Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases
- Universidade de São Paulo, Brazil
- University of Birmingham, United Kingdom
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.
Data availability
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
Daniel Enrique Sanchez-Limache
Edgar Enrique Llontop
Robson Francisco de Souza
Rodrigo da Silva Galhardo
Ethel Bayer-Santos
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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Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases
eLife 11:e82437.
https://doi.org/10.7554/eLife.82437
