FIGURE 2.

Microbial stimuli activate stress kinases in the integrated stress response (ISR) and the unfolded protein response (UPR) pathways. Microorganisms are able to induce the ISR and UPR through a variety of mechanisms. Type III and IV bacterial secretion systems (T3SS and T4SS) promote ER restructuring and the release of microbial effector proteins that can activate PERK and the UPR. PKR can be activated through PKR activating stimuli other than dsRNA. Calcium can be released through quorum sensing molecules and ROS generation, which also induces oxidative stress and protein misfolding, in turn activating the UPR and PERK. Nutrient and iron deprivation may be induced by microbes and their products promoting activation of GCN2 and HRI, respectively.