Type VII Toxin/Antitoxin Classification System for Antitoxins that Enzymatically Neutralize Toxins

Area of Science:

• Microbiology and Molecular Biology
• Biochemistry and Enzymology

Background:

• Toxin/antitoxin (TA) systems are ubiquitous in bacteria and archaea, regulating growth via toxin-antidote interactions.
• Existing TA systems are classified into six classes based on antitoxin nature and toxin inactivation mechanisms.

Purpose of the Study:

• To identify and characterize novel TA systems with enzymatic antitoxins.
• To propose a new classification framework for TA systems based on enzymatic modification.

Main Methods:

• Identification of TA systems where the antitoxin is an enzyme directly targeting the toxin.
• Biochemical analysis of three distinct systems: Hha/TomB, TglT/TakA, and HepT/MntA.

Main Results:

• Discovery of three new TA systems (Hha/TomB, TglT/TakA, HepT/MntA) where enzyme antitoxins chemically modify their cognate toxins.
• Demonstration of enzymatic inactivation mechanisms: oxidation, phosphorylation, and AMPylation.

Conclusions:

• Proposal of a new 'Type VII TA system' classification for systems utilizing enzyme antitoxins that post-translationally modify toxins.
• This classification will enhance the understanding and categorization of diverse TA system biochemical functions and aid future discoveries.