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Sci Rep. 2016 Nov 2;6:35465. doi: 10.1038/srep35465.

An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities.

Author information

1
Departamento de Biologia, Instituto de Ciências Biológicas, Programa de pós-graduação em Genética e Biotecnologia, Universidade Federal de Juiz de Fora, Juiz de Fora-MG, Brazil.
2
S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.
3
Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
4
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
5
Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
6
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
7
Harvard Biophysics Program, Harvard University, Boston, Massachusetts, United States of America.
8
The Center for Microbiome Informatics and Therapeutics, Cambridge, Massachusetts, United States of America.
9
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
10
Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil.
11
Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, Brazil.
12
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
13
Curso de Odontologia, Universidade Católica de Brasília, Brazil.
14
Pós-graduação em Ciências da Saúde, Universidade de Brasília, Brazil.

Abstract

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.

PMID:
27804992
PMCID:
PMC5090204
DOI:
10.1038/srep35465
[Indexed for MEDLINE]
Free PMC Article

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