Interaction of an Antimicrobial Peptide with Membranes: Experiments and Simulations with NKCS

Gofman, Yana; Linser, Sebastian; Rzeszutek, Agnieszka; Shental-Bechor, Dalit; Funari, Sérgio S.; Ben‐Tal, Nir; Willumeit‐Römer, Regine

doi:10.1021/jp909154y

Cited by 13 publications

(12 citation statements)

References 63 publications

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“…Next, the peptide NKCS was tested against the model Gram-negative bacterium E. coli . NKCS appeared very active with a minimal inhibitory concentration (MIC) at 0.6 µM, which was the same as previously reported [ 30 ] ( Figure 1 b).…”

Section: Resultssupporting

confidence: 89%

“…In previous studies the peptide NKCS was shown to be very active against both Gram-negative and Gram-positive bacteria with insignificant toxicity towards human cells [ 28 , 30 ]. These biological characteristics make it an interesting and potent candidate as a novel antibacterial agent, and suggest it as a model for understanding AMP interaction with bacterial membranes.…”

Section: Resultsmentioning

confidence: 99%

“…NKCS was derived from NK-2 by replacement of the cysteine at position 7 by serine, what yielded a more stable peptide, which is resistant to oxidation. Previous circular dichroism experiments revealed that the peptide is randomly coiled in aqueous solution, but adopts an α-helical structure in an hydrophobic environment [ 30 ]. Moreover, Monte Carlo simulations suggested that NKCS does not form a rigid straight rod, but rather a helix-hinge-helix structure when binding to membranes [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes

et al. 2015

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NKCS is an improved mutant of the bioactive peptide NK-2, which shows strong activity against Escherichia coli and low toxicity towards human cells. The different activity demonstrates the relevance of the physico-chemical nature of the target membrane for the biological effect of this peptide. We studied the effect of this potent antimicrobial peptide on model membranes by activity studies, differential scanning calorimetry, single molecule tracking and tracer efflux experiments. We found that NKCS severely distorted, penetrated and perforated model lipid membranes that resembled bacterial membranes, but not those that were similar to human cell membranes. The interactions of NKCS with phosphatidylethanolamine, which is abundant in bacterial membranes, were especially strong and are probably responsible for its antimicrobial activity.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes

et al. 2015

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“…Notably, rEP should be able to adopt different conformations depending on the surrounding microenvironment and experimental conditions. Moreover, Gram-negative bacteria contain moderate amounts of anionic lipids (below 20%) in their outer and cytoplasmic membranes, whereas the cytoplasmic membrane of Gram-positive bacteria is rich in anionic lipids (more than 50%) [35]. We saw that the antimicrobial activity of rEP was proportional to its helical structure, irrespective of its composition and overall negative charge.…”

Section: Plos Onementioning

confidence: 88%

Dietary supplementation of recombinant antimicrobial peptide Epinephelus lanceolatus piscidin improves growth performance and immune response in Gallus gallus domesticus

et al. 2020

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Supplementing chicken feed with antibiotics can improve survival and prevent disease outbreaks. However, overuse of antibiotics may promote the development of antibiotic-resistant bacteria. Recently, antimicrobial peptides have been proposed as alternatives to antibiotics in animal husbandry. Here, we evaluate the effects of antimicrobial peptide, Epinephelus lanceolatus piscidin (EP), in Gallus gallus domesticus. The gene encoding EP was isolated, sequenced, codon-optimized and cloned into a Pichia pastoris recombinant protein expression system. The expressed recombinant EP (rEP) was then used as a dietary supplement for G. g. domesticus; overall health, growth performance and immunity were assessed. Supernatant from rEP-expressing yeast showed in vitro antimicrobial activity against Grampositive and Gram-negative bacteria, according to an inhibition-zone diameter (mm) assay. Moreover, the antimicrobial peptide function of rEP was temperature independent. The fermentation broth yielded a spray-dried powder formulation containing 262.9 μg EP/g powder, and LC-MS/MS (tandem MS) analysis confirmed that rEP had a molecular weight of 4279 Da, as expected for the 34-amino acid peptide; the DNA sequence of the expression vector was also validated. We then evaluated rEP as a feed additive for G. g. domesticus. Treatment groups included control, basal diet and rEP at different doses (0.75, 1.5, 3.0, 6.0 and 12%). Compared to control, rEP supplementation increased G. g. domesticus weight gain, feed efficiency, IL-10 and IFN-γ production. Our results suggest that crude rEP could provide an alternative to traditional antibiotic feed additives for G. g. domesticus, serving to enhance growth and health of the animals.

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“…Our group developed a model that performs Monte Carlo (MC) simulations of the interaction of helical peptides with lipid bilayers. The simulation model has been tested on a variety of antimicrobial peptides, including magainin2 (6), penetratin (6), melittin (7), NKCS (8) and novicidin (9). These studies have furthered our understanding of the action mechanisms and selectivity of the antimicrobial peptides.…”

Section: Introductionmentioning

confidence: 99%

Monte Carlo simulations of peptide-membrane interactions with the MCPep web server

Gofman

Haliloğlu

Ben‐Tal

2012

Nucleic Acids Research

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The MCPep server (http://bental.tau.ac.il/MCPep/) is designed for non-experts wishing to perform Monte Carlo (MC) simulations of helical peptides in association with lipid membranes. MCPep is a web implementation of a previously developed MC simulation model. The model has been tested on a variety of peptides and protein fragments. The simulations successfully reproduced available empirical data and provided new molecular insights, such as the preferred locations of peptides in the membrane and the contribution of individual amino acids to membrane association. MCPep simulates the peptide in the aqueous phase and membrane environments, both described implicitly. In the former, the peptide is subjected solely to internal conformational changes, and in the latter, each MC cycle includes additional external rigid body rotational and translational motions to allow the peptide to change its location in the membrane. The server can explore the interaction of helical peptides of any amino-acid composition with membranes of various lipid compositions. Given the peptide’s sequence or structure and the natural width and surface charge of the membrane, MCPep reports the main determinants of peptide–membrane interactions, e.g. average location and orientation in the membrane, free energy of membrane association and the peptide’s helical content. Snapshots of example simulations are also provided.

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Interaction of an Antimicrobial Peptide with Membranes: Experiments and Simulations with NKCS

Cited by 13 publications

References 63 publications

NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes

NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes

Dietary supplementation of recombinant antimicrobial peptide Epinephelus lanceolatus piscidin improves growth performance and immune response in Gallus gallus domesticus

Monte Carlo simulations of peptide-membrane interactions with the MCPep web server

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