Structure and mode of action of the antimicrobial peptide arenicin

Andrä, Jörg; Jakovkin, Igor; Grötzinger, Joachim; Hecht, Oliver; Krasnosdembskaya, Anna D.; Goldmann, Torsten; Gutsmann, Thomas; Leippe, Matthias

doi:10.1042/bj20071051

Cited by 91 publications

(76 citation statements)

References 35 publications

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“…Hemolytic activity was evaluated as described previously by [25], with slight modification by [26]. A suspension of human erythrocytes was washed with phosphate buffered saline (PBS: 1.5 mM KH 2 PO 4 , 2.7 mM KCl, 8.1 mM Na 2 HPO 4 , 135 mM NaCl, pH 7.4) and then centrifuged at 6,000 × g for 10 min at least three times, until the supernatant was colorless.…”

Section: Hemolytic Activitymentioning

confidence: 99%

Use of Theobroma cacao Pod Husk-Derived Biofertilizer is Safe as it Poses neither Ecological nor Human Health Risks

Filho¹,

Carvalho-Silva²,

Sousa³

et al. 2017

J Fertil Pestic

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Cacao farmers use macerated Theobroma cacao pod husks as biofertilizer for restoration of environmentally important soil elements, i.e., N, P, K, Na, Mg, and Ca. The increasing popularity of this organic material for soil management justifies to experimentally ascertaining that its application does not produce environmental or human health risks. We therefore applied a battery of biological tests to assess possible health risks related to the extract of fermented cacao pod husks [CHE]. Minimal inhibitory concentration for selected bacteria and fungi was established and an antiviral assay (equine herpes virus -EHV-1) and insecticide assay (Aedes aegypti larvae), to observe possible environmental impact. Toxicity tests used Artemia salina, hemolytic activity and cytotoxicity were tested using HT-29 e Vero cells, respectively. Genotoxicity and anti-genotoxic activity was tested in the comet assay of leukocytes and a selection of Saccharomyces cerevisiae mutants allowed look for a possible interference of CHE with defined metabolic pathways. None of these established tests used to define toxicity and genotoxicity of chemical compounds indicated that CHE contained substances that would pose such risks. Our safety assessment on bacteria and yeasts, virus, insect larvae, and human leukocytes [3-(4,5-di-methylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and comet assay] thus indicated that macerated cocoa pod husk can be safely used as biofertilizer.

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Section: Hemolytic Activitymentioning

confidence: 99%

Use of Theobroma cacao Pod Husk-Derived Biofertilizer is Safe as it Poses neither Ecological nor Human Health Risks

Filho¹,

Carvalho-Silva²,

Sousa³

et al. 2017

J Fertil Pestic

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“…Arenicin-1 consists of two strands that form antiparallel b-sheets that are constrained by a disulfide bond and connected by a type I 0 b turn (Andrä et al 2008). This peptide shows considerable fungicidal effects against various human pathogenic fungal strains and acts by interacting with the membrane (Park and Lee 2009).…”

Section: Introductionmentioning

confidence: 99%

Membranolytic antifungal activity of arenicin-1 requires the N-terminal tryptophan and the beta-turn arginine

et al. 2010

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To determine the structural requirements of arenicin-1 in exerting antifungal activity, a truncated peptide with an N-terminal deletion and a peptide with an Ala substitution for an Arg in the beta-turn region were characterised by comparison to arenicin-1. The antifungal activities of the analogues were 25-50% lower than arenicin-1. Trp fluorescence and circular dichroism spectroscopy showed that Trp in the N-terminus contributed to peptide penetration and Arg in the beta-turn to conformational transition. These results suggest that Trp in the N-terminus and Arg in the beta-turn play a pivotal role in the membrane-directed antifungal activity of arenicin-1.

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“…It is non-hemolytic and very stable against tryptic digest. Moreover, it is particularly insensitive toward high salt concentration (10,28). In addition to the natural peptide, we used a linear form where two terminal cysteine residues have been replaced by serine (C/S-Ar-1) (28).…”

mentioning

confidence: 99%

Multiple Peptide Resistance Factor (MprF)-mediated Resistance of Staphylococcus aureus against Antimicrobial Peptides Coincides with a Modulated Peptide Interaction with Artificial Membranes Comprising Lysyl-Phosphatidylglycerol

Andrä

Goldmann

Ernst

et al. 2011

Journal of Biological Chemistry

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Modification of the membrane lipid phosphatidylglycerol (PG) of Staphylococcus aureus by enzymatic transfer of a L-lysine residue leading to lysyl-PG converts the net charge of PG from ؊1 to ؉1 and is thought to confer resistance to cationic antimicrobial peptides (AMPs). Lysyl-PG synthesis and translocation to the outer leaflet of the bacterial membrane are achieved by the membrane protein MprF. Consequently, mutants lacking a functional mprF gene are in particular vulnerable to the action of AMPs. Hence, we aim at elucidating whether and to which extent lysyl-PG modulates membrane binding, insertion, and permeabilization by various AMPs. Lysyl-PG was incorporated into artificial lipid bilayers, mimicking the cytoplasmic membrane of S. aureus. Moreover, we determined the activity of the peptides against a clinical isolate of S. aureus strain SA113 and two mutants lacking a functional mprF gene and visualized peptide-induced ultrastructural changes of bacteria by transmission electron microscopy. The studied peptides were: (i) NK-2, an ␣-helical fragment of mammalian NK-lysin, (ii) arenicin-1, a lugworm ␤-sheet peptide, and (iii) bee venom melittin. Biophysical data obtained by FRET spectroscopy, Fourier transform infrared spectroscopy, and electrical measurements with planar lipid bilayers were correlated with the biological activities of the peptides. They strongly support the hypothesis that peptide-membrane interactions are a prerequisite for eradication of S. aureus. However, degree and mode of modulation of membrane properties such as fluidity, capacitance, and conductivity were unique for each of the peptides. Altogether, our data support and underline the significance of lysyl-PG for S. aureus resistance to AMPs.

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Structure and mode of action of the antimicrobial peptide arenicin

Cited by 91 publications

References 35 publications

Use of Theobroma cacao Pod Husk-Derived Biofertilizer is Safe as it Poses neither Ecological nor Human Health Risks

Use of Theobroma cacao Pod Husk-Derived Biofertilizer is Safe as it Poses neither Ecological nor Human Health Risks

Membranolytic antifungal activity of arenicin-1 requires the N-terminal tryptophan and the beta-turn arginine

Multiple Peptide Resistance Factor (MprF)-mediated Resistance of Staphylococcus aureus against Antimicrobial Peptides Coincides with a Modulated Peptide Interaction with Artificial Membranes Comprising Lysyl-Phosphatidylglycerol

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