Targeting intrinsic cell death pathways to control fungal pathogens

Abstract Fungal pathogens pose an increasing threat to public health. Limited clinical drug regimens and emerging drug-resistant isolates challenge infection control. The global burden of human fungal pathogens is estimated at 1 billion infections and 1.5 million deaths annually. In addition, plant fungal pathogens increasingly threaten global food resources. Novel strategies are needed to combat emerging fungal diseases and pan-resistant fungi. An untapped mechanistically novel approach is to pharmacologically activate the intrinsic cell death pathways encoded by pathogenic fungi. This strategy is analogous to new anti-cancer therapeutics now entering the clinic. Here we summarize the best understood examples of cell death mechanisms encoded by pathogenic fungi, contrast these to mammalian cell death pathways, and highlight the gaps in knowledge towards identifying potential death effectors as druggable targets.