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The ClpX protease is essential for inactivating the CI master repressor and completing prophage induction in Staphylococcus aureus

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  • Mohammed A. Thabet

    (University of Glasgow
    Al-Baha University)

  • José R. Penadés

    (Imperial College London)

  • Andreas F. Haag

    (University of Glasgow
    University of St Andrews, North Haugh)

Abstract

Bacteriophages (phages) are the most abundant biological entities on Earth, exerting a significant influence on the dissemination of bacterial virulence, pathogenicity, and antimicrobial resistance. Temperate phages integrate into the bacterial chromosome in a dormant state through intricate regulatory mechanisms. These mechanisms repress lytic genes while facilitating the expression of integrase and the CI master repressor. Upon bacterial SOS response activation, the CI repressor undergoes auto-cleavage, producing two fragments with the N-terminal domain (NTD) retaining significant DNA-binding ability. The process of relieving CI NTD repression, essential for prophage induction, remains unknown. Here we show a specific interaction between the ClpX protease and CI NTD repressor fragment of phages Ф11 and 80α in Staphylococcus aureus. This interaction is necessary and sufficient for prophage activation after SOS-mediated CI auto-cleavage, defining the final stage in the prophage induction cascade. Our findings unveil unexpected roles of bacterial protease ClpX in phage biology.

Suggested Citation

  • Mohammed A. Thabet & José R. Penadés & Andreas F. Haag, 2023. "The ClpX protease is essential for inactivating the CI master repressor and completing prophage induction in Staphylococcus aureus," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42413-0
    DOI: 10.1038/s41467-023-42413-0
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    References listed on IDEAS

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    1. Adrianna P. P. Zhang & Ying Z. Pigli & Phoebe A. Rice, 2010. "Structure of the LexA–DNA complex and implications for SOS box measurement," Nature, Nature, vol. 466(7308), pages 883-886, August.
    2. María Ángeles Tormo-Más & Ignacio Mir & Archana Shrestha & Sandra M. Tallent & Susana Campoy & Íñigo Lasa & Jordi Barbé & Richard P. Novick & Gail E. Christie & José R. Penadés, 2010. "Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands," Nature, Nature, vol. 465(7299), pages 779-782, June.
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