Parabutoporin, a cationic amphipathic peptide from scorpion venom: Much more than an antibiotic

Remijsen, Quinten; Verdonck, Fons

doi:10.1016/j.toxicon.2009.10.027

Cited by 36 publications

(24 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cationic peptides may destabilize membranes at a given concentration (Remijsen et al, 2010), but the mechanism of action of some of them is still unclear (Jenssen et al, 2006; Mookherjee and Hancock, 2007). Parabutoporin is an example of scorpion cationic amphipathic lysine-rich and cysteine-free peptide with antimicrobial, antifungal and immunoregulatory activities (Remijsen et al, 2010). In silico and circular dichroism analyses of seven antifungal NDBPs highlighted the relevance of cationicity and amphipathicity for their antimicrobial activity (Guilhelmelli et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

et al. 2017

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A. nidulans, A. niger, A. terreus, Neurospora crassa, Penicillium corylophilum, P. ochrochloron, P. verrucosum, P. viridicatum, P. waksmanii, and Talaromyces flavus) was evaluated by quantitative microplate reader assay. Tsv (100 and 500 μg/well, which correspond to 1 and 5 mg/mL, respectively, of total soluble protein) was active in inhibiting growth of A. nidulans, A. terreus, P. corylophilum, and P. verrucosum, especially in the higher concentration used and at the first 30 h. After this period, fungi might have used Tsv components as alternative sources of nutrients, and therefore, increased their growth tax. Only fractions IX, X, XI, XIIA, XIIB (3 and 7.5 μg/well, which correspond to 30 and 75 μg/mL, respectively, of total soluble protein) and Ts1 (1.5, 3, and 6 μg/well, which correspond to 2.18, 4.36, and 8.72 μM, respectively) showed antifungal activity. Ts1 showed to be a non-morphogenic toxin with dose-dependent activity against A. nidulans, inhibiting 100% of fungal growth from 3 μg/well (4.36 μM). The inhibitory effect of Ts1 against A. nidulans growth was accompanied by fungistatic effects and was not amended by 1 mM CaCl2 or tetrodotoxin (46.98 and 93.96 μM). The structural differences between Ts1 and drosomycin, a potent cysteine-rich antifungal peptide, are discussed here. Our results highlight the antifungal potential of the first cysteine-containing scorpion toxin. Since Ts1 is a multifunctional toxin, we suggest that it could be used as a template in the design of engineered scorpion AMPs and in the search for new mechanisms of action of antifungal drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The venoms contain a molecular arsenal of different toxins that can be considered as a true combinatorial library of peptides with diversified biological activites such as anti-cancer (Dardevet et al, 2015), antimicrobial (Torres-Larios et al, 2000; Luna-Ramirez et al, 2013; Harrison et al, 2014), antiviral (Yan et al, 2011; Chen et al, 2012), antimalarial (Conde et al, 2000; Carballar-Lejarazu et al, 2008), immune-modulatory (Gurrola et al, 2012; Remijsen et al, 2010; Varga et al, 2012), anti-epilepsy (Wang et al, 2001) and bradykinin potentiating components (Almaaytah and Albalas, 2014). In fact, these toxins/peptides have been extensively exploited as a source of specific probes and potential therapeutic molecules for their targeting proteins, e.g.…”

Section: Introductionmentioning

confidence: 99%

Recombinant expression of Intrepicalcin from the scorpion Vaejovis intrepidus and its effect on skeletal ryanodine receptors

Vargas-Jaimes

Liang

Zhang

et al. 2017

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Background Scorpion venoms contain toxins that modulate ionic channels, among which are the calcins, a small group of short, basic peptides with an Inhibitor Cystine Knot (ICK) motif that target calcium release channels/ryanodine receptors (RyRs) with high affinity and selectivity. Here we describe the heterologous expression of Intrepicalcin, identified by transcriptomic analysis of venomous glands from Vaejovis intrepidus. Methods Recombinant Intrepicalcin was obtained in Escherichia coli BL21-DE3 (periplasm) by fusing the intrepicalcin gene to sequences coding for signal-peptide, thioredoxin, His-tag and enterokinase cleavage site. Results [3H]Ryanodine binding, used as a functional index of RyR activity, revealed that recombinant Intrepicalcin activates skeletal RyR (RyR1) dose-dependently with Kd = 17.4 ± 4.0 nM. Intrepicalcin significantly augments the bell-shaped [Ca2+]-[3H]ryanodine binding curve at all [Ca2+] ranges, as is characteristic of the calcins. In single channel recordings, Intrepicalcin induces the appearance of a subconductance state in RyR1 with a fractional value ~55% of the full conductance state, very close to that of Vejocalcin. Furthermore, Intrepicalcin stimulates Ca2+ release at an initial dose = 45.3 ± 2.5 nM, and depletes ~50% of Ca2+ load from skeletal sarcoplasmic reticulum vesicles. Conclusions We conclude that active recombinant Intrepicalcin was successfully obtained without the need of manual oxidation, enabling it to target RyR1s with high affinity. General Significance This is the first calcin heterologously expressed in the periplasma of Escherichia coli BL21-DE3, shown to be pharmacologically effective, thus paving the way for the generation of Intrepicalcin variants that are required for structure-function relationship studies of calcins and RyRs.

show abstract

“…30 Regardless of their role in the ecology of venom use, most functionally characterized scorpion-venom NDPs display antibiotic activities, oen concomitant with signicant cytolytic action that limits their potential therapeutic application. 13,30,31 More recently, a number of synthetic variants of some of these peptides have been designed in which the cytolytic action against mammalian cells (mainly tested in hemolytic assays) has been reduced, while the antimicrobial effect of the native peptide has been preserved (see, for example, ref. 32 and 33).…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

“…37 An intriguing feature of some scorpion-venom AMPs is their ability to affect mammalian cells at non-lytic concentrations, as exemplied by the NDP Parbutoporin from Parabuthus schlechteri, which promotes neutrophil chemotaxis and degranulation while delaying spontaneous neutrophil apoptosis. 31 In this sense, scorpion-venom AMPs are not different from mammalian host defense peptides, now recognized as not "merely antimicrobials", but important signaling molecules of the innate immune defense system. 29 Such features broaden the scope of potential applications of scorpion-venom AMPs; however, much research is still needed to clarify their precise molecular targets and mechanism of action.…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

CHAPTER 7. Scorpion Venoms as a Platform for Drug Development

Vega¹,

Corzo²,

Possani³

2015

Drug Discovery

View full text Add to dashboard Cite

Parabutoporin, a cationic amphipathic peptide from scorpion venom: Much more than an antibiotic

Cited by 36 publications

References 61 publications

Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

Recombinant expression of Intrepicalcin from the scorpion Vaejovis intrepidus and its effect on skeletal ryanodine receptors

CHAPTER 7. Scorpion Venoms as a Platform for Drug Development

Contact Info

Product

Resources

About