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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 Goncalves ; 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
Total Authors: 11
Document type: Journal article
Source: eLIFE; v. 11, p. 26-pg., 2022-10-13.
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. (AU)

FAPESP's process: 17/17303-7 - Structure and function of bacterial secretion systems
Grantee:Shaker Chuck Farah
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 19/12234-2 - Isolation and structural studies on the Xanthomonas citri Type IV pilus and T4SS pilus
Grantee:Edgar Enrique Llontop Cornejo
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 21/03400-6 - Development of a universal pipeline for genomic context analysis from different sources of data.
Grantee:Gianlucca Gonçalves Nicastro
Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 16/09047-8 - Comparative genomics of bacterial toxins associated with type IV secretion systems
Grantee:Robson Francisco de Souza
Support Opportunities: Regular Research Grants
FAPESP's process: 20/15389-4 - Cloning and antibacterial activity of novel Salmonella T6SS effectors
Grantee:Gustavo Chagas Santos
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/25316-4 - Function of SPI-6 T6SS and SPI-19 T6SS of Salmonella during competition with the gut microbiota
Grantee:Julia Takuno Hespanhol
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/04553-8 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells
Grantee:Ethel Bayer Santos
Support Opportunities: Scholarships in Brazil - Young Researchers
FAPESP's process: 17/02178-2 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells
Grantee:Ethel Bayer Santos
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 19/22715-8 - Function of Salmonella bongori SPI-22 T6SS in bacterial competitions and interactions with phagocytic host cells
Grantee:Daniel Enrique Sánchez Limache
Support Opportunities: Scholarships in Brazil - Master