In Vivo Efficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization
| Autor: | Uru Malik, Lai Yue Chan, Isabel C. M. Fensterseifer, Osmar N. Silva, David J. Craik, Octavio L. Franco, Richard J. Clark, Norelle L. Daly |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Cell Survival Antimicrobial peptides Peptide Microbial Sensitivity Tests In Vitro Techniques Biology Staphylococcal infections medicine.disease_cause Peptides Cyclic Microbiology Mice In vivo medicine Animals Humans Pharmacology (medical) Pharmacology chemistry.chemical_classification Skin Diseases Bacterial Staphylococcal Infections Chemistry Biosynthesis medicine.disease Antimicrobial Trypsin Cyclic peptide Anti-Bacterial Agents Mice Inbred C57BL Infectious Diseases chemistry Biochemistry Cyclization Staphylococcus aureus Female Anura Peptides Trypsin Inhibitors medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 59:2113-2121 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.04324-14 |
| Popis: | 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 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 cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weak in vitro inhibitory activities against S. aureus , but several had strong antibacterial activities against S. aureus in an in vivo murine wound infection model. pYR, an immunomodulatory peptide from Rana sevosa , was the most potent, with 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. |
| Databáze: | OpenAIRE |
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