title: An amphibian-derived, cationic, alpha-helical antimicrobial peptide kills yeast by caspase-independent but AIF-dependent programmed cell death.
abstract: 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): izh2Delta, izh3Delta, stm1Delta and aif1Delta, 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, Mre11p and Htb2p; DNA-binding proteins implicated in yeast apoptosis and DNA repair. Thus, amphibians may have evolved a mechanism to induce cell suicide in invading fungal pathogens.
authors.affiliation: Centre for Biomolecular Sciences, School of Biology, University of St. Andrews, The North Haugh, St. Andrews, KY16 9ST, UK.
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Morton
authors.forename: Sandra Costa
authors.initials: SC
authors.lastname: Dos Santos
authors.forename: Peter
authors.initials: P
authors.lastname: Coote
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D004249:DNA Damage; D004271:DNA, Fungal / Q000737:chemistry / Q000187:drug effects; D025141:Drug Resistance, Fungal / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000378:metabolism; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D029845:Amphibian Proteins; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D051033:Apoptosis Inducing Factor; D004271:DNA, Fungal; D006657:Histones; D010718:Phosphatidylserines; D029701:Saccharomyces cerevisiae Proteins; C070905:dermaseptin; D020169:Caspases; C456272:MCA1 protein, S cerevisiae