The vertebrate peptide antibiotics dermaseptins have overlapping structural features but target specific microorganisms

The physiological significance of the occurrence of sequence similar antimicrobial Peptides in frog skin, as the bombinins in Bombina, the magainins in Xenopus, and the dermaseptins in Phyllomedusa, is a major unanswered question. Dermaseptins s1, s2, s3, s4, and s5, a family of cationic (lysine-rich), amphipathic Antifungal peptides of 28-34 residues were thus synthesized, purified to homogeneity, and evaluated for their growth-inhibition activity in vitro against various pathogenic Microorganisms. Although all five of these Peptides shared a similar spectrum of lytic activity against the filamentous fungi that are responsible for opportunistic lethal infections that follow the immunodeficiency syndrome or the use of immunosuppressive agents, they exhibited marked differences in their potencies to arrest the growth of Gram-positive and Gram-negative pathogenic bacteria and yeasts. Likewise, whereas dermaseptins s1 and s5 were devoid of hemolytic activity, dermaseptin s4 caused lysis of erythrocytes at micromolar concentrations. The dermaseptins exhibited dramatic synergy of action upon combination, resulting in some cases in a 100-fold increase in Antibiotic activity of the mixture over the activity of the Peptides separately. Shortening the peptide chain of dermaseptin s3 to dermaseptin s3-(1-16)-NH2 did not affect the antimicrobial potency of the peptide. Further reduction of the chain length yielded peptide derivatives gradually showing reduced activity. Surprisingly, however, analogs of dermaseptin s3 as shorter as 10-12 residues in length remained fully active against Enterococcus faecalis, Cryptococcus neoformans, and against Aeromonas caviae, the causal agent of red-leg disease in amphibians. Overall, these results suggest that, despite 40% sequence similarities, the dermaseptins have distinct spectra of anti-microbial activity and may act in concert to circumvent host invasion by providing frogs with a better shielding against a broad array of Microorganisms. They also demonstrate the potential usefulness of short analogs of these Peptides as potential candidates for biorational design of germicides.