Structural and functional diversity of toxin-antitoxin-chaperone systems

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Toxin-antitoxin-chaperone (TAC) systems are three-part gene clusters.
• These systems encode a toxin, antitoxin, and a specialized SecB-like chaperone (SecB^TA).
• Emerging roles in phage defense have been identified for TAC systems.

Purpose of the Study:

• To identify and classify SecB homologs and associated TACs across bacteria.
• To understand the evolutionary relationships and diversity of TAC systems.

Main Methods:

• Surveyed the full RefSeq database for SecB homologs and TACs.
• Utilized phylogenetic and gene neighborhood analyses.
• Performed structural predictions and toxin activity assays.

Main Results:

• Identified three major SecB subfamilies, including a diverse SecB^TA clade.
• Discovered eight TAC classes, five previously unknown.
• Showed conserved structural interfaces and incongruent SecB chaperone phylogeny, suggesting modular evolution.
• Demonstrated toxicity of class 2 ART toxins, inhibiting protein synthesis.
• Found all TAC classes can be prophage encoded.

Conclusions:

• SecB^TA chaperones are diverse and associated with multiple TAC classes.
• Modular shuffling of TA components and SecB chaperones drives TAC evolution.
• Prophage encoding facilitates TAC mobility and diversification, highlighting their role in phage-bacteria interactions.