title: Isolation of peptides of the brevinin-1 family with potent candidacidal activity from the skin secretions of the frog Rana boylii.
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 microm] and also active against Escherichia coli (MIC = 17 microm) and Staphylococcus aureus (MIC = 2 microm), but its therapeutic potential for systemic use is limited by its strong hemolytic activity (HC50 = 4 microm). 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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, 17666 Al-Ain, UAE. jmconlon@uaeu.ac.ae
authors.forename: J M
authors.initials: JM
authors.lastname: Conlon
authors.forename: A
authors.initials: A
authors.lastname: Sonnevend
authors.forename: M
authors.initials: M
authors.lastname: Patel
authors.forename: C
authors.initials: C
authors.lastname: Davidson
authors.forename: P F
authors.initials: PF
authors.lastname: Nielsen
authors.forename: T
authors.initials: T
authors.lastname: Pál
authors.forename: L A
authors.initials: LA
authors.lastname: Rollins-Smith
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D029845:Amphibian Proteins; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011898:Ranidae / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013997:Time Factors
chemical_list: D029845:Amphibian Proteins; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; C078413:brevinin-1 protein, Rana