Details

Autor(en) / Beteiligte

• Irazazabal, Luz N.
• Porto, William F.
• Fensterseifer, Isabel C.M.
• Alves, Eliane S.F.
• Matos, Carolina O.
• Menezes, Antônio C.S.
• Felício, Mário R.
• Gonçalves, Sónia
• Santos, Nuno C.
• Ribeiro, Suzana M.
• Humblot, Vincent
• Lião, Luciano M.
• Ladram, Ali
• Franco, Octavio L.

Titel

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

Ist Teil von

• Biochimica et biophysica acta. Biomembranes, 2019-01, Vol.1861 (1), p.178-190

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •PaDBS1R1 has a broad spectrum of antimicrobial activity.•PaDBS1R1 kills bacteria within 5 min.•PaDBS1R1 adopts an α-helix structure on hydrophobic environments.