Insight into Invertebrate Defensin Mechanism of Action
| Autor: | Tanja Schneider, Evelyne Bachère, Hans-Georg Sahl, André Aumelas, Paulina Schmitt, Delphine Destoumieux-Garzón, Miriam Wilmes, Martine Pugnière |
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| Rok vydání: | 2010 |
| Předmět: |
Oyster
Antimicrobial peptides Biology Biochemistry 03 medical and health sciences chemistry.chemical_compound biology.animal medicine 14. Life underwater Molecular Biology Defensin 030304 developmental biology 0303 health sciences integumentary system Lipid II fungi 030302 biochemistry & molecular biology hemic and immune systems Cell Biology respiratory system Plectasin bacterial infections and mycoses Beta defensin chemistry Mechanism of action Peptidoglycan medicine.symptom medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 285:29208-29216 |
| ISSN: | 0021-9258 |
| Popis: | Three oyster defensin variants (Cg-Defh1, Cg-Defh2, and Cg-Defm) were produced as recombinant peptides and characterized in terms of activities and mechanism of action. In agreement with their spectrum of activity almost specifically directed against Gram-positive bacteria, oyster defensins were shown here to be specific inhibitors of a bacterial biosynthesis pathway rather than mere membrane-active agents. Indeed, at lethal concentrations, the three defensins did not compromise Staphylococcus aureus membrane integrity but inhibited the cell wall biosynthesis as indicated by the accumulation of the UDP-N-acetylmuramyl-pentapeptide cell wall precursor. In addition, a combination of antagonization assays, thin layer chromatography, and surface plasmon resonance measurements showed that oyster defensins bind almost irreversibly to the lipid II peptidoglycan precursor, thereby inhibiting the cell wall biosynthesis. To our knowledge, this is the first detailed analysis of the mechanism of action of antibacterial defensins produced by invertebrates. Interestingly, the three defensins, which were chosen as representative of the oyster defensin molecular diversity, bound differentially to lipid II. This correlated with their differential antibacterial activities. From our experimental data and the analysis of oyster defensin sequence diversity, we propose that oyster defensin activity results from selective forces that have conserved residues involved in lipid II binding and diversified residues at the surface of oyster defensins that could improve electrostatic interactions with the bacterial membranes. |
| Databáze: | OpenAIRE |
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