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

Nature Microbiology volume 3, pages 1285–1294 (2018)Cite this article

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Abstract

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.

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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.

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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.

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Acknowledgements

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.

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Author notes

  1. These authors contributed equally: Chao Dou, Jie Xiong, Yijun Gu.

Authors and Affiliations

  1. Division of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China

    Chao Dou, Jie Xiong, Jinjing Wang, Yuehong Hu, Dan Zhou, Xianghui Fu, Shiqian Qi, Xiaofeng Zhu, Shaohua Yao, Heng Xu, Chunlai Nie, Zongan Liang, Shengyong Yang, Yuquan Wei & Wei Cheng

  2. Shanghai Synchrotron Radiation Facility, Zhangjiang Lab, Shanghai, China

    Yijun Gu

  3. Shandong Academy of Medical Sciences, Shandong Institute of Parasitic Disease, Jining, China

    Kun Yin

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Contributions

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.

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Correspondence to Wei Cheng.

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Supplementary Figures 1–11, Supplementary Table 1.

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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). https://doi.org/10.1038/s41564-018-0259-7

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