Isolation of peptides of the brevinin-1 family with potent candidacidal activity from the skin secretions of the frog Rana boylii

• Published in: The journal of peptide research Vol. 62; no. 5; pp. 207 - 213
• Main Authors: Conlon, J. M., Sonnevend, Á., Patel, M., Davidson, C., Nielsen, P.F., Pál, T., Rollins-Smith, L.A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2003; Wiley
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Amphibian Proteins; amphibian skin; Animals; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - isolation & purification; Antimicrobial Cationic Peptides - pharmacology; Biochemical Research Methods; Biochemistry & Molecular Biology; brevinin-1; Candida albicans; Candida albicans - drug effects; Candida albicans - growth & development; Chromatography, High Pressure Liquid; Erythrocytes - drug effects; Escherichia coli - drug effects; Escherichia coli - growth & development; Humans; Life Sciences & Biomedicine; Mass Spectrometry; Microbial Sensitivity Tests; Molecular Sequence Data; Rana; ranatuerin-2; Ranidae - genetics; Ranidae - metabolism; Science & Technology; Skin - metabolism; Skin - secretion; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development; temporin; Time Factors; Candida albicans; temporin; NORTH-AMERICAN FROGS; HELICAL ANTIMICROBIAL PEPTIDES; Rana; ranatuerin-2; ANTIBACTERIAL; MECHANISMS; STRUCTURAL FEATURES; amphibian skin; brevinin-1; RESISTANCE; AMPHIBIAN DECLINES; ALBICANS; GENUS RANA; HYDROPHOBIC MOMENT
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1034/j.1399-3011.2003.00090.x

: 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 → Leu) in brevinin‐1BYb resulted in a fourfold lower potency against C. albicans and the additional amino acid substitutions (Lys11 → Thr, Phe17 → Leu and Val20 → 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.