A modular effector with a DNase domain and a marker for T6SS substrates

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Bacteria utilize type VI secretion systems (T6SSs) to deliver toxic effectors for interbacterial competition.
• The identities and functions of many T6SS effectors remain largely unknown, hindering our understanding of bacterial warfare.

Purpose of the Study:

• To identify and characterize novel antibacterial effectors delivered by T6SSs.
• To investigate the structure, function, and evolutionary context of newly discovered toxin domains and associated domains.

Main Methods:

• Bioinformatic analysis to identify novel toxin domains and associated protein domains.
• Biochemical assays to determine the nuclease activity of the identified effector.
• Genetic and functional studies to assess the role of the effector and its associated domains in T6SS-mediated toxicity.

Main Results:

• Identification of a novel, widespread DNase toxin domain, termed Polymorphic Nuclease effector (PoNe), within a Vibrio T6SS effector.
• PoNe belongs to the PD-(D/E)xK phosphodiesterase superfamily and is associated with multiple secretion systems (T5, T6, T7).
• Discovery of a linked domain of unknown function (FIX domain) that aids in identifying T6SS effector candidates with novel toxins.

Conclusions:

• The study reveals PoNe as a potent antibacterial DNase effector and highlights the modular assembly of bacterial toxins.
• The FIX domain serves as a valuable marker for discovering new T6SS effectors and their associated toxin domains.
• Findings advance the understanding of bacterial secretion systems and the evolution of bacterial toxins.