DISARM is a widespread bacterial defence system with broad anti-phage activities

  • Nature Microbiologyvolume 3pages9098 (2018)
  • doi:10.1038/s41564-017-0051-0
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The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction–modification and CRISPR–Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction–modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction–modification systems. Our results suggest that DISARM is a new type of multi-gene restriction–modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.

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The authors thank M. Shamir, G. Amitai, S. Edelheit, A. Lopatina, T. Wein, Z. Erez and Z. Meir for discussions during the course of this study. The authors also thank A. Leavitt for discussions and assistance in adsorption assays and M. Keren for assistance with plaque assays. The authors thank I. Kolodkin-Gal for the pDR110 plasmid, J.M. Peters for the pJMP4 plasmid, S. Ben-Yehuda for the ET3 strain, P. Tavares for the lacO-containing SPP1 phage strain, T. Bucher, I. Pereman and E. Tzipilevich for their assistance with microscopy and O. Golani from the Weizmann Life Sciences Core Facilities for assistance in image analyses. This study was supported, in part, by the Israel Science Foundation (personal grants 1303/12 and 1360/16 and I-CORE grant 1796/12), the European Research Council (grant ERC-CoG 681203), the Minerva Foundation and by a research grant from the David and Fela Shapell Family Foundation.

Author information

Author notes

  1. Gal Ofir and Sarah Melamed contributed equally to this work.


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

    • Gal Ofir
    • , Sarah Melamed
    • , Hila Sberro
    • , Shahar Silverman
    • , Gilad Yaakov
    • , Shany Doron
    •  & Rotem Sorek
  2. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel

    • Zohar Mukamel
  3. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

    • Zohar Mukamel
  4. Departments of Medicine and Genetics, Stanford University, Stanford, CA, USA

    • Hila Sberro


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G.O. and S.M. designed the experiments, performed the experiments and analysed the results. H.S. identified, bioinformatically, the DISARM system. S.D. and G.O. performed bioinformatics analysis of DISARM systems. Z.M. performed bisulfite sequencing. S.S. assisted with experiments. G.Y. and G.O. performed microscopy experiments. G.O. and R.S. wrote the manuscript. R.S. supervised the study.

Competing interests

R.S. is a scientific founder of BiomX and a member of its scientific advisory board.

Corresponding author

Correspondence to Rotem Sorek.

Electronic supplementary material

  1. Supplementary Information

    Supplementary Table 3, Supplementary Figures 1–10

  2. Life Sciences Reporting Summary

  3. Supplementary Table 1

    Genes containing DUF1998, with no other domain, in microbial genomes

  4. Supplementary Table 2

    DISARM systems detected in microbial genomes