Silva, O. N.de la Fuente-Núñez, C.Haney, E. F.Fensterseifer, I. C. M.Ribeiro, S. M.Porto, W. F.Brown, P.Faria-Junior, C.Rezende, T. M. B.Moreno, S. E.Lu, T. K.Hancock, R. E. W.Franco, O. L.2016-12-022016Silva, O. N., C. de la Fuente-Núñez, E. F. Haney, I. C. M. Fensterseifer, S. M. Ribeiro, W. F. Porto, P. Brown, et al. 2016. “An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities.” Scientific Reports 6 (1): 35465. doi:10.1038/srep35465. http://dx.doi.org/10.1038/srep35465.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626195Antibiotic-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.en-USJournal Article2016-12-0210.1038/srep35465