Brevinin-1BYa: a naturally occurring peptide from frog skin with broad-spectrum antibacterial and antifungal properties

摘要

Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC) is a cationic alpha-helical peptide containing an intramolecular disulphide bridge that is present in skin secretions of the foothill yellow-legged frog Rana boylii. A synthetic replicate of the peptide showed growth inhibitory activity against a range of reference strains of Gram-positive and Gram-negative bacteria, against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (minimum inhibitory concentration (MIC) = 2.5 mu M), and against reference strains and clinical isolates of the opportunistic yeast pathogens Candida albicans, Candida tropicalis. Candida krusei and Condida parapsilosis (MIC <= 10 mu M). However. the therapeutic potential of the peptide, especially for systemic applications. is restricted by its high haemolytic activity against human erythrocytes (LD50 = 10 mu M). Replacement of the cysteine residues in brevinin-1BYa by serine produced an acyclic analogue with eight-fold reduced haemolytic activity that retained high potency against Gram-positive bacteria, including strains of MRSA (MIC = 5 mu M). however activities against Gram-negative bacteria and yeast species were reduced. It is suggested that brevinin-1BYa represents a candidate for a drug development, particularly for topical applications against antibiotic-resistant microorganisms. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.