AUTHOR=Dias Susana A. , Freire João M. , Pérez-Peinado Clara , Domingues Marco M. , Gaspar Diana , Vale Nuno , Gomes Paula , Andreu David , Henriques Sónia T. , Castanho Miguel A. R. B. , Veiga Ana S. 

TITLE=New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00775

DOI=10.3389/fmicb.2017.00775

ISSN=1664-302X

ABSTRACT=<p>The 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 <italic>Staphylococcus aureus</italic>, MRSA, <italic>Escherichia coli</italic>, and <italic>Pseudomonas aeruginosa</italic>, 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 <italic>S. aureus</italic> and Gram-negative <italic>P. aeruginosa</italic>, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of <italic>P. aeruginosa</italic> cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties.</p>