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An amphibian-derived, cationic, α-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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    • "Most antimicrobial peptides bind nucleic acids (DNA and RNA) in vitro (Castle et al., 1999; Subbalakshmi and Sitaram, 1998; Boman et al., 1993), indicating that disruption of cell membranes might be combined with inhibition of DNA synthesis, transcription and/or RNA translation. Interestingly, S. cerevisiae proteins involved in DNA repair were purified as partners of dermaseptin S3, contributing to the understanding of its induction of apoptosis in yeast (Morton et al., 2007). The pea defensin PSD1 was shown to locate inside the nucleus of the model fungus Neurospora crassa, wherein it might alter cell cycle progression (Lobo et al., 2007). "
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    • "A recent study has shown that dermaseptins might have evolved a mechanism to induce the death of the cell during the invasion of fungal pathogens. It was found that when yeast was exposed to dermaseptin S 3 (1–16), a truncated derivative of dermaseptin S 3 with full activity, there were diagnostic markers of apoptosis, namely the appearance of reactive oxygen species and the fragmentation of nuclear DNA [Morton et al., 2007a,b]. However, many of dermaseptins are inactive on normal eukaryotic cells. "
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    • "In some of these reports, mutations of pro-apoptotic genes enhance resistance to AMP, indicating that induced microbial death is part of the peptide killing mechanism [9] [10] [11]. Intracellular rise of reactive oxygen species (ROS) is a marker of cell death and apoptosis in fungal cells. "
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