Fig 1.
Guard or decoy mechanisms of ETI in a host cell.
A generic pathogen uses a secretion system to translocate 4 effectors (E1-4) into a host cell. Effectors can be equivalent to Avr proteins and are detected by different guard or decoy proteins, which can be equivalent to R proteins. (A) The guard binds to and is inhibited by the guardee and is released to promote an immune response when E1 modifies the guardee (circle with lightning bolt). (B) Effector E2 binds to and modifies the guardee, leading to a conformational change and enhanced binding affinity for the guard protein which becomes activated. (C) The decoy mimics the effector target (guardee) and inhibits the guard. Modification of the decoy by E3 leads to its loss and activation of the guard. (D) The decoy is integrated into and inhibits the guard and modification of the decoy domain by E4 leads to its loss and activation of the guard. Figure adapted from images created with BioRender.com.
Table 1.
Summary of guard or integrated decoy mechanisms of bacterial effector triggered immunity.
Fig 2.
Guard or integrated decoy mechanisms of bacterial ETI in a host cell.
The guard or integrated decoy in each mechanism is lettered. RIPK1 (A): Upon TLR stimulation by LPS, complex I is assembled at the plasma membrane which contains RIPK1, and leads to activation of TAK1 and IKKβ, stimulation of the NF-κB pathway and gene expression. Effector YopJ translocated by a type III secretion system (T3SS) in extracellular Yersinia inhibits TAK1 and IKKβ resulting in the formation of complex II (RIPoptosome) containing FADD and activated caspase-8 (Casp8) which can process GSDMD and pro-IL-1β. N-GSDMD pore formation releases IL-1β and promotes pyroptosis. Pyrin (B): RhoA inactivation by effectors YopE or YopT translocated by Yersinia ΔyopM removes negative regulation of pyrin by PRK and allows dephosphorylation by a phospho-protein phosphatase (PPP). Dephosphorylated pyrin forms an inflammasome with caspase-1 (Casp1) leading to release of active Casp1, N-GSDMD pore formation, processing and release of IL-1β and pyroptosis. NLRP3 (C): Extracellular E. coli secretes CNF1 toxin which is internalized by receptor-mediated endocytosis. CNF1 locks Rac2 in a GTP bound state, which activates the Pak1/2 kinases that phosphorylate NLRP3 resulting in inflammasome activation and active Casp1. Casp1 processes pro-IL-1β and IL-1β is released by a process that does not involve N-GSDMD pore formation or pyroptosis (dashed arrow). NLRP1B (D): Extracellular B. anthracis secretes LF toxin which is internalized by receptor-mediated endocytosis. LF cleaves the N-terminus of NLRP1B, and the resulting peptide is degraded by the proteosome. The liberated C-terminal CARD fragment can form an inflammasome, leading to active Casp1, N-GSDMD pore formation, processing and release of IL-1β and pyroptosis. GSDMA (E): Intracellular S. pyogenes secretes SpeB toxin which cleaves pro-GSDMA, leading to N-GSDMA pores and pyroptosis. Figure adapted from images created with BioRender.com.