Fast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide

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dc.creatorIrazazabal, Luz Noemí
dc.creatorPorto, William Farias
dc.creatorFensterseifer, Isabel Cristina Marques
dc.creatorAlves, Eliane Santana Fernandes
dc.creatorMatos, Carolina Oliveira
dc.creatorMenezes, Antônio Severo
dc.creatorFelício, Mário Romão
dc.creatorGonçalves, Sónia
dc.creatorSantos, Nuno C.
dc.creatorRibeiro, Suzana Meira
dc.creatorHumblot, Vincent
dc.creatorLiao, Luciano Morais
dc.creatorLadram, Ali
dc.creatorFranco, Octávio Luiz
dc.date.accessioned2024-02-21T11:30:48Z
dc.date.available2024-02-21T11:30:48Z
dc.date.issued2019
dc.description.abstractAntimicrobial 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.citationIRAZAZABAL, 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.doi10.1016/j.bbamem.2018.08.001
dc.identifier.issn0005-2736
dc.identifier.issne- 1879-2642
dc.identifier.urihttp://repositorio.bc.ufg.br//handle/ri/24397
dc.language.isoeng
dc.publisher.countryHolanda
dc.publisher.departmentInstituto de Química - IQ (RMG)
dc.rightsAcesso Aberto
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAntimicrobial peptides
dc.subjectRational design
dc.subjectMembrane permeabilization/depolarization
dc.subjectCircular dichroism (CD)
dc.subjectNuclear magnetic resonance (NMR)
dc.subjectElectron microscopy (EM)
dc.titleFast and potent bactericidal membrane lytic activity of PaDBS1R1, a novel cationic antimicrobial peptide
dc.typeArtigo

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