An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities
| Autor: | Evan F. Haney, Robert E. W. Hancock, Suzana M. Ribeiro, Octavio L. Franco, Taia Maria Berto Rezende, Timothy K. Lu, Susana Elisa Moreno, Osmar N. Silva, C. de la Fuente-Núñez, William F. Porto, Isabel C. M. Fensterseifer, Paul D. Brown, Celio Faria-Junior |
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| Přispěvatelé: | MIT Synthetic Biology Center, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Research Laboratory of Electronics, de la Fuente Nunez, Cesar, Lu, Timothy K., Brown, Paul |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Peptide Microbial Sensitivity Tests Biology Article Microbiology Immunomodulation Mice 03 medical and health sciences Immune system In vivo Animals Humans Immunologic Factors chemistry.chemical_classification Multidisciplinary Innate immune system Drug discovery Bacterial Infections Blood Proteins Antimicrobial biology.organism_classification Immunity Innate In vitro Anti-Bacterial Agents 3. Good health Mice Inbred C57BL Disease Models Animal HEK293 Cells RAW 264.7 Cells 030104 developmental biology chemistry Immunology Female Peptides Bacteria |
| Zdroj: | Nature Scientific Reports |
| ISSN: | 2045-2322 1216-6901 |
| DOI: | 10.1038/srep35465 |
| Popis: | Antibiotic-resistant infections are predicted to kill 10 million people per year by 2050, costing the global economy $100 trillion. Therefore, there is an urgent need to develop alternative technologies. We have engineered a synthetic peptide called clavanin-MO, derived from a marine tunicate antimicrobial peptide, which exhibits potent antimicrobial and immunomodulatory properties both in vitro and in vivo. The peptide effectively killed a panel of representative bacterial strains, including multidrug-resistant hospital isolates. Antimicrobial activity of the peptide was demonstrated in animal models, reducing bacterial counts by six orders of magnitude, and contributing to infection clearance. In addition, clavanin-MO was capable of modulating innate immunity by stimulating leukocyte recruitment to the site of infection, and production of immune mediators GM-CSF, IFN-γ and MCP-1, while suppressing an excessive and potentially harmful inflammatory response by increasing synthesis of anti-inflammatory cytokines such as IL-10 and repressing the levels of pro-inflammatory cytokines IL-12 and TNF-α. Finally, treatment with the peptide protected mice against otherwise lethal infections caused by both Gram-negative and -positive drug-resistant strains. The peptide presented here directly kills bacteria and further helps resolve infections through its immune modulatory properties. Peptide anti-infective therapeutics with combined antimicrobial and immunomodulatory properties represent a new approach to treat antibiotic-resistant infections. Fundación Ramón Areces (Postdoctoral scholarship) Canada Research Chairs Brazil. National Council for Scientific and Technological Development (Postdoctoral scholarship) Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT-Brazil [300583/2016-8]) National Institutes of Health (U.S.) (grant 1R01EB017755) National Institutes of Health (U.S.) (1R21AI12166901) United States. Defense Threat Reduction Agency (HDTRA1-14-1-0007) United States. Defense Threat Reduction Agency (HDTRA1- 15-1-0050) United States. Army Research Office. Institute for Soldier Nanotechnologies (contract number W911NF-13-D-0001) |
| Databáze: | OpenAIRE |
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