Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Malanovic, N; Leber, R; Schmuck, M; Kriechbaum, M; Cordfunke, RA; Drijfhout, JW; de Breij, A; Nibbering, PH; Kolb, D; Lohner, K.
Phospholipid-driven differences determine the action of the synthetic antimicrobial peptide OP-145 on Gram-positive bacterial and mammalian membrane model systems.
Biochim Biophys Acta. 2015; 1848(10 Pt A):2437-2447
Doi: 10.1016/j.bbamem.2015.07.010
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- Co-Autor*innen der Med Uni Graz
- Kolb Dagmar
- Leber Regina
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- Abstract:
- OP-145, a synthetic antimicrobial peptide developed from a screen of the human cathelicidin LL-37, displays strong antibacterial activities and is--at considerably higher concentrations--lytic to human cells. To obtain more insight into its actions, we investigated the interactions between OP-145 and liposomes composed of phosphatidylglycerol (PG) and phosphatidylcholine (PC), resembling bacterial and mammalian membranes, respectively. Circular dichroism analyses of OP-145 demonstrated a predominant α-helical conformation in the presence of both membrane mimics, indicating that the different membrane-perturbation mechanisms are not due to different secondary structures. Membrane thinning and formation of quasi-interdigitated lipid-peptide structures was observed in PG bilayers, while OP-145 led to disintegration of PC liposomes into disk-like micelles and bilayer sheets. Although OP-145 was capable of binding lipoteichoic acid and peptidoglycan, the presence of these bacterial cell wall components did not retain OP-145 and hence did not interfere with the activity of the peptide toward PG membranes. Furthermore, physiological Ca++ concentrations did neither influence the membrane activity of OP-145 in model systems nor the killing of Staphylococcus aureus. However, addition of OP-145 at physiological Ca++-concentrations to PG membranes, but not PC membranes, resulted in the formation of elongated enrolled structures similar to cochleate-like structures. In summary, phospholipid-driven differences in incorporation of OP-145 into the lipid bilayers govern the membrane activity of the peptide on bacterial and mammalian membrane mimics. Copyright © 2015. Published by Elsevier B.V.
- Find related publications in this database (using NLM MeSH Indexing)
- Anti-Bacterial Agents - chemistry
- Anti-Bacterial Agents - pharmacology
- Antimicrobial Cationic Peptides - chemistry
- Antimicrobial Cationic Peptides - pharmacology
- Cell Membrane Permeability - drug effects
- Cell Membrane Permeability - physiology
- Cell Survival - drug effects
- Cell Survival - physiology
- Humans -
- Lipid Bilayers - chemistry
- Phospholipids - chemistry
- Phospholipids - metabolism
- Staphylococcus aureus - drug effects
- Staphylococcus aureus - physiology
- Find related publications in this database (Keywords)
- Antibacterial activity
- Cytotoxicity
- Membrane mimics
- Membrane biophysics
- Lipoteichoic acid
- Peptidoglycan