An amphibian-derived, cationic, α-helical antimicrobial peptide kills yeast by caspase-independent but AIF-dependent programmed cell death

The dermaseptins are a family of antimicrobial peptides from the tree-frog Phyllomedusa sauvagii. Yeast exposed to dermaseptin S3(1-16), a truncated derivative of dermaseptin S3 with full activity, showed diagnostic markers of yeast apoptosis: the appearance of reactive oxygen species and fragmentation of nuclear DNA. This process was independent of the yeast caspase, Yca1p. Screening of a non-essential gene deletion collection in yeast identified genes that conferred resistance to dermaseptin S3(1-16): izh2 Delta, izh3 Delta, stm1 Delta and aif1 Delta, all known to be involved in regulating yeast apoptosis. The appearance of apoptotic markers was reduced in these strains when exposed to the peptide. Dermaseptin S3(1-16) was shown to interact with DNA, and cause DNA damage in vivo, a process known to trigger apoptosis. Supporting this, a dermaseptin S3(1-16) affinity column specifically purified Stm1p, Mre1p and Htb2p; DNAbinding proteins implicated in yeast apoptosis and DNA repair. Thus, amphibians may have evolved a mechanism to induce cell suicide in invading fungal pathogens.