Article | Published:

Communication between viruses guides lysis–lysogeny decisions

Nature volume 541, pages 488493 (26 January 2017) | Download Citation

Abstract

Temperate viruses can become dormant in their host cells, a process called lysogeny. In every infection, such viruses decide between the lytic and the lysogenic cycles, that is, whether to replicate and lyse their host or to lysogenize and keep the host viable. Here we show that viruses (phages) of the SPbeta group use a small-molecule communication system to coordinate lysis–lysogeny decisions. During infection of its Bacillus host cell, the phage produces a six amino-acids-long communication peptide that is released into the medium. In subsequent infections, progeny phages measure the concentration of this peptide and lysogenize if the concentration is sufficiently high. We found that different phages encode different versions of the communication peptide, demonstrating a phage-specific peptide communication code for lysogeny decisions. We term this communication system the ‘arbitrium’ system, and further show that it is encoded by three phage genes: aimP, which produces the peptide; aimR, the intracellular peptide receptor; and aimX, a negative regulator of lysogeny. The arbitrium system enables a descendant phage to ‘communicate’ with its predecessors, that is, to estimate the amount of recent previous infections and hence decide whether to employ the lytic or lysogenic cycle.

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Acknowledgements

We thank J. Peters and C. Gross for sharing the Bacillus dCas9 system; A. Eldar for the oppD mutant and for advice on quorum sensing systems in Bacilli; I. Kolodkin-Gal for the 3610 strain; Y. Levin from the de Botton Institute for Protein Profiling for assistance in mass spectrometry; D. Fass and G. Armoni for advice regarding protein structure; and H. Sharir for assistance in the microscale thermophoresis analysis. We also thank D. Pollack, I. Kolodkin-Gal, O. Dym and T. Unger for support and discussion throughout the study. R.S. was supported, in part, by the Israel Science Foundation (personal grants 1303/12, 1360/16 and I-CORE grant 1796/12), the European Research Council (ERC) (grants ERC-StG 260432 and ERC-CoG 681203), Human Frontier Science Program (HFSP grant RGP0011/2013), the Abisch-Frenkel foundation, the Pasteur-Weizmann council grant, the Minerva Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, and by a Deutsch-Israelische Projektkooperation (DIP) grant from the DFG. The ISPC is supported by the Dana and Yossie Holander Center for Structural Proteomics.

Author information

Author notes

    • Zohar Erez
    •  & Ida Steinberger-Levy

    These authors contributed equally to this work.

Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel

    • Zohar Erez
    • , Ida Steinberger-Levy
    • , Maya Shamir
    • , Shany Doron
    • , Avigail Stokar-Avihail
    • , Sarah Melamed
    • , Azita Leavitt
    • , Gil Amitai
    •  & Rotem Sorek
  2. Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel

    • Ida Steinberger-Levy
  3. Israel Structural Proteomics Center (ISPC), Faculty of Biochemistry, Weizmann Institute of Science, Rehovot 7610001, Israel

    • Yoav Peleg
    •  & Shira Albeck
  4. de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel

    • Alon Savidor

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Contributions

Z.E. directly performed or was involved in all experiments unless otherwise stated. I.S.L. performed conditioned media and proteinase K assays. S.D. annotated phi3T genome. A.S. analysed the mass spectrometry results. Y.P. and S.A. expressed and purified AimR–6×His. A.S.A., A.L. and S.M. constructed strains. G.A. performed microscale thermophoresis, crosslinking and ChIP–seq experiments. M.S. performed RNA-seq experiments. R.S. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Gil Amitai or Rotem Sorek.

Reviewer Information Nature thanks P. Fineran and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Extended data

Supplementary information

Excel files

  1. 1.

    Supplementary Table 1

    This file shows the Homologs of AimR-AimP in sequenced genomes. Positions of AimR homologs are provided, as well as the corresponding full pro-pre-peptide sequence and the mature peptide sequences.

  2. 2.

    Supplementary Table 2

    This file contains the annotation of the phi3T genome.

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DOI

https://doi.org/10.1038/nature21049

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