The fungal UPR: A regulatory hub for virulence traits in the mold pathogen Aspergillus fumigatus

Aspergillus fumigatus is an opportunistic pathogen that is responsible for a life-threatening fungal infection known as invasive aspergillosis. Current therapies for the treatment of this disease continue to be associated with a poor outcome, so there is a need for more information about aspects of the fungus–host interaction that could offer novel targets for drug intervention. One attractive possibility is the unfolded protein response (UPR), an intracellular signaling network that helps the fungus meet the demand for secretion in the host environment. The major function of the UPR is to mitigate ER stress by maintaining an equilibrium between the load of client proteins entering the endoplasmic reticulum (ER) and the protein folding capacity of the organelle. However, recent findings suggest that A. fumigatus, as well as several other pathogenic fungi, also rely upon this pathway for virulence. In this review, we provide an update on the A. fumigatus UPR, discuss emerging evidence that the UPR is situated at the nexus of a number of physiological functions that are vital for the virulence of this fungus, and suggest exciting possibilities for future therapeutic targeting of this pathway for the treatment of aspergillosis.