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“…In contrast, bombinin in combination with feleucin-BV1 produced a clear synergistic effect. In view of the high degree of structural diversity of AMPs in amphibian defensive skin secretions and the widely held view that such secretions, like venoms, act in a holistic manner through numerous intermolecular interactions, it would not be surprising to observe such cooperative effects and, indeed, this has been previously reported for the magainins from Xenopus skin [1–9, 24]. Although the feleucins are among the smallest amphibian skin AMPs, recently, an AMP consisting of 8 amino acid residues—FFFLSRIFa—and named temporin-SHf was reported from the skin of the North African ranid frog, Pelophylax saharica [25].…”
Section: Discussionmentioning
confidence: 75%
“…It remains unclear whether AMPs in these complex defensive skin secretions act on their own or cooperate/interact with others. Early studies on AMPs from African clawed frog ( Xenopus laevis ) skin suggested that cooperative effects did in fact occur between different peptides [24]. In view of this, it was decided to investigate possible synergistic actions between the novel bombinin and the feleucins using a standard checkerboard assay [20, 21].…”
The first amphibian skin antimicrobial peptide (AMP) to be identified was named bombinin, reflecting its origin from the skin of the European yellow-bellied toad (Bombina variegata). Bombinins and their related peptides, the bombinin Hs, were subsequently reported from other bombinid toads. Molecular cloning of bombinin-encoding cDNAs from skin found that bombinins and bombinin Hs were coencoded on the same precursor proteins. Here, we report the molecular cloning of two novel cDNAs from a skin secretion-derived cDNA library of B. variegata whose open-reading frames each encode a novel bombinin (GIGGALLNVGKVALKGLAKGLAEHFANamide) and a C-terminally located single copy of a novel nonapeptide (FLGLLGGLLamide or FLGLIGSLLamide). These novel nonapeptides were named feleucin-BV1 and feleucin-BV2, respectively. The novel bombinin exhibited 89% identity to homologues from the toads, B. microdeladigitora and B. maxima. The feleucins exhibited no identity with any amphibian AMP archived in databases. Synthetic feleucins exhibited a weak activity against Staphylococcus aureus (128–256 mg/L) but feleucin-BV1 exhibited a synergistic action with the novel bombinin. The present report clearly demonstrates that the skin secretions of bombinid toads continue to represent a source of peptides of novel structure that could provide templates for the design of therapeutics.
“…In contrast, bombinin in combination with feleucin-BV1 produced a clear synergistic effect. In view of the high degree of structural diversity of AMPs in amphibian defensive skin secretions and the widely held view that such secretions, like venoms, act in a holistic manner through numerous intermolecular interactions, it would not be surprising to observe such cooperative effects and, indeed, this has been previously reported for the magainins from Xenopus skin [1–9, 24]. Although the feleucins are among the smallest amphibian skin AMPs, recently, an AMP consisting of 8 amino acid residues—FFFLSRIFa—and named temporin-SHf was reported from the skin of the North African ranid frog, Pelophylax saharica [25].…”
Section: Discussionmentioning
confidence: 75%
“…It remains unclear whether AMPs in these complex defensive skin secretions act on their own or cooperate/interact with others. Early studies on AMPs from African clawed frog ( Xenopus laevis ) skin suggested that cooperative effects did in fact occur between different peptides [24]. In view of this, it was decided to investigate possible synergistic actions between the novel bombinin and the feleucins using a standard checkerboard assay [20, 21].…”
The first amphibian skin antimicrobial peptide (AMP) to be identified was named bombinin, reflecting its origin from the skin of the European yellow-bellied toad (Bombina variegata). Bombinins and their related peptides, the bombinin Hs, were subsequently reported from other bombinid toads. Molecular cloning of bombinin-encoding cDNAs from skin found that bombinins and bombinin Hs were coencoded on the same precursor proteins. Here, we report the molecular cloning of two novel cDNAs from a skin secretion-derived cDNA library of B. variegata whose open-reading frames each encode a novel bombinin (GIGGALLNVGKVALKGLAKGLAEHFANamide) and a C-terminally located single copy of a novel nonapeptide (FLGLLGGLLamide or FLGLIGSLLamide). These novel nonapeptides were named feleucin-BV1 and feleucin-BV2, respectively. The novel bombinin exhibited 89% identity to homologues from the toads, B. microdeladigitora and B. maxima. The feleucins exhibited no identity with any amphibian AMP archived in databases. Synthetic feleucins exhibited a weak activity against Staphylococcus aureus (128–256 mg/L) but feleucin-BV1 exhibited a synergistic action with the novel bombinin. The present report clearly demonstrates that the skin secretions of bombinid toads continue to represent a source of peptides of novel structure that could provide templates for the design of therapeutics.
“…These distinct mechanisms may be advantageous to the animal, since a larger choice implies in a defense mechanism that is efficient against different pathogens [38–40]. The conjoint action of these mechanisms promoted by the simultaneous secretion of different peptides can even lead to a more robust defense system [41, 42]. Interestingly the pore formation capacities of the three ocellatins correlate directly to their antimicrobial and hemolytic activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2.Fig.…”
BackgroundThe availability of antimicrobial peptides from several different natural sources has opened an avenue for the discovery of new biologically active molecules. To the best of our knowledge, only two peptides isolated from the frog Leptodactylus labyrinthicus, namely pentadactylin and ocellatin-F1, have shown antimicrobial activities. Therefore, in order to explore the antimicrobial potential of this species, we have investigated the biological activities and membrane interactions of three peptides isolated from the anuran skin secretion.MethodsThree peptide primary structures were determined by automated Edman degradation. These sequences were prepared by solid-phase synthesis and submitted to activity assays against gram-positive and gram-negative bacteria and against two fungal strains. The hemolytic properties of the peptides were also investigated in assays with rabbit blood erythrocytes. The conformational preferences of the peptides and their membrane interactions have been investigated by circular dichroism spectroscopy and liposome dye release assays.ResultsThe amino acid compositions of three ocellatins were determined and the sequences exhibit 100% homology for the first 22 residues (ocellatin-LB1 sequence). Ocellatin-LB2 carries an extra Asn residue and ocellatin-F1 extra Asn-Lys-Leu residues at C-terminus. Ocellatin-F1 presents a stronger antibiotic potential and a broader spectrum of activities compared to the other peptides. The membrane interactions and pore formation capacities of the peptides correlate directly with their antimicrobial activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. All peptides acquire high helical contents in membrane environments. However, ocellatin-F1 shows in average stronger helical propensities.ConclusionsThe obtained results indicate that the three extra amino acid residues at the ocellatin-F1 C-terminus play an important role in promoting stronger peptide-membrane interactions and antimicrobial properties. The extra Asn-23 residue present in ocellatin-LB2 sequence seems to decrease its antimicrobial potential and the strength of the peptide-membrane interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-017-0094-y) contains supplementary material, which is available to authorized users.
“…Mag2 also exhibits such behavior, albeit the threshold concentration of tilting is much higher than PGLa (Strandberg et al, 2013), as its smaller hydrophobic sector compared to PGLa prevents Mag2 from deeper insertion into the bilayer (Figure 1B). Interestingly, PGLa and Mag2 together exhibit a synergistically enhanced antimicrobial activity (Westerhoff et al, 1995; Strandberg et al, 2015), and PGLa is able to insert in an upright position into the membrane (I-state) in the presence of Mag2 (Tremouilhac et al, 2006; Strandberg et al, 2013). To examine a correlation between this synergy and any modulation of membrane thickness, we also studied the mixture of these two peptides.…”
Membrane thinning has been discussed as a fundamental mechanism by which antimicrobial peptides can perturb cellular membranes. To understand which factors play a role in this process, we compared several amphipathic peptides with different structures, sizes and functions in their influence on the lipid bilayer thickness. PGLa and magainin 2 from X. laevis were studied as typical representatives of antimicrobial cationic amphipathic α-helices. A 1:1 mixture of these peptides, which is known to possess synergistically enhanced activity, allowed us to evaluate whether and how this synergistic interaction correlates with changes in membrane thickness. Other systems investigated here include the α-helical stress-response peptide TisB from E. coli (which forms membrane-spanning dimers), as well as gramicidin S from A. migulanus (a natural antibiotic), and BP100 (designer-made antimicrobial and cell penetrating peptide). The latter two are very short, with a circular β-pleated and a compact α-helical structure, respectively. Solid-state 2H-NMR and grazing incidence small angle X-ray scattering (GISAXS) on oriented phospholipid bilayers were used as complementary techniques to access the hydrophobic thickness as well as the bilayer-bilayer repeat distance including the water layer in between. This way, we found that magainin 2, gramicidin S, and BP100 induced membrane thinning, as expected for amphiphilic peptides residing in the polar/apolar interface of the bilayer. PGLa, on the other hand, decreased the hydrophobic thickness only at very high peptide:lipid ratios, and did not change the bilayer-bilayer repeat distance. TisB even caused an increase in the hydrophobic thickness and repeat distance. When reconstituted as a mixture, PGLa and magainin 2 showed a moderate thinning effect which was less than that of magainin 2 alone, hence their synergistically enhanced activity does not seem to correlate with a modulation of membrane thickness. Overall, the absence of a typical thinning response in the case of PGLa, and the increase in the repeat distance and membrane thickening observed for TisB, demonstrate that the concept of peptide-induced membrane thinning cannot be generalized. Instead, these results suggest that different factors contribute to the resulting changes in membrane thickness, such as the peptide orientation in the bilayer, and/or bilayer adaptation to hydrophobic mismatch.
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