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The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression

Author

Listed:
  • Sara Jakob

    (University of Marburg)

  • Wieland Steinchen

    (University of Marburg
    Center for Synthetic Microbiology (SYNMIKRO))

  • Juri Hanßmann

    (University of Marburg
    Max Planck Institute for Terrestrial Microbiology)

  • Julia Rosum

    (University of Marburg)

  • Katja Langenfeld

    (Max Planck Institute for Terrestrial Microbiology)

  • Manuel Osorio-Valeriano

    (University of Marburg
    Blavatnik Institute, Harvard Medical School)

  • Niklas Steube

    (Evolutionary Biochemistry Group, Max Planck Institute for Terrestrial Microbiology)

  • Pietro I. Giammarinaro

    (University of Marburg
    Heidelberg University Biochemistry Center (BZH))

  • Georg K. A. Hochberg

    (University of Marburg
    Center for Synthetic Microbiology (SYNMIKRO)
    Evolutionary Biochemistry Group, Max Planck Institute for Terrestrial Microbiology)

  • Timo Glatter

    (Max Planck Institute for Terrestrial Microbiology)

  • Gert Bange

    (University of Marburg
    Center for Synthetic Microbiology (SYNMIKRO)
    Max Planck Institute for Terrestrial Microbiology)

  • Andreas Diepold

    (Max Planck Institute for Terrestrial Microbiology)

  • Martin Thanbichler

    (University of Marburg
    Center for Synthetic Microbiology (SYNMIKRO)
    Max Planck Institute for Terrestrial Microbiology)

Abstract

The transcriptional antisilencer VirB acts as a master regulator of virulence gene expression in the human pathogen Shigella flexneri. It binds DNA sequences (virS) upstream of VirB-dependent promoters and counteracts their silencing by the nucleoid-organizing protein H-NS. However, its precise mode of action remains unclear. Notably, VirB is not a classical transcription factor but related to ParB-type DNA-partitioning proteins, which have recently been recognized as DNA-sliding clamps using CTP binding and hydrolysis to control their DNA entry gate. Here, we show that VirB binds CTP, embraces DNA in a clamp-like fashion upon its CTP-dependent loading at virS sites and slides laterally on DNA after clamp closure. Mutations that prevent CTP-binding block VirB loading in vitro and abolish the formation of VirB nucleoprotein complexes as well as virulence gene expression in vivo. Thus, VirB represents a CTP-dependent molecular switch that uses a loading-and-sliding mechanism to control transcription during bacterial pathogenesis.

Suggested Citation

  • Sara Jakob & Wieland Steinchen & Juri Hanßmann & Julia Rosum & Katja Langenfeld & Manuel Osorio-Valeriano & Niklas Steube & Pietro I. Giammarinaro & Georg K. A. Hochberg & Timo Glatter & Gert Bange & , 2024. "The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44509-z
    DOI: 10.1038/s41467-023-44509-z
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    References listed on IDEAS

    as
    1. Lara Connolley & Lucas Schnabel & Martin Thanbichler & Seán M. Murray, 2023. "Partition complex structure can arise from sliding and bridging of ParB dimers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
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