IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60871-6.html
   My bibliography  Save this article

The virulence regulator CovR boosts CRISPR-Cas9 immunity in Group B Streptococcus

Author

Listed:
  • Adeline Pastuszka

    (UMR
    Service de Bactériologie-Virologie)

  • Maria-Vittoria Mazzuoli

    (Department of Microbiology)

  • Chiara Crestani

    (Department of Global Health)

  • Léonie Deborde

    (Department of Microbiology)

  • Odile Sismeiro

    (Department of Microbiology)

  • Coralie Lemaire

    (UMR
    Service de Bactériologie-Virologie)

  • Vanessa Rong

    (UMR)

  • Myriam Gominet

    (Department of Microbiology)

  • Elise Jacquemet

    (Bioinformatics and Biostatistics Hub)

  • Rachel Legendre

    (Bioinformatics and Biostatistics Hub)

  • Philippe Lanotte

    (UMR
    Service de Bactériologie-Virologie)

  • Arnaud Firon

    (Department of Microbiology)

Abstract

CRISPR-Cas9 immune systems protect bacteria from foreign DNA. However, immune efficiency is constrained by Cas9 off-target cleavages and toxicity. How bacteria regulate Cas9 to maximize protection while preventing autoimmunity is not understood. Here, we show that the master regulator of virulence, CovR, regulates CRISPR-Cas9 immunity against mobile genetic elements in Streptococcus agalactiae, a pathobiont responsible for invasive neonatal infections. We show that CovR binds to and represses a distal promoter of the cas operon, integrating immunity within the virulence regulatory network. The CovR-regulated promoter provides a controlled increase in off-target cleavages to counteract mutations in the target DNA, restores the potency of old immune memory, and stimulates the acquisition of new memory in response to recent infections. Regulation of Cas9 by CovR is conserved at the species level, with lineage specificities suggesting different adaptive trajectories. Altogether, we describe the coordinated regulation of immunity and virulence that enhances the bacterial immune repertoire during host-pathogen interaction.

Suggested Citation

  • Adeline Pastuszka & Maria-Vittoria Mazzuoli & Chiara Crestani & Léonie Deborde & Odile Sismeiro & Coralie Lemaire & Vanessa Rong & Myriam Gominet & Elise Jacquemet & Rachel Legendre & Philippe Lanotte, 2025. "The virulence regulator CovR boosts CRISPR-Cas9 immunity in Group B Streptococcus," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60871-6
    DOI: 10.1038/s41467-025-60871-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60871-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60871-6?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. Josiane E. Garneau & Marie-Ève Dupuis & Manuela Villion & Dennis A. Romero & Rodolphe Barrangou & Patrick Boyaval & Christophe Fremaux & Philippe Horvath & Alfonso H. Magadán & Sylvain Moineau, 2010. "The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA," Nature, Nature, vol. 468(7320), pages 67-71, November.
    2. Behrouz Eslami-Mossallam & Misha Klein & Constantijn V. D. Smagt & Koen V. D. Sanden & Stephen K. Jones & John A. Hawkins & Ilya J. Finkelstein & Martin Depken, 2022. "A kinetic model predicts SpCas9 activity, improves off-target classification, and reveals the physical basis of targeting fidelity," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Cosme Claverie & Francesco Coppolino & Maria-Vittoria Mazzuoli & Cécile Guyonnet & Elise Jacquemet & Rachel Legendre & Odile Sismeiro & Giuseppe Valerio Gaetano & Giuseppe Teti & Patrick Trieu-Cuot & , 2024. "Constitutive activation of two-component systems reveals regulatory network interactions in Streptococcus agalactiae," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Martin Pacesa & Luuk Loeff & Irma Querques & Lena M. Muckenfuss & Marta Sawicka & Martin Jinek, 2022. "R-loop formation and conformational activation mechanisms of Cas9," Nature, Nature, vol. 609(7925), pages 191-196, September.
    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. Gregory W. Goldberg & Manjunatha Kogenaru & Sarah Keegan & Max A. B. Haase & Larisa Kagermazova & Mauricio A. Arias & Kenenna Onyebeke & Samantha Adams & Daniel K. Beyer & David Fenyö & Marcus B. Noye, 2024. "Engineered transcription-associated Cas9 targeting in eukaryotic cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Matteo Ciciani & Michele Demozzi & Eleonora Pedrazzoli & Elisabetta Visentin & Laura Pezzè & Lorenzo Federico Signorini & Aitor Blanco-Miguez & Moreno Zolfo & Francesco Asnicar & Antonio Casini & Anna, 2022. "Automated identification of sequence-tailored Cas9 proteins using massive metagenomic data," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    3. Cécile Philippe & Carlee Morency & Pier-Luc Plante & Edwige Zufferey & Rodrigo Achigar & Denise M. Tremblay & Geneviève M. Rousseau & Adeline Goulet & Sylvain Moineau, 2022. "A truncated anti-CRISPR protein prevents spacer acquisition but not interference," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    4. Jianli Tao & Daniel E. Bauer & Roberto Chiarle, 2023. "Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Kuang Hu & Chia-Wei Chou & Claus O. Wilke & Ilya J. Finkelstein, 2024. "Distinct horizontal transfer mechanisms for type I and type V CRISPR-associated transposons," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Reina Nagamura & Tomoya Kujirai & Junko Kato & Yutaro Shuto & Tsukasa Kusakizako & Hisato Hirano & Masaki Endo & Seiichi Toki & Hiroaki Saika & Hitoshi Kurumizaka & Osamu Nureki, 2024. "Structural insights into how Cas9 targets nucleosomes," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    7. Marius Rutkauskas & Inga Songailiene & Patrick Irmisch & Felix E. Kemmerich & Tomas Sinkunas & Virginijus Siksnys & Ralf Seidel, 2022. "A quantitative model for the dynamics of target recognition and off-target rejection by the CRISPR-Cas Cascade complex," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    8. Yanan Liu & Lin Wang & Qian Zhang & Pengyu Fu & Lingling Zhang & Ying Yu & Heng Zhang & Hongtao Zhu, 2025. "Structural basis for RNA-guided DNA degradation by Cas5-HNH/Cascade complex," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    9. Qinchang Chen & Guohui Chuai & Haihang Zhang & Jin Tang & Liwen Duan & Huan Guan & Wenhui Li & Wannian Li & Jiaying Wen & Erwei Zuo & Qing Zhang & Qi Liu, 2023. "Genome-wide CRISPR off-target prediction and optimization using RNA-DNA interaction fingerprints," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Pierre Aldag & Marius Rutkauskas & Julene Madariaga-Marcos & Inga Songailiene & Tomas Sinkunas & Felix Kemmerich & Dominik Kauert & Virginijus Siksnys & Ralf Seidel, 2023. "Dynamic interplay between target search and recognition for a Type I CRISPR-Cas system," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Xieshuting Deng & Wei Sun & Xueyan Li & Jiuyu Wang & Zhi Cheng & Gang Sheng & Yanli Wang, 2024. "An anti-CRISPR that represses its own transcription while blocking Cas9-target DNA binding," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Eman A. Ageely & Ramadevi Chilamkurthy & Sunit Jana & Leonora Abdullahu & Daniel O’Reilly & Philip J. Jensik & Masad J. Damha & Keith T. Gagnon, 2021. "Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    13. Xuan Zou & Xiaohong Xiao & Ziran Mo & Yashi Ge & Xing Jiang & Ruolin Huang & Mengxue Li & Zixin Deng & Shi Chen & Lianrong Wang & Sang Yup Lee, 2022. "Systematic strategies for developing phage resistant Escherichia coli strains," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. Ugo Rogo & Ambra Viviani & Claudio Pugliesi & Marco Fambrini & Gabriele Usai & Marco Castellacci & Samuel Simoni, 2025. "Improving Crop Tolerance to Abiotic Stress for Sustainable Agriculture: Progress in Manipulating Ascorbic Acid Metabolism via Genome Editing," Sustainability, MDPI, vol. 17(2), pages 1-32, January.

    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:16:y:2025:i:1:d:10.1038_s41467-025-60871-6. 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.