Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide
dc.creator | Irazazabal, Luz Noemí | |
dc.creator | Porto, William Farias | |
dc.creator | Fensterseifer, Isabel Cristina Marques | |
dc.creator | Alves, Eliane Santana Fernandes | |
dc.creator | Matos, Carolina Oliveira | |
dc.creator | Menezes, Antônio Severo | |
dc.creator | Felício, Mário Romão | |
dc.creator | Gonçalves, Sónia | |
dc.creator | Santos, Nuno C. | |
dc.creator | Ribeiro, Suzana Meira | |
dc.creator | Humblot, Vincent | |
dc.creator | Liao, Luciano Morais | |
dc.creator | Ladram, Ali | |
dc.creator | Franco, Octávio Luiz | |
dc.date.accessioned | 2024-02-21T11:30:48Z | |
dc.date.available | 2024-02-21T11:30:48Z | |
dc.date.issued | 2019 | |
dc.description.abstract | Antimicrobial peptides (AMPs) are promising candidates for the development of future antibiotics. In an attempt to increase the efficacy of therapeutic AMPs, computer-based design methods appear as a reliable strategy. In this study, we evaluated the antimicrobial efficiency and mechanism of action of a novel designed AMP named PaDBS1R1, previously designed by means of the Joker algorithm, using a fragment of the ribosomal protein L39E from the archaeon Pyrobaculum aerophilum as a template. PaDBS1R1 displayed low micromolar broad-spectrum antimicrobial activity against Gram-negative (MIC of 1.5 μM) and Gram-positive (MIC of 3 μM) bacteria, including carbapenem-resistant Klebsiella pneumoniae (MIC of 6.25 μM) and methicillin-resistant Staphylococcus aureus (MIC of 12.5 μM), without cytotoxicity towards HEK-293 cells. In addition, membrane permeabilization and depolarization assays, combined with time-kill studies and FEG-SEM imaging, indicated a fast membrane permeation and further leakage of intracellular content. Biophysical studies with lipid vesicles show a preference of PaDBS1R1 for Gram-negative bacteria-like membranes. We investigated the three-dimensional structure of PaDBS1R1 by CD and NMR analyses. Our results suggest that PaDBS1R1 adopts an amphipathic α-helix upon interacting with hydrophobic environments, after an initial electrostatic interaction with negative charges, suggesting a membrane lytic effect. This study reveals that PaDBS1R1 has potential application in antibiotic therapy. | |
dc.identifier.citation | IRAZAZABAL, Luz N. et al. Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide. BBA: biomembranes, Amsterdam, v. 1861, n. 1, p. 178-190, 2019. DOI: 10.1016/j.bbamem.2018.08.001. Disponível em: https://www.sciencedirect.com/science/article/pii/S0005273618302323?via%3Dihub. Acesso em: 16 fev. 2024. | |
dc.identifier.doi | 10.1016/j.bbamem.2018.08.001 | |
dc.identifier.issn | 0005-2736 | |
dc.identifier.issn | e- 1879-2642 | |
dc.identifier.uri | http://repositorio.bc.ufg.br//handle/ri/24397 | |
dc.language.iso | eng | |
dc.publisher.country | Holanda | |
dc.publisher.department | Instituto de Química - IQ (RMG) | |
dc.rights | Acesso Aberto | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Antimicrobial peptides | |
dc.subject | Rational design | |
dc.subject | Membrane permeabilization/depolarization | |
dc.subject | Circular dichroism (CD) | |
dc.subject | Nuclear magnetic resonance (NMR) | |
dc.subject | Electron microscopy (EM) | |
dc.title | Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide | |
dc.type | Artigo |
Arquivos
Pacote Original
1 - 1 de 1
Nenhuma Miniatura disponível
- Nome:
- Artigo - Luz Noemí Irazazabal - 2019.pdf
- Tamanho:
- 1.98 MB
- Formato:
- Adobe Portable Document Format
Licença do Pacote
1 - 1 de 1
Nenhuma Miniatura disponível
- Nome:
- license.txt
- Tamanho:
- 1.71 KB
- Formato:
- Item-specific license agreed upon to submission
- Descrição: