Dias, Susana A.Miguel Freire, JoãoPérez-Peinado, Clara, 1991-Domingues, Marco M.Gaspar, DianaVale, NunoGomes, PaulaAndreu Martínez, DavidHenriques, Sónia T.Castanho, Miguel A.R.B.Veiga, Ana Salomé2017-07-062017-07-062017Dias SA, Freire JM, Pérez-Peinado C, Domingues MM, Gaspar D et al. New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins. Frontier in Microbiology. 2017;8:775. DOI: 10.3389/fmicb.2017.007751664-302Xhttp://hdl.handle.net/10230/32515The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Pseudomonas aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of P. aeruginosa cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties.application/pdfeng© 2017 Dias, Freire, Pérez-Peinado, Domingues, Gaspar, Vale, Gomes, Andreu, Henriques, Castanho and Veiga. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fmicb.2017.00775Antimicrobial peptides (AMPs)Antimicrobial peptides (AMPs)Cell-penetrating peptides (CPPs)Minimum inhibitory concentration (MIC)Minimal bactericidal concentration (MBC)Membrane permeabilizationAtomic force microscopy (AFM)info:eu-repo/semantics/openAccess