Peptidomic Analysis of Skin Secretions of the Caribbean Frogs and (Leptodactylidae) Identifies an Ocellatin with Broad Spectrum Antimicrobial Activity.

Ocellatins are peptides produced in the skins of frogs belonging to the genus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Barbour 1906 and Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from (ocellatin-1I together with its (1-16) fragment, ocellatin-2I and its (1-16) fragment, and ocellatin-3I) and four ocellatins from (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH) was active against an antibiotic-resistant strain of and reference strains of , , , and (minimum inhibitory concentrations (MICs) in the range 31.25-62.5 μM), and was the only peptide active against Gram-positive (MIC = 31.25 μM) and (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens.