The antimicrobial activity of chemerin-derived peptide p4 requires oxidative conditions
| Autor: | Arkadiusz Borek, Urszula Godlewska, Oliwia Bochenska, Aneta Zegar, Patryk Kuleta, Piotr Brzoza, Agnieszka Morytko, Bernadetta Bilska, Artur Osyczka, Joanna Cichy, Elżbieta Pyza, Andrzej Kozik, Krzysztof Murzyn, Brian A. Zabel |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytochrome antimicrobial peptide (AMP) Human skin MRSA Skin infection host-pathogen interaction medicine.disease_cause Biochemistry Mice chemotaxis bacteria Skin biology integumentary system Chemistry Staphylococcal Infections Antimicrobial Anti-Bacterial Agents Staphylococcus aureus (S. aureus) host defense Staphylococcus aureus Intercellular Signaling Peptides and Proteins Female Chemokines Oligopeptides Oxidation-Reduction chemerin Methicillin-Resistant Staphylococcus aureus skin Immunology Microbial Sensitivity Tests Microbiology 03 medical and health sciences epidermis medicine Chemerin Animals Humans Molecular Biology 030102 biochemistry & molecular biology adipokine Chemotaxis Cell Biology Skin Diseases Bacterial medicine.disease Mice Inbred C57BL Oxidative Stress 030104 developmental biology Coenzyme Q – cytochrome c reductase biology.protein |
| Popis: | Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein abundantly produced in the skin epidermis. Despite the fact that most of the bactericidal activity present in human skin exudates is chemerin-dependent, just how chemerin shapes skin defenses remains obscure. Here we demonstrate that p4, a potent antimicrobial human chemerin peptide derivative, displays killing activity against pathogenic methicillin-resistant Staphylococcus aureus strains and suppresses microbial growth in a topical skin infection model. Mechanistically, we show that p4 homodimerization is required for maximal bactericidal activity and that an oxidative environment, such as at the skin surface, facilitates p4 disulfide bridge formation, required for the dimerization. p4 led to rapid damage of the bacterial internal membrane and inhibited the interaction between the membranous cytochrome bc(1) complex and its redox partner, cytochrome c. These results suggest that a chemerin p4–based defense strategy combats bacterial challenges at the skin surface. |
| Databáze: | OpenAIRE |
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