Diverse bacterial pattern recognition receptors sense the conserved phage proteome

Area of Science:

• Microbiology
• Structural Biology
• Immunology

Background:

• Cellular immunity relies on recognizing foreign molecules.
• Prokaryotic STAND NTPases are vital for sensing phage proteins, but their diversity is understudied.
• Eukaryotic nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are part of the STAND NTPase superfamily.

Purpose of the Study:

• To systematically analyze prokaryotic STAND NTPases for antiviral defense.
• To identify novel families and their specific phage protein targets.
• To elucidate the structural mechanisms of phage recognition by bacterial immune systems.

Main Methods:

• Systematic phylogenetic analysis of prokaryotic STAND NTPases.
• Cryo-electron microscopy (cryo-EM) to determine protein structures.
• High-throughput genetic screens to identify protein interactions and functions.

Main Results:

• Identified at least 90 distinct STAND NTPase families involved in antiviral defense.
• The Avs7 family recognizes the major capsid protein (MCP) of tailed phages, with cryo-EM structures revealing its assembly mechanism with EF-Tu.
• 13 additional STAND families were found to target 12 conserved phage protein folds, including MCP, portal, and DNA replication proteins.

Conclusions:

• Prokaryotic immunity employs a vast array of STAND NTPases for recognizing diverse phage components.
• Structure-based pattern recognition and host factor repurposing are key strategies in bacterial antiviral defense.
• This work expands the known repertoire of bacterial immune sensors and their targets, offering insights into phage-bacteria coevolution.