1. Selective antibacterial activity of the cationic peptide PaDBS1R6 against Gram-negative bacteria.
- Author
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Fensterseifer ICM, Felício MR, Alves ESF, Cardoso MH, Torres MDT, Matos CO, Silva ON, Lu TK, Freire MV, Neves NC, Gonçalves S, Lião LM, Santos NC, Porto WF, de la Fuente-Nunez C, and Franco OL
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Antimicrobial Cationic Peptides pharmacology, Gram-Negative Bacteria drug effects
- Abstract
Infections caused by Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa foremost among them, constitute a major worldwide health problem. Bioinformatics methodologies are being used to rationally design new antimicrobial peptides, a potential alternative for treating these infections. One of the algorithms used to develop antimicrobial peptides is the Joker, which was used to design the peptide PaDBS1R6. This study evaluates the antibacterial activities of PaDBS1R6 in vitro and in vivo, characterizes the peptide interaction to target membranes, and investigates the PaDBS1R6 structure in contact with mimetic vesicles. Moreover, we demonstrate that PaDBS1R6 exhibits selective antimicrobial activity against Gram-negative bacteria. In the presence of negatively charged and zwitterionic lipids the structural arrangement of PaDBS1R6 transits from random coil to α-helix, as characterized by circular dichroism. The tertiary structure of PaDBS1R6 was determined by NMR in zwitterionic dodecylphosphocholine (DPC) micelles. In conclusion, PaDBS1R6 is a candidate for the treatment of nosocomial infections caused by Gram-negative bacteria, as template for producing other antimicrobial agents., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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