Membrane morphology effects in quartz crystal microbalance characterization of antimicrobial peptide activity

Pandidan, Sara; Mechler, Ádám

doi:10.1016/j.bpc.2020.106381

Cited by 12 publications

(10 citation statements)

References 50 publications

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“…By contrast, colistin (128 μg/mL) showed a week fluorescence increase, similar to 4 μg/mL WRK-12. Consistently, membrane disruption has been suggested as one of crucial mechanisms of action for AMPs killing [ 38 ]. Besides, WRK-12 significantly dissipated membrane potential (ΔΨ) ( Figure 6 C), which was critical component of bacterial proton motive force [ 39 ].…”

Section: Resultsmentioning

confidence: 89%

Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

Shi

Tong

et al. 2020

Microorganisms

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The emergence and prevalence of multidrug-resistant (MDR) bacteria particularly Gram-negative bacteria presents a global crisis for human health. Colistin and tigecycline were recognized as the last resort of defenses against MDR Gram-negative pathogens. However, the emergence and prevalence of MCR or Tet(X)-mediated acquired drug resistance drastically impaired their clinical efficacy. It has been suggested that antimicrobial peptides might act a crucial role in combating antibiotic resistant bacteria owing to their multiple modes of action and characteristics that are not prone to developing drug resistance. Herein, we report a safe and stable tryptophan-rich amphiphilic peptide termed WRK-12 with broad-spectrum antibacterial activity against various MDR bacteria, including MRSA, colistin and tigecycline-resistant Escherichia coli. Mechanistical studies showed that WRK-12 killed resistant E. coli through permeabilizing the bacterial membrane, dissipating membrane potential and triggering the production of reactive oxygen species (ROS). Meanwhile, WRK-12 significantly inhibited the formation of an E. coli biofilm in a dose-dependent manner. These findings revealed that amphiphilic peptide WRK-12 is a promising drug candidate in the fight against MDR bacteria.

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Section: Resultsmentioning

confidence: 89%

Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

Shi

Tong

et al. 2020

Microorganisms

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“…It is expected that once EVs from various cancer cells can be produced in quantities suitable for the above structural studies, we will be able to see further insight into mechanistic details of membrane-active compounds and, in particular, identify which types of cell membranes have the highest affinity to bind certain ACPs, aiding the identification of their optimal application areas. Finally, not only the membrane model but also the assay conditions should be considered in studies on peptide-membrane interaction, as highlighted recently [20,[107][108][109][110]. In summary, with a critical view, the results presented here may provide a good assumption towards the in vivo action of the ACPs studied.…”

Section: High Helicity Non-inserted Perpendicular To Surfacementioning

confidence: 72%

Membrane Association Modes of Natural Anticancer Peptides: Mechanistic Details on Helicity, Orientation, and Surface Coverage

Quemé‐Peña

Juhász

Kohut

et al. 2021

IJMS

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Anticancer peptides (ACPs) could potentially offer many advantages over other cancer therapies. ACPs often target cell membranes, where their surface mechanism is coupled to a conformational change into helical structures. However, details on their binding are still unclear, which would be crucial to reach progress in connecting structural aspects to ACP action and to therapeutic developments. Here we investigated natural helical ACPs, Lasioglossin LL-III, Macropin 1, Temporin-La, FK-16, and LL-37, on model liposomes, and also on extracellular vesicles (EVs), with an outer leaflet composition similar to cancer cells. The combined simulations and experiments identified three distinct binding modes to the membranes. Firstly, a highly helical structure, lying mainly on the membrane surface; secondly, a similar, yet only partially helical structure with disordered regions; and thirdly, a helical monomeric form with a non-inserted perpendicular orientation relative to the membrane surface. The latter allows large swings of the helix while the N-terminal is anchored to the headgroup region. These results indicate that subtle differences in sequence and charge can result in altered binding modes. The first two modes could be part of the well-known carpet model mechanism, whereas the newly identified third mode could be an intermediate state, existing prior to membrane insertion.

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“…Besides that, specially designed helices such as syndiotactic helices were also studied. Different factors that can affect the activity of AMPs were investigated, such as AMP length, , net charge, helicity, solubility, the membrane morphology, the hydrophobicity of polar groups on lipids, and the blocking effect of lipopolysaccharide (LPS) on the outer membrane of Gram-negative bacterial membrane on the permeabilization of AMPs. , Food and Drug Administration (FDA) has approved 57 small peptide–drugs (with residue sequence shorter than 50) in the past 20 years. The majority of those peptides are receptor-binding peptides (65%), which function by binding with specific transmembrane receptors, thus affecting the signal transmitted to the innate immune system, and a small amount of membrane-active peptides (7%), which function by directly interacting with specific lipid membranes .…”

Section: Introductionmentioning

confidence: 99%

Interaction of Human β Defensin Type 3 (hBD-3) with Different PIP2-Containing Membranes, a Molecular Dynamics Simulation Study

Zhang

2021

J. Chem. Inf. Model.

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Human β defensin type 3 (hBD-3) is a cysteine-rich small antibacterial peptide. It belongs to the human innate immune system. hBD-3 has six cysteine residues, which form three pairs of disulfide bonds, and those bonds break in the reducing condition. It is known that hBD-3 can interact with bacterial membrane, and even eukaryotic cell membrane, which has a low concentration of phosphatidylinositol 4,5-bisphosphate (PIP2) lipids. PIP2 is a vital component in cell membranes and has been found to play important roles during antimicrobial peptide (AMP) interaction with membranes. To understand the functional mechanism of hBD-3 interacting with PIP2-containing membranes, the binding structures of hBD-3 on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers mixed with 10% of PIP2 were predicted using two kinds of methods. The first one is by placing the hBD-3 monomer in different orientations above the POPC + 10%PIP2 membrane to set up five different initial simulation systems and performing long-term simulations on each to predict the most stable binding structure. It was found that hBD-3 analogue binds on the mixed lipid membrane on the two loop regions. The second method is by running long-term simulations on one or nine hBD-3 dimers binding on POPC mixed with 10%PIP2 lipid bilayer starting from the solid-state NMR (ssNMR)-suggested orientation. The dimer dissociated, and the most stable binding of hBD-3 in wild-type on the mixed membrane is also through the two loop regions, which agrees with the prediction from both the first method and the lipid self-assembly result. The PIP2 lipids can form long-lasting hydrogen bonds with positively charged residues such as Arg and Lys on hBD-3, thus forming clusters with hBD-3. As a comparison, hBD-3 dimers binding with a combined bilayer having 1,2-palmitoyl-oleoyl-sn-glycero-3-phosphoserine (POPS) on the upper and POPC on the lower leaflets and the combined POPS + POPC bilayer mixing with 10%PIP2 were also studied. The long-term simulation result shows that hBD-3 can bind with the heads of negatively charged POPS and PIP2 lipids and form hydrogen bonds. The stable binding sites of hBD-3 on PIP2 or POPS mixed bilayers are still on the two loop regions. On the combined POPS + POPC mixed with 10%PIP2 bilayer, the binding of hBD-3 with PIP2 lipids became less stable and fewer because of the competition of binding with the POPS lipids. Besides that, binding with hBD-3 can decrease the membrane thickness of the POPC + PIP2, POPS + POPC, and POPS + POPC + PIP2 bilayers and make POPS and PIP2 lipids more flexible based on the order parameter calculations. Our results supply molecular insight on AMP binding with different membranes and can help understand the functional mechanism of hBD-3 disrupting PIP2-containing membranes.

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Membrane morphology effects in quartz crystal microbalance characterization of antimicrobial peptide activity

Cited by 12 publications

References 50 publications

Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

Membrane Association Modes of Natural Anticancer Peptides: Mechanistic Details on Helicity, Orientation, and Surface Coverage

Interaction of Human β Defensin Type 3 (hBD-3) with Different PIP2-Containing Membranes, a Molecular Dynamics Simulation Study

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