title: The Rsb Phosphoregulatory Network Controls Availability of the Primary Sigma Factor in Chlamydia trachomatis and Influences the Kinetics of Growth and Development.
abstract: Chlamydia trachomatis is an obligate intracellular human pathogen that exhibits stage-specific gene transcription throughout a biphasic developmental cycle. The mechanisms that control modulation in transcription and associated phenotypic changes are poorly understood. This study provides evidence that a switch-protein kinase regulatory network controls availability of σ66, the main sigma subunit for transcription in Chlamydia. In vitro analysis revealed that a putative switch-protein kinase regulator, RsbW, is capable of interacting directly with σ66, as well as phosphorylating its own antagonist, RsbV1, rendering it inactive. Conversely, the putative PP2C-like phosphatase domain of chlamydial RsbU was capable of reverting RsbV1 into its active state. Recent advances in genetic manipulation of Chlamydia were employed to inactivate rsbV1, as well as to increase the expression levels of rsbW or rsbV1, in vivo. Representative σ66-dependent gene transcription was repressed in the absence of rsbV1 or upon increased expression of RsbW, and increased upon elevated expression of RsbV1. These effects on housekeeping transcription were also correlated to several measures of growth and development. A model is proposed where the relative levels of active antagonist (RsbV1) and switch-protein anti-sigma factor (RsbW) control the availability of σ66 and subsequently act as a molecular 'throttle' for Chlamydia growth and development.
authors: Jefferiss Trust Laboratories, Faculty of Medicine, Imperial College London, St. Mary's Hospital Campus, London, United Kingdom.
authors: Christopher C
authors: CC
authors: Thompson
authors: Jefferiss Trust Laboratories, Faculty of Medicine, Imperial College London, St. Mary's Hospital Campus, London, United Kingdom.
authors: Cherry
authors: C
authors: Griffiths
authors: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors: Sophie S
authors: SS
authors: Nicod
authors: Department of Microbiology, Southern Illinois University, Carbondale, Carbondale, Illinois, United States of America.
authors: Nicole M
authors: NM
authors: Lowden
authors: MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors: Sivaramesh
authors: S
authors: Wigneshweraraj
authors: Department of Microbiology, Southern Illinois University, Carbondale, Carbondale, Illinois, United States of America.
authors: Derek J
authors: DJ
authors: Fisher
authors: Jefferiss Trust Laboratories, Faculty of Medicine, Imperial College London, St. Mary's Hospital Campus, London, United Kingdom.
authors: Myra O
authors: MO
authors: McClure
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002692:Chlamydia trachomatis / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D012808:Sigma Factor / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C086522:RsbV protein, Bacteria; C080358:RsbW protein, bacteria; D012808:Sigma Factor; D000255:Adenosine Triphosphate