Structural and functional insights into the regulation of the lysis–lysogeny decision in viral communities


Communication is vital for all organisms including microorganisms, which is clearly demonstrated by the bacterial quorum-sensing system. However, the molecular mechanisms underlying communication among viruses (phages) via the quorum-sensing-like ‘arbitrium’ system remain unclear. Viral or host densities are known to be related to an increased prevalence of lysogeny; however, how the switch from the lytic to the lysogenic pathway occurs is unknown. Thus, we sought to reveal mechanisms of communication among viruses and determine the lysogenic dynamics involved. Structural and functional analyses of the phage-derived SAIRGA and GMPRGA peptides and their corresponding receptors, phAimR and spAimR, indicated that SAIRGA directs the lysis–lysogeny decision of phi3T by modulating conformational changes in phAimR, whereas GMPRGA regulates the lysis–lysogeny pathway by stabilizing spAimR in the dimeric state. Although temperate viruses are thought to share a similar lytic–lysogenic cycle switch model, our study suggests the existence of alternative strain-specific mechanisms that regulate the lysis–lysogeny decision. Collectively, these findings provide insights into the molecular mechanisms underlying communication among viruses, offering theoretical applications for the treatment of infectious viral diseases.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Lysis–lysogeny induced by exogenous synthesized peptides.
Fig. 2: Peptides can modulate AimR receptors.
Fig. 3: Structures of phAimR and spAimR.
Fig. 4: Structural basis for peptide recognition.
Fig. 5: Structural comparisons and gel-filtration analysis.
Fig. 6: Mechanistic model of the arbitrium system.

Data availability

The coordinates of the structures have been deposited in the Protein Data Bank (PDB) under the accession codes 5ZVV for SeMet-phAimR, 5ZVW for ligand-bound.phAimR, 5ZW5 for SeMet-spAimR and 5ZW6 for ligand-bound.spAimR. Other data that support the findings of this study are available from the corresponding author upon request.


  1. 1.

    Whiteley, M., Diggle, S. P. & Greenberg, E. P. Progress in and promise of bacterial quorum sensing research. Nature 551, 313–320 (2017).

    CAS  Article  Google Scholar 

  2. 2.

    Kai, P. & Bassler, B. Quorum sensing signal-response systems in Gram-negative bacteria. Nat. Rev. Microbiol. 14, 576–588 (2016).

    Article  Google Scholar 

  3. 3.

    Schuster, M., Sexton, D. J., Diggle, S. P. & Greenberg, E. P. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu. Rev. Microbiol. 67, 43–63 (2013).

    CAS  Article  Google Scholar 

  4. 4.

    Greenberg, E. P., Hastings, J. W. & Ulitzur, S. Induction of luciferase synthesis in Beneckea harveyi by other marine bacteria. Arch. Microbiol. 120, 87–91 (1979).

    CAS  Article  Google Scholar 

  5. 5.

    Engebrecht, J., Nealson, K. & Silverman, M. Bacterial bioluminescence: isolation and genetic analysis of functions from Vibrio fischeri. Cell 32, 773–781 (1983).

    CAS  Article  Google Scholar 

  6. 6.

    Engebrecht, J. & Silverman, M. Identification of genes and gene products necessary for bacterial bioluminescence. Proc. Natl Acad. Sci. USA 81, 4154–4158 (1984).

    CAS  Article  Google Scholar 

  7. 7.

    Havarstein, L. S., Coomaraswamy, G. & Morrison, D. A. An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proc. Natl Acad. Sci. USA 92, 11140–11144 (1995).

    CAS  Article  Google Scholar 

  8. 8.

    Ji, G., Beavis, R. C. & Novick, R. P. Cell density control of staphylococcal virulence mediated by an octapeptide pheromone. Proc. Natl Acad. Sci. USA 92, 12055–12059 (1995).

    CAS  Article  Google Scholar 

  9. 9.

    Hornby, J. M. et al. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl. Environ. Microbiol. 67, 2982–2992 (2001).

    CAS  Article  Google Scholar 

  10. 10.

    Kügler, S., Sebghati, T. S., Eissenberg, L. G. & Goldman, W. E. Phenotypic variation and intracellular parasitism by Histoplasma capsulatum. Proc. Natl Acad. Sci. USA 97, 8794–8798 (2000).

    Article  Google Scholar 

  11. 11.

    Ptashne, M. A Genetic Switch: Phage λ and Higher Organisms (Blackwell Scientific Inc., Hoboken, 1992).

  12. 12.

    Dargent, D., Mathevet, P. & Mellier, G. Genetic switch: phage lambda revisited. RöFo 135, 649–652 (2004).

    Google Scholar 

  13. 13.

    Golding, I. Single-cell studies of phage λ: hidden treasures under occam’s rug. Annu. Rev. Virol. 3, 453–472 (2016).

    CAS  Article  Google Scholar 

  14. 14.

    Schultz, D., Wolynes, P. G., Ben, J. E. & Onuchic, J. N. Deciding fate in adverse times: sporulation and competence in Bacillus subtilis. Proc. Natl Acad. Sci. USA 106, 21027–21034 (2009).

    CAS  Article  Google Scholar 

  15. 15.

    Erez, Z. et al. Communication between viruses guides lysis–lysogeny decisions. Nature 541, 488–493 (2017).

    CAS  Article  Google Scholar 

  16. 16.

    Hynes, A. P. & Moineau, S. Phagebook: the social network. Mol. Cell 65, 963–964 (2017).

    CAS  Article  Google Scholar 

  17. 17.

    Davidson, A. R. Virology: phages make a group decision. Nature 541, 466–467 (2017).

    CAS  Article  Google Scholar 

  18. 18.

    Novick, R. P. & Geisinger, E. Quorum sensing in staphylococci. Annu. Rev. Genet. 42, 541–564 (2008).

    CAS  Article  Google Scholar 

  19. 19.

    Ng, W. L. & Bassler, B. L. Bacterial quorum-sensing network architectures. Annu. Rev. Genet. 43, 197–222 (2009).

    CAS  Article  Google Scholar 

  20. 20.

    Kai, P. & Vogel, J. Regulatory RNA in bacterial pathogens. Cell Host Microbe 8, 116–127 (2010).

    Article  Google Scholar 

  21. 21.

    Grote, J., Krysciak, D. & Streit, W. R. Phenotypic heterogeneity, a phenomenon that may explain why quorum sensing does not always result in truly homogenous cell behavior. Appl. Environ. Microbiol. 81, 5280–5289 (2015).

    CAS  Article  Google Scholar 

  22. 22.

    Cárcamooyarce, G., Lumjiaktase, P., Kümmerli, R. & Eberl, L. Quorum sensing triggers the stochastic escape of individual cells from Pseudomonas putida biofilms. Nat. Commun. 6, 5945 (2015).

    Article  Google Scholar 

  23. 23.

    Gallego, F. D. S. & Marina, A. Structural basis of Rap phosphatase inhibition by Phr peptides. PLoS Biol. 11, e1001511 (2013).

    Article  Google Scholar 

  24. 24.

    Jiang, S. C. & Paul, J. H. Significance of lysogeny in the marine environment: studies with isolates and a model of lysogenic phage production. Microb. Ecol. 35, 235–243 (1998).

    CAS  Article  Google Scholar 

  25. 25.

    Vage, S., Storesund, J. E., Giske, J. & Thingstad, T. F. Optimal defense strategies in an idealized microbial food web under trade-off between competition and defense. PLoS ONE 9, e101415 (2014).

  26. 26.

    Knowles, B. et al. Lytic to temperate switching of viral communities. Nature 531, 466–470 (2016).

    CAS  Article  Google Scholar 

  27. 27.

    Weitz, J. S., Beckett, S. J., Brum, J. R., Cael, B. B. & Dushoff, J. Lysis, lysogeny and virus–microbe ratios. Nature 549, E1–E3 (2016).

    Article  Google Scholar 

  28. 28.

    Silveira, C. B. & Rohwer, F. L. Piggyback-the-Winner in host-associated microbial communities. NPJ Biofilms Microbiomes 2, 16010 (2016).

    Article  Google Scholar 

  29. 29.

    Larson, M. H. et al. CRISPR interference (CRISPRi) for sequence-specific control of geneexpression. Nat. Protoc. 8, 2180–2196 (2013).

    CAS  Article  Google Scholar 

  30. 30.

    Peters, J. M. et al. A comprehensive, CRISPR-based functional analysis of essential genes in bacteria. Cell 165, 1493–1506 (2016).

    CAS  Article  Google Scholar 

  31. 31.

    Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. 66, 486–501 (2010).

    CAS  Google Scholar 

  32. 32.

    Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. 68, 352–367 (2012).

    CAS  Article  Google Scholar 

  33. 33.

    Carlson, K. in Bacteriophages, Biology and Applications (eds Kutter, E. & Sulakvelidze, A.) 437–494 (CRC Press, Boca Raton, 2005).

  34. 34.

    Larkin, M. et al. Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947–2948 (2007).

    CAS  Article  Google Scholar 

Download references


We thank the staff of the BL17U1 beamline and BL19U1 at the Shanghai Synchrotron Radiation Facility, Zhangjiang Lab, for assistance during data collection. We thank S. Fan from Tsinghua University for data collection. This work was funded by a grant to W.C. from National Key Research and Development Program of China (2018YFC1002802), and the National Natural Science Foundation of China (grants no. 31570842 and no. 31870836), awards from the National Young Thousand Talents Program and the Sichuan Province Thousand Talents programme in China.

Author information




W.C. designed the research. C.D., J.X., D.Z. and J.W. made the constructs. C.D., J.X. and Y.H. purified the proteins. C.D., J.X. and K.Y. performed the ITC and activity assays, and grew and optimized the crystals. C.D. and Y.G. collected the data. Y.G., X.Z. and W.C. determined the structure. C.D., X.F., S.Q., S.Yao, H.Z., C.N., Z.L., S.Yang and Y.W. contributed materials and data analysis. W.C. wrote manuscript with contributions from the other authors.

Corresponding author

Correspondence to Wei Cheng.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Supplementary Information

Supplementary Figures 1–11, Supplementary Table 1.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dou, C., Xiong, J., Gu, Y. et al. Structural and functional insights into the regulation of the lysis–lysogeny decision in viral communities. Nat Microbiol 3, 1285–1294 (2018).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing