U Malik,O. N. Silva, I. C. M. Fensterseifer, L. Y. Chan, R. J. Clark, O. L. Franco, N. L. Daly, D. J. Craik, Antimicrob. Agents Chemother. Published on-line 26 January, 2015 DOI: 10.1128/AAC.04324-14
Staphylococcus aureus is a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem and the development of novel antimicrobial agents is crucial. Antimicrobial peptides (AMPs) from natural resources offer potential as new treatments against Staphylococcal infections. In the current study we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclised synthetic analogues of these peptides. Structures of the peptides were elucidated by NMR spectroscopy revealing high structural and sequence similarity with each other and with SFTI-1. SFTI-1 is an ultra-stable cyclic peptide isolated from sunflower seeds with sub-nanomolar trypsin inhibitory activity and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were non-hemolytic, non-cytotoxic and had potent trypsin inhibitory activity similar to SFTI-1. They demonstrated weak in vitro inhibitory activity against S. aureus, but several had potent antibacterial activity against S. aureus in an in vivo murine wound infection model. pYR, an immuno-modulatory peptide from Rana sevosa was the most potent with a complete bacterial clearance at 3 mg.kg-1. Cyclization of the peptides improved their stability, but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.