Inhibition of Staphylococcus aureus pathogenesis in vitro and in vivo by RAP-binding peptides
| Autor: | Ningsheng Shao, Guang Yang, Dongping Wang, Yanning Xue, Huichai Cheng, Nongle Liu, Bo Gao, Chuan Liu, Yaping Gao, Shanru Li, Beifen Shen |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Staphylococcus aureus
Phage display Physiology RNAIII Recombinant Fusion Proteins Peptide Biology Staphylococcal infections medicine.disease_cause Biochemistry Microbiology Mice Cellular and Molecular Neuroscience Endocrinology Bacterial Proteins Peptide Library In vivo medicine Animals RNA Antisense Peptide library chemistry.chemical_classification Cellulitis Staphylococcal Infections medicine.disease Molecular biology RNA Bacterial chemistry Target protein Carrier Proteins Protein Binding |
| Zdroj: | Peptides. 24:1823-1828 |
| ISSN: | 0196-9781 |
| DOI: | 10.1016/j.peptides.2003.09.017 |
| Popis: | Staphylococcus aureus cause many diseases by producing toxins, whose synthesis is regulated by quorum-sensing mechanisms. S. aureus secretes a protein termed RNAIII activating protein (RAP) which autoinduces toxin production via the phosphorylation of is target protein TRAP. Mice vaccinated with RAP were protected from S. aureus infection, suggesting that RAP is an useful target for selecting potential therapeutic molecules to inhibit S. aureus pathogenesis. We show here that RAP (native and recombinant) was used to select RAP-binding peptides (RBPs) from a random 12-mer phage-displayed peptide library. Two RBPs were shown to inhibit RNAIII production in vitro (used a marker for pathogenesis). The peptide WPFAHWPWQYPR, which had the strongest inhibitory activity, was chemically synthesized and also expressed in Escherichia coli as a GST-fusion. Both synthetic peptide and GST-fusion peptide decreased RNAIII levels in a dose-dependent manner. The GST-fusion peptide was also shown to protect mice from a S. aureus infection in vivo (tested in a murine cutaneous S. aureus infection model). Our results suggest the potential use of RAP-binding proteins in treating clinical S. aureus infections. |
| Databáze: | OpenAIRE |
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