Isolation of peptides of the brevinin-1 family with potent candidacidal activity from the skin secretions of the frog Rana boylii.
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.
Conlon
J M
JM
Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, 17666 Al-Ain, UAE. jmconlon@uaeu.ac.ae
Sonnevend
A
A
Patel
M
M
Davidson
C
C
Nielsen
P F
PF
Pál
T
T
Rollins-Smith
L A
LA
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
D029845:Amphibian Proteins; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; C078413:brevinin-1 protein, Rana