a Functional Genomics Study

The inhibitory action of the amphibian-derived cationic peptides DsS3(1-16) and Mag2 has been proposed to be due to membrane disruption. In fact, we have shown that the mode of action of the two peptides is more complex than membrane disruption and subtly different. For the first time we have shown that both peptides are able to pass into the interior of the cell and disrupt vital intracellular functions. In the case of DsS3(1-16), the peptide triggers apoptosis via damage to cellular DNA. This is the first time it has been shown that the inhibitory action of an α-helical, cationic peptide is due to the specific induction of microbial apoptosis. In contrast, Mag2 did not induce apoptosis but was shown to specifically interfere with DNA replication. Thus, despite similar structure, the peptides have different modes of action that could explain why they display synergy in combination. One intriguing conclusion from this work is the observation that amphibians may have evolved a mechanism to induce cell suicide in invading fungal pathogens.