Table 1. Effectors and toxins that interact with the pyrin inflammasome.

This table lists all known or toxins and effectors that have been shown to or are predicted to either trigger pyrin activation or inhibit pyrin inflammasome formation. Effectors and toxins that target RhoA may do so by several different mechanisms. First, many effectors and toxins inactivate RhoA through covalent modification that prevents loading of GTP or binding to transducers. The amino acid residues modified in RhoA, Rac1 and Cdc42 are noted for those targets that are known. Effectors can also function as GAPs that shift the majority of RhoA in the host cell from the GTP to the GDP-bound state effectively preventing interactions with transducers. Finally, Yersinia YopT cleaves RhoA from the membrane resulting in mislocalization and loss of interaction with transducers. There are also two Yersinia effectors that inhibit the pyrin inflammasome. YopM binds to pyrin and hijacks PRKs to keep pyrin phosphorylated and 14–3-3 bound. YopJ limits inflammasome function by acetylating MAPKKs, which may directly reduce activation of pyrin or decrease expression of inflammasome components such as IL-1β. Purified commercially-available Cnf toxin has been shown to inhibit the pyrin inflammasome by deamidation of RhoA, leading to its constitutive activation. The context in which the interaction of each effector or toxin with the pyrin inflammasome has been studied is described.

Pathogen and toxin/effector	Mechanism	Targets	Inflammasome outcome	Context	Reference
Burkholderia cenocepacia TecA	Deamidation	RhoA (N41), Rac1 (N39), Cdc42 (?)	Activator	Ex vivo, in vivo infections	[17], [24]
Clostridium difficile TcdA/B	Glucosylation	RhoA (T37), Rac1, Cdc42 (T32)	Activator	Ex vivo intoxications and infections	[17]
Clostridium botulinum C3	ADP Ribosylation	RhoA (N41)	Activator	Ex vivo intoxications	[17]
Staphylococcus aureus EDIN-B	ADP Ribosylation	RhoA (N41)	Activator	Predicted	NA
Bordetella pertussis Ptx	ADP Ribosylation	Gαi, Gα0 (C351)	Activator	In vivo intoxication	[23]
Vibrio parahaemolyticus VopS	Adenylylation	RhoA (T37), Rac1 & Cdc42 (T35)	Activator	Ex vivo ectopic intoxication (LFn)	[17]
Histophilus somni IbpA Fic1/2	Adenylylation	RhoA (Y34), Rac1 & Cdc42 (Y32)	Activator	Ex vivo ectopic intoxication (LFn)	[17]
Pseudomonas aeruginosa ExoS GAP	GAP	RhoA, Rac1 & Cdc42	Activator	Predicted	NA
Pseudomonas aeruginosa ExoT GAP	GAP	RhoA, Rac1 & Cdc42	Activator	Predicted	NA
Yersinia spp. YopE	GAP	RhoA, Rac1 & Cdc42	Activator	Ex vivo, in vivo infections	[21], [25], [26]
Yersinia spp. YopT	Cysteine protease	RhoA, Rac1 & Cdc42	Activator	Ex vivo, in vivo infections	[21], [26]
Yersinia spp. YopM	Hijack PRKs to phosphorylate pyrin	Pyrin, PRKs, RSKs	Inhibitor	Ex vivo, in vivo infections	[21], [25]
Yersinia spp. YopJ	Acetylation	MAPKKs and TAK1	Inhibitor	Ex vivo, in vivo infections	[55], [54]
Cnf (commercial)	Deamidation	RhoA (Q63)	Inhibitor	Ex vivo intoxication	[18]