Selective antibacterial activity of the cationic peptide PaDBS1R6 against Gram-negative bacteria

Selective antibacterial activity of the cationic peptide PaDBS1R6 against Gram-negative bacteria

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 infection...

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Published in:Biochimica et biophysica acta. Biomembranes Vol. 1861; no. 7; pp. 1375 - 1387
Main Authors: Fensterseifer, Isabel C.M., Felício, Mário R., Alves, Eliane S.F., Cardoso, Marlon H., Torres, Marcelo D.T., Matos, Carolina O., Silva, Osmar N., Lu, Timothy K., Freire, Maurício V., Neves, Natan C., Gonçalves, Sónia, Lião, Luciano M., Santos, Nuno C., Porto, William F., de la Fuente-Nunez, Cesar, Franco, Octavio L.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-07-2019
Elsevier
Subjects:
Animals
Anti-Bacterial Agents - pharmacology
Antibiotic resistance
Antimicrobial Cationic Peptides - pharmacology
Antimicrobial peptide (AMP)
Drug design
Escherichia coli
Gram-Negative Bacteria - drug effects
Joker algorithm
Mice
Mice, Inbred C57BL
Microbial Sensitivity Tests
PaDBS1R6
Pseudomonas aeruginosa
Joker algorithm
Escherichia coli
Antibiotic resistance
Antimicrobial peptide (AMP)
Pseudomonas aeruginosa
Drug design
PaDBS1R6
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Summary: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. [Display omitted] •PaDBS1R6 presented in-helix conformation when in contact with anionic lipid membranes•Antibacterial selectivity of PaDBS1R6 against Gram-negative bacteria•PaDBS1R6 was active in vivo in murine intraperitoneal and skin infection models.
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ISSN:0005-2736
1879-2642
DOI:10.1016/j.bbamem.2019.03.016