Contributors: Marian Dominguez-Mirazo


Pore-forming proteins called gasdermins control cell-death response to infection in animals. Gasdermins are also present in bacteria where they have been shown to act as an abortive infection system that permeabilizes the cell membrane before phage release (, ) . In Lysobacter, the gasdermin operon includes two genes encoding trypsin-like protease domains, and a gene encoding an ATPase domain () . Intact active sites for the second protease and the ATPase, but not the first protease, are required for successful phage defense () . The domain architecture of the ATPase suggests it belongs to a protein family that is considered the ancestor of the eukaryotic nucleotide oligomerization domain (NOD)-like receptor (NLR) protein family () . In animals, NLR initiates the formation of the inflammasome complex () . The second protease contains a region with a similar structure to the human CARD domain () . The CARD domain takes part in the assembly of immune protein complexes () . The CARD-like domain in the Lysobacter system is required for successful phage defense () . Homology searches recovered multiple bacterial operons that include two proteases, one of them containing a CARD-like domain, and an NLR-like protein. In most cases, the effector gasdermin gene was replaced by another gene:ref{doi=10.1101/2023.05.28.542683}. The operon found in Pedobacter rhizosphaerae exhibits phage defense capabilities and contains a protein with phospholipase and endonuclease domains replacing the gasdermin gene. This system confers protection against the same phages as the Lysobacter gasdermin-containing system, suggesting that the proteases and ATPase participate in phage specificity and recognition.

Molecular mechanisms

For the Lysobacter system, the effector has been described as a pore-formin protein that disrupts the cell membrane () . To our knowledge, other parts of the molecular mechanisms have yet to be elucidated.

Example of genomic structure

A total of 5 subsystems have been described for the CARD_NLR system.

Here is some examples found in the RefSeq database:

The CARD_NLR_Endonuclease system in Spirosoma montaniterrae (GCF_001988955.1, NZ_CP014263) is composed of 4 proteins Trypsin (WP_077131797.1) CARD_Protease_new (WP_077131798.1) NLR_new (WP_157579217.1) Endonuclease (WP_083732853.1)

The CARD_NLR_GasderMIN system in Lysobacter enzymogenes (GCF_005954665.1, NZ_CP040656) is composed of 4 proteins bGSDM (WP_057949280.1) Trypsin_new (WP_158229849.1) CARD_Protease (WP_175429318.1) NLR_new (WP_057949283.1)

The CARD_NLR_Phospho system in Achromobacter deleyi (GCF_013116765.2, NZ_CP074375) is composed of 4 proteins Trypsin_Phospho (WP_171663676.1) Trypsin_new (WP_171663675.1) CARD_Protease_supposed (WP_171663674.1) NLR_new (WP_171663673.1)

The CARD_NLR_Subtilase system in Mesorhizobium sp. L-8-3 (GCF_016756615.1, NZ_AP023262) is composed of 4 proteins Subtilase (WP_202329294.1) Trypsin_new (WP_202305630.1) CARD_Protease_supposed (WP_202305632.1) NLR_IMG (WP_202329295.1)

The CARD_NLR_like system in Sphingomonas sanguinis (GCF_019297835.1, NZ_CP079203) is composed of 4 proteins Subtilase (WP_219018701.1) CARD_Protease_new (WP_219018702.1) NLR_new (WP_219018703.1) Endonuclease (WP_219021412.1)

Distribution of the system among prokaryotes

Among the 22,803 complete genomes of RefSeq, the CARD_NLR is detected in 80 genomes (0.35 %).

The system was detected in 57 different species.

Proportion of genome encoding the CARD_NLR system for the 14 phyla with more than 50 genomes in the RefSeq database.


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