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

Isabel C M Fensterseifer; Mário R Felício; Eliane S F Alves; Marlon H Cardoso; Marcelo D T Torres; Carolina O Matos; Osmar N Silva; Timothy K Lu; Maurício V Freire; Natan C Neves; Sónia Gonçalves; Luciano M Lião; Nuno C Santos; William F Porto; Cesar de la Fuente-Nunez; Octavio L Franco

doi:10.1016/j.bbamem.2019.03.016

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

Biochim Biophys Acta Biomembr. 2019 Jul 1;1861(7):1375-1387. doi: 10.1016/j.bbamem.2019.03.016. Epub 2019 Mar 26.

Authors

Isabel C M Fensterseifer¹, Mário R Felício², Eliane S F Alves³, Marlon H Cardoso⁴, Marcelo D T Torres⁵, Carolina O Matos³, Osmar N Silva⁶, Timothy K Lu⁷, Maurício V Freire⁸, Natan C Neves⁸, Sónia Gonçalves², Luciano M Lião³, Nuno C Santos², William F Porto⁹, Cesar de la Fuente-Nunez¹⁰, Octavio L Franco¹¹

Affiliations

¹ Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil; Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, DF, Brazil.
² Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
³ Laboratório de RMN, Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, Brazil.
⁴ Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil; Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, DF, Brazil; S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.
⁵ Departments of Psychiatry and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
⁶ S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.
⁷ Synthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Research Laboratory of Electronics, Department of Biological Engineering, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil.
⁹ S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil; Porto Reports, Brasília-DF, Brazil.
¹⁰ Departments of Psychiatry and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. Electronic address: cfuente@pennmedicine.upenn.edu.
¹¹ Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil; Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, DF, Brazil; S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil. Electronic address: ocfranco@gmail.com.

PMID: 30926365
DOI: 10.1016/j.bbamem.2019.03.016

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.

Keywords: Antibiotic resistance; Antimicrobial peptide (AMP); Drug design; Escherichia coli; Joker algorithm; PaDBS1R6; Pseudomonas aeruginosa.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology*
Antimicrobial Cationic Peptides / pharmacology*
Gram-Negative Bacteria / drug effects*
Mice
Mice, Inbred C57BL
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides