IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44509-z.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44509-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44509-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Katarzyna Pawlikiewicz & Agnieszka Strzałka & Michał Majkowski & Julia Duława-Kobeluszczyk & Marcin J. Szafran & Dagmara Jakimowicz, 2025. "SMC modulates ParB engagement in segregation complexes in streptomyces," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    2. Lucas Schnabel & Manuel Osorio-Valeriano & Cecilia Perez-Borrajero & Wieland Steinchen & Christopher-Nils Mais & Bernd Simon & Juri Hanßmann & Maria Thamm & Janosch Hennig & Gert Bange & Martin Thanbi, 2025. "Molecular basis of ParA ATPase activation by the CTPase ParB during bacterial chromosome segregation," Nature Communications, Nature, vol. 16(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44509-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.