Fig 1.
Pyroptosis across the tree of life.
The top model depicts pyroptotic bacterial and mammalian cells with shared and unique signaling pathways. In this case, bacterial pyroptosis is induced by phage infection and unknown PAMPs or other signals that trigger bGSDM activation. Mammalian pyroptosis is induced by intracellular bacteria (and viral infection; not shown), leading to mGSDM activation through PAMPs or other signals, and pore formation on the plasma membrane, bacterial membranes, and mitochondria. Examples of known and predicted pathogen-encoded inhibitors are indicated with flat arrowheads. The bottom checklist depicts relative sizes of gasdermin pores across the tree of life and select features. The bacterial species are abbreviated to Runella (Runella zeae IMG ID 2525253496) and Bacteroidetes (unclassified Bacteroidetes metagenomic isolate IMG ID 2806880301). bGSDM, bacterial gasdermin; CTD, C-terminal domain; mGSDM, mammalian gasdermin; PAMP, pathogen-associated molecular pattern.
Fig 2.
bGSDM operons suggest a diversity of unexplored signaling mechanisms.
From top to bottom, operons are from Ideonella sp. (IMG ID 2684147428), Runella zeae (IMG ID 2525253496), Oscillochloris trichodetes (IMG ID 650112614), and Sphingobium sp. (IMG ID 2855415098). The Sphingobium operon is of a similar architecture to the Lysobacter enzymogenes operon, which defends against phages when expressed in E. coli, but lacks the closely associated genes encoding lysozyme and phospholipase proteins. Genes are illustrated with potential roles in the upstream activation of bGSDM signaling or as downstream effectors. Select domains with potential roles in pathogen sensing are italicized above genes. Genes and domains are abbreviated as follows: peptidase (Peptidase U49), caspase (caspase-like including Peptidase C14 and CHAT), C-type lectins or CTL (typically annotated as formylglycine-generating enzymes or FGS), LRR (leucine-rich repeats), NLR (nucleotide-binding oligomerization domain (NOD)-like receptor), NACHT (NAIP, CIIA, HET-E, and TP1 domain), amidase (N-acetylmuramoyl-L-alanine amidase), tubulin (FtsZ), and trypsin (trypsin-like).