Lost after translation: post-translational modifications by bacterial type III effectors

Abstract

Many Gram-negative bacterial pathogens use the type III secretion system to deliver effector proteins into host cells. These effectors use various mechanisms to exploit host processes to the advantage of the pathogen. A large group of effectors use post-translational modifications, either reversible or irreversible, to manipulate host proteins, and while most of these mechanisms mimic eukaryotic activities, others appear to be unique biochemical functions. Deciphering such mechanisms and identifying the host targets of these effectors sheds light on eukaryotic signaling pathways and immune responses.

Figure 1

Post-translational modifications using small molecule substrates. (a) YpkA phosphorylates an active GTP-bound form of Gαq to prevent G-protein activation. (b) MAPKK and IKK are activated upon phosphorylation of serine and threonine residues in the activation loop by MAPKKKs. YopJ acetylates these residues, thereby preventing their phosphorylation and activation. (c) ExoT ADP-ribosylates CrkI and CrkII. This modification disrupts the assembly of the focal adhesion complex and phagocytosis. (d) VopS uses ATP to AMPylate Rho-family GTPases and inhibit their activity, resulting in collapse of the actin cytoskeleton.

Figure 2

Small protein post-translational modifications. AvrPtoB poly-ubiquitinates pattern recognition receptors (PRRs) resulting in their degradation by the proteasome. Eliminating PRRs hampers the cell’s ability to recognize invading bacteria and activate immune responses.

Figure 3

Irreversible post-translational modifications. (a) AvrPphB cleaves the plant kinase PBS1. RPS5 functions as a “guard” that recognizes the cleaved PBS1 and elicits an immune response. (b) OspF carries out a β-elimination reaction that irreversibly removes the phosphate from phosphorylated MAPKs, resulting in an inactive kinase that can no longer be activated. (c) VopC de-amidates a glutamine residue on Rho-GTPases to activate them and mediate bacterial invasion.