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Cited by 45Bacterial Genetics and BiotechnologyEscherichia coli research studiesSalmonella and Campylobacter epidemiology

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Antibacterial T6SS effectors with a VRR-Nuc domain are structure-specific nucleases

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Hespanhol, Julia Takuno, Sanchez-Limache, Daniel Enrique, Nicastro, Gianlucca Gonçalves, Mead, Liam, Llontop, Edgar Enrique, Chagas-Santos, Gustavo, Farah, Chuck Shaker, de Souza, Robson Francisco, Galhardo, Rodrigo da Silva, Lovering, Andrew L, Bayer-Santos, Ethel·2022·eLife
DOI 10.7554/elife.82437PMC PMC9635880

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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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Metadata

Authors
Hespanhol, J. T., Sanchez-Limache, D. E., Nicastro, G. G., Mead, L., Llontop, E. E., Chagas-Santos, G., Farah, C. S., de Souza, R. F., Galhardo, R. D. S., Lovering, A. L., & Bayer-Santos, E.
Affiliations
  • Universidade de São Paulo (BR)
  • Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo
  • Harvard University (US)
  • University of Birmingham (GB)
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-10-13
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.82437
PMC
PMC9635880
OpenAlex
W4304943972
Cited by
45
References
3
Citations by year
2026: 14 · 2025: 6 · 2024: 12 · 2023: 10 · 2022: 3
FWCI
4.67
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
Funders
  • Sao Paulo Research Foundation (2016/09047-8, 2017/17303-7, 2017/02178-2)
  • Wellcome Trust (209437/Z/17/Z)
  • FAPESP Fellowship (2018/25316-4, 2019/22715-8, 2021/03400-6, 2019/12234-2, 2020/15389-4, 2018/04553-8)
  • MIBTP Studentship
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
Keywords
type VI secretion system, T6SS effectors, structure-specific nucleases, Salmonella bongori, DNA double-strand breaks, SOS response, bacterial competition, pathogenicity islands, toxin evolution, DNA repair enzymes, crystal structure
MeSH terms
Type VI Secretion Systems, Anti-Bacterial Agents, Bacterial Proteins, Endonucleases, Escherichia coli, Phylogeny, Genomic Islands

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