcriptome is poorly understood. In the current study we identified a Dot/Icm secreted effector, Cbu1314, which encodes two nuclear localization signals that are required for nuclear localization and association with host chromatin. Chromatin immunoprecipitation (ChIP) and deep sequencing revealed that Cbu1314 associated with host genes involved in transcription, cell signaling, and the immune response. RNA sequencing of cells overexpressing Cbu1314 demonstrated that Cbu1314 modulates the host transcriptome and these transcriptional changes required a functional nuclear localization signal. Of the differentially expressed genes, sixteen were also identified as Cbu1314 targets using ChIP sequencing. Collectively these results suggest that Cbu1314 associates with host chromatin and plays a role in modulating the host transcriptome.
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Weber
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Faris
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA.
authors.forename: Juanita
authors.initials: J
authors.lastname: McLachlan
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Tellez
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA.
authors.forename: William U
authors.initials: WU
authors.lastname: Wright
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Galvan
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Luo
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA. Electronic address: jsamuel@medicine.tamhsc.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Samuel
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D016997:Coxiella burnetii / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D054884:Host-Pathogen Interactions; D006801:Humans; D019913:Nuclear Localization Signals; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; D002843:Chromatin; D019913:Nuclear Localization Signals
keywords: Coxiella burnetii; Dot/Icm; Nuclear effector; T4SS