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

Centre for Biomolecular Sciences, School of Biology, University of St. Andrews, The North Haugh, St. Andrews, KY16 9ST, UK.
Molecular Microbiology (Impact Factor: 5.03). 08/2007; 65(2):494-507. DOI: 10.1111/j.1365-2958.2007.05801.x
Source: PubMed

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.

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