Abstract

The type VI secretion system (T6SS) secretes antibacterial effectors into target competitors. Salmonella spp. encode five phylogenetically distinct T6SSs. Here we characterize the function of the SPI-22 T6SS of Salmonella bongori showing that it has antibacterial activity and identify a group of antibacterial T6SS effectors (TseV1-4) containing an N-terminal PAAR-like domain and a C-terminal VRR-Nuc domain encoded next to cognate immunity proteins with a DUF3396 domain (TsiV1-4). TseV2 and TseV3 are toxic when expressed in Escherichia coli and bacterial competition assays confirm that TseV2 and TseV3 are secreted by the SPI-22 T6SS. Phylogenetic analysis reveals that TseV1-4 are evolutionarily related to enzymes involved in DNA repair. TseV3 recognizes specific DNA structures and preferentially cleave splayed arms, generating DNA double-strand breaks and inducing the SOS response in target cells. The crystal structure of the TseV3:TsiV3 complex reveals that the immunity protein likely blocks the effector interaction with the DNA substrate. These results expand our knowledge on the function of Salmonella pathogenicity islands, the evolution of toxins used in biological conflicts, and the endogenous mechanisms regulating the activity of these toxins.

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All data generated during this study are included in the manuscript and supporting files. Source data files have been provided.

Article and author information

Author details

  1. Julia Takuno Hespanhol

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Enrique Sanchez-Limache

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1364-7527
  3. Gianlucca Gonçalves Nicastro

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Liam Mead

    Department of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Edgar Enrique Llontop

    Departamento de Bioquímica, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4910-9667
  6. Gustavo Chagas-Santos

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  7. Chuck Shaker Farah

    Departamento de Bioquímica, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  8. Robson Francisco de Souza

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5284-4630
  9. Rodrigo da Silva Galhardo

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5686-9704
  10. Andrew Lovering

    Department of Biosciences, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Ethel Bayer-Santos

    Departamento de Microbiologia, Universidade de São Paulo, Sao Paulo, Brazil
    For correspondence
    ebayersantos@usp.br
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3832-3449

Funding

Sao Paulo Research foundation (2016/09047-8)

  • Robson Francisco de Souza

FAPESP Fellowship (2018/04553-8)

  • Ethel Bayer-Santos

MIBTP Studentship

  • Liam Mead

Sao Paulo Research Foundation (2017/17303-7)

  • Chuck Shaker Farah

Sao Paulo Research Foundation (2017/02178-2)

  • Ethel Bayer-Santos

Welcome Trust (209437/Z/17/Z)

  • Andrew Lovering

FAPESP Fellowship (2018/25316-4)

  • Julia Takuno Hespanhol

FAPESP Fellowship (2019/22715-8)

  • Daniel Enrique Sanchez-Limache

FAPESP Fellowship (2021/03400-6)

  • Gianlucca Gonçalves Nicastro

FAPESP Fellowship (2019/12234-2)

  • Edgar Enrique Llontop

FAPESP Fellowship (2020/15389-4)

  • Gustavo Chagas-Santos

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Hespanhol et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Julia Takuno Hespanhol
  2. Daniel Enrique Sanchez-Limache
  3. Gianlucca Gonçalves Nicastro
  4. Liam Mead
  5. Edgar Enrique Llontop
  6. Gustavo Chagas-Santos
  7. Chuck Shaker Farah
  8. Robson Francisco de Souza
  9. Rodrigo da Silva Galhardo
  10. Andrew Lovering
  11. Ethel Bayer-Santos
(2022)
Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases
eLife 11:e82437.
https://doi.org/10.7554/eLife.82437

Share this article

https://doi.org/10.7554/eLife.82437

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