1. Selective antibacterial activity of the cationic peptide PaDBS1R6 against Gram-negative bacteria
- Author
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Fensterseifer, Isabel C. M., Felício, Mário Romão, 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., and Repositório da Universidade de Lisboa
- Subjects
Antimicrobial peptide (AMP) ,Antibiotic resistance ,Pseudomonas aeruginosa ,Escherichia coli ,PaDBS1R6 ,Drug design ,Joker algorithm - Abstract
© 2019 Elsevier B.V. All rights reserved., 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., This work was supported by Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) project PTDC/BBB-BQB/3494/2014, Marie Skłodowska-Curie Research and Innovation Staff Exchange (MSCA-RISE, European Union) project INPACT (call H2020-MSCA-RISE-2014, grant agreement 644167), Ramon Areces Foundation (to CFN), DTRA (HDTRA1-15-1-0050 to TKL), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2016/24413-0 to MDTT), Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG # 201710267000062 to ESFA) and Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF). MRF acknowledges FCT-MCTES fellowship SFRH/BD/100517/2014. ONS holds a postdoctoral scholarship from National Council of Technological and Scientific Development (CNPq) and Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT) – Brazil [300583/2016-8]. MHC acknowledges fellowship 141518/2015-4 (CNPq) and 88881.134423/2016-01 (CAPES).
- Published
- 2019