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Keywords:

  • amphibian skin;
  • brevinin-1;
  • Candida albicans;
  • Rana;
  • ranatuerin-2;
  • temporin

Abstract: The emergence of strains of the human pathogen Candida albicans with resistance to commonly used antibiotics has necessitated a search for new types of antifungal agents. Six peptides with antimicrobial activity were isolated from norepinephrine-stimulated skin secretions from the foothill yellow-legged frog Rana boylii. Brevinin-1BYa (FLPILASLAA10KFGPKLF CLV20TKKC) was particularly potent against C. albicans [minimal inhibitory concentration (MIC) = 3 μm] and also active against Escherichia coli (MIC = 17 μm) and Staphylococcus aureus (MIC = 2 μm), but its therapeutic potential for systemic use is limited by its strong hemolytic activity (HC50 = 4 μm). The single amino acid substitution (Phe12 [RIGHTWARDS ARROW] Leu) in brevinin-1BYb resulted in a fourfold lower potency against C. albicans and the additional amino acid substitutions (Lys11 [RIGHTWARDS ARROW] Thr, Phe17 [RIGHTWARDS ARROW] Leu and Val20 [RIGHTWARDS ARROW] Ile) in brevinin-1BYc resulted in a ninefold decrease in activity. Two members of the ranatuerin-2 family and one member of the temporin family were also isolated from the secretions but showed relatively low potency against the three microorganisms tested.