Phenylalanine residues act as membrane anchors in the antimicrobial action of Aurein 1.2

Shahmiri, Mahdi; Cornell, Bruce; Mechler, Ádám

doi:10.1116/1.4995674

Cited by 29 publications

(26 citation statements)

References 48 publications

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“…www.nature.com/scientificreports/ activity of these transpeptidases, the d-alanine sequences present in the β-lactams impair the formation of the bacterial cell wall, consequently inducing bacterial death. In addition, it has been demonstrated that residues of phenylalanine in a very small antimicrobial peptide denoted Aurein 1.2, are involved in its initial binding to the membrane and act as anchors 39 .…”

Section: Discussionmentioning

confidence: 99%

A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains

Marques

Franzolin

Sanabani

et al. 2020

Sci Rep

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Many studies have linked the antimicrobial properties of kefir with the presence of bacteriocins and organic acids. In the present work, results obtained from bacteriostatic and bactericidal studies, and from RP-HPLC, Mass Spectrometry and proton NMR analysis, show that a sample of milk kefir grains is able to produce an antimicrobial fraction, denoted FK-1000, composed of sugars and amino acids, predominantly polymers of alanine, doublets of tyrosine and phenylalanine. Since this fraction is a lyophilized product whose molecular profile is different from bacteriocins and simple carboxylic acids, its antimicrobial effect cannot be attributed to these molecules, or to alcohols or hydrogen peroxide. The fraction is bactericidal against weak-acid-resistant MRSA and weak-acid resistant P. aeruginosa at pH 5, and is bacteriostatic against both pathogens at pH 7. In combination formulation, the FK-1000 fraction is able to increase fivefold the effect of streptomycin against P. aeruginosa and it is not toxic to human epithelial cells at antimicrobial concentrations. 16 S rRNA microbiota analysis of antimicrobial-producing and non-producing kefir grains demonstrated that they are distinct. In summary, the results indicate that milk kefir grains can produce different classes of molecules with potent antibiotic activity against resistant bacteria.

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Section: Discussionmentioning

confidence: 99%

A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains

Marques

Franzolin

Sanabani

et al. 2020

Sci Rep

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“…It is believed that α-helicity of this highly amphipathic peptide is the result of a templating process, between the lipid headgroup and tail zone, where the hydrophobic residues align to the membrane core and the hydrophilic residues are exposed to water (25). From the fact that aurein1.2-NH-CH 3 is not becoming α-helical at all in the presence of membranes one can speculate that the peptide is not entering even the headgroup zone of the membrane, the weak binding seen in QCM is likely caused by loose surface association and/or a local change of buffer viscosity due to the presence of the peptides (26).…”

Section: Discussionmentioning

confidence: 99%

The role of C-terminal amidation in the mechanism of action of the antimicrobial peptide aurein 1.2

Shahmiri

Mechler

2020

The EuroBiotech Journal

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C-terminal amidation is a common feature of wild type membrane disrupting antimicrobial peptides (AMPs). Empirical evidence suggests that this modification increases antimicrobial efficacy. However, the actual role of C-terminal amidation in the molecular mechanism of action of AMPs is not fully understood. Amidation alters two key properties simultaneously: the net charge and helicity of the peptide, both of which are implicated in the mechanism of action. However, the differences between the physicochemical properties of the carboxyl and amide moieties have been disregarded in former studies. In this study we assessed whether the difference in activity is only caused by changes in the helicity and overall charge of a peptide, i.e. whether the chemistry of the terminus is otherwise irrelevant. To do so, the membrane disrupting activity of a modified aurein 1.2 peptide was studied in which a secondary amide was formed with a terminal methyl group, instead of the primary amide as in the wild type peptide. Results of quartz crystal microbalance, dye leakage and circular dichroism experiments show that the activity of the modified peptide is substantially reduced compared to the wild type peptide, in particular that the modified peptide exhibited a much-reduced ability to bind to the membrane. Thus, the primary amide at the C-terminus is required to bind to the membrane, and a secondary amide cannot serve the same purpose. We hypothesize that this difference is related to the hydration state of the terminus. The lack of membrane binding ability of the modified peptide identifies the primary amide moiety at the C terminus as a specific membrane binding motif.

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“…On one hand, this offers a great therapeutic potential. The incorporation of Phe residues has indeed demonstrated to drastically increase the potency of antimicrobial peptides plausibly by enabling stronger interaction with the bacterial cell envelope [ 7 , 8 ]. On the other hand, the propensity of Phe for the membrane hydrocarbon core together with its tendency to cluster has been implicated in metabolic and neurological disorders [ 6 , 9 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Phenylalanine intercalation parameters for liquid-disordered phase domains – a membrane model study

Adamczewski

Tsoukanova

2018

BMC Biophys

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BackgroundPropensity of phenylalanine (Phe) for nonpolar environments drives its intercalation into phospholipid membranes, which has been implicated in metabolic and neurological disorders. The knowledge of Phe intercalation parameters can be instrumental in understanding various membrane processes triggered by interactions with Phe, in particular the early events leading to the formation of nucleation/docking sites for the self-assembly of Phe amyloid fibrils at the membrane surface.ResultsIn this study, we used monolayers of phosphatidylethanolamine (DPPE) and phosphatidylcholine (DPPC) to mimic the membrane outer leaflet. Its initial interaction with Phe was modeled by injecting Phe into the aqueous phase underneath the monolayer. Constant pressure insertion assays augmented with epifluorescence microscopy imaging were used to monitor Phe intercalation. Our primary goal was to determine the Phe intercalation area, APhe. Two values were obtained for APhe, 33 ± 2 and 48 ± 3 Å2.ConclusionsPhe appeared to discriminate between DPPE and DPPC packing, and use two modes of intercalation. The area of APhe 33 ± 2 Å2 is consistent with a Phe monomer intercalating into membrane by inserting the phenyl ring nearly normal to the membrane surface. This mode has been found to operate in DPPE membranes. For DPPC membranes however, the value of APhe = 48 ± 3 Å2 suggests that, from saline, Phe tends to intercalate as a larger species plausibly dragging along a counterion, Na+, in a Na+(Phe) complex.Electronic supplementary materialThe online version of this article (10.1186/s13628-018-0047-z) contains supplementary material, which is available to authorized users.

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Phenylalanine residues act as membrane anchors in the antimicrobial action of Aurein 1.2

Cited by 29 publications

References 48 publications

A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains

A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains

The role of C-terminal amidation in the mechanism of action of the antimicrobial peptide aurein 1.2

Phenylalanine intercalation parameters for liquid-disordered phase domains – a membrane model study

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