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

• DOI: 10.7554/elife.82437
• Publication Date: 2022-10-13T12:00:39Z
• Authors: Julia Takuno Hesp...; Daniel Enrique Sa...; Gianlucca Gonçalv...; Liam Mead; Edgar Enrique Llo...; Gustavo Chagas-Sa...; Chuck Shaker Farah; Robson Francisco ...; Rodrigo da Silva ...; Andrew L Lovering; Ethel Bayer-Santos
• Keywords: Microbiology and Infectious Disease; 0303 health sciences; Genomic Islands; QH301-705.5; Science; Q; R; Type VI Secretion Systems; VRR-Nuc; Endonucleases; Anti-Bacterial Agents; 03 medical and health sciences; T6SS; effector; Bacterial Proteins; Salmonella; Escherichia coli; Medicine; nuclease; Biology (General); toxin; Phylogeny

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