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

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• The type VI secretion system (T6SS) is a key virulence factor in many Gram-negative bacteria, mediating interbacterial antagonism.
• Salmonella species possess multiple T6SS gene clusters, suggesting diverse functional roles.

Purpose of the Study:

• To characterize the function of the SPI-22 T6SS in Salmonella bongori.
• To identify and functionally analyze the cognate antibacterial effectors and immunity proteins.

Main Methods:

• Bacterial competition assays
• Genetic manipulation of Salmonella bongori and Escherichia coli
• Phylogenetic analysis
• Crystal structure determination of TseV3:TsiV3 complex

Main Results:

• The SPI-22 T6SS of S. bongori demonstrates antibacterial activity.
• Four novel T6SS effectors (TseV1-4) with DNAse activity were identified, along with cognate immunity proteins (TsiV1-4).
• TseV3 specifically cleaves splayed DNA arms, inducing the SOS response and DNA double-strand breaks in target cells.

Conclusions:

• The SPI-22 T6SS contributes to interbacterial competition in S. bongori.
• TseV effectors represent a novel class of antibacterial toxins involved in DNA repair and damage.
• The TsiV immunity proteins neutralize effector activity by blocking DNA substrate interaction.