Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics

Table 1

Main classes of host defense peptides (HDPs) shown to induce RCD.

Main classes of RCD-inducing antifungal peptides
Name	Source	Mode of action apart from RCD induction and mitochondrial dysfunction
A. Helical and extended peptides
Periplanetasin-2	Cockroach (Periplaneta americana)	Lipid peroxidation, caspase activation
Scolopendin	Centipedes; Class Chilopoda	Metacaspase activation
Lactoferrin	Bovine/human	Metacaspase activation, inhibition of membrane H^+-ATPase Pma1
B. γ–core containing peptides
Plant defensin RsAFP2	Radish (Raphanus sativus)	Interaction with fungal-specific glucosylceramide, induction of cell wall stress, ceramide accumulation, septin mislocalization, metacaspase independent
Plant defensin HsAFP1	Coral bell (Heuchera sanguinea)	Interaction with PA and PI phospholipids, accumulation at buds and septa, internalization, pH dependent activity in vitro
Plant defensin-like peptide ApDef-1	Adenanthera pavonina	Cell cycle dysfunction, metacaspase activation
Insect defensin Coprisin	Dung beetle Family Scarabaeoidea	Dysfunctional mitochondrial Δψ and cytochrome C release
Fungal defensin-like peptide NFAP	Neosartorya fischeri	Cell wall dysfunction, accumulation of nuclei at broken hyphal tips
Fungal defensin-like peptide AFP	Aspergillus giganteus	Cell wall perturbation
Neutrophil defensin hNP-1	Human	Membrane permeabilization and depolarization
Beta defensin hβD-2	Human	RCD modulated by Bcr1 and Ssd1 proteins in C. albicans
Kinocidins (e.g., CXCL4, CXCL8)	Mammalian	Perturb membrane energetics and inhibit macromolecular synthesis; pH-related activity in vitro; RCD modulated by Bcr1 and Ssd1 proteins in C. albicans

Note that Histatin-5 and plant defensin-like peptide LpDef1 were not integrated in the table as their potential induction of RCD is still under investigation.