Article (Scientific journals)
De Novo Transcriptome Analysis of the Venom of Latrodectus geometricus with the Discovery of an Insect-Selective Na Channel Modulator.
Khamtorn, Pornsawan; Peigneur, Steve; Gobbi Amorim, Fernanda et al.
2022In Molecules, 27 (1), p. 47
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Keywords :
Latrodectus geometricus; insect sodium channels; ion channel; spider; toxin; transcriptome; venom; Proteome; Sodium Channel Agonists; Sodium Channels; Spider Venoms; Animals; Computational Biology; Databases, Genetic; Female; Gene Ontology; Proteomics/methods; Sodium Channels/genetics; Sodium Channels/metabolism; Spider Venoms/genetics; Spiders/genetics; Gene Expression Profiling; Transcriptome; Proteomics; Spiders; Analytical Chemistry; Chemistry (miscellaneous); Molecular Medicine; Pharmaceutical Science; Drug Discovery; Physical and Theoretical Chemistry; Organic Chemistry
Abstract :
[en] The brown widow spider, Latrodectus geometricus, is a predator of a variety of agricultural insects and is also hazardous for humans. Its venom is a true pharmacopeia representing neurotoxic peptides targeting the ion channels and/or receptors of both vertebrates and invertebrates. The lack of transcriptomic information, however, limits our knowledge of the diversity of components present in its venom. The purpose of this study was two-fold: (1) carry out a transcriptomic analysis of the venom, and (2) investigate the bioactivity of the venom using an electrophysiological bioassay. From 32,505 assembled transcripts, 8 toxin families were classified, and the ankyrin repeats (ANK), agatoxin, centipede toxin, ctenitoxin, lycotoxin, scorpion toxin-like, and SCP families were reported in the L. geometricus venom gland. The diversity of L. geometricus venom was also uncovered by the transcriptomics approach with the presence of defensins, chitinases, translationally controlled tumor proteins (TCTPs), leucine-rich proteins, serine proteases, and other important venom components. The venom was also chromatographically purified, and the activity contained in the fractions was investigated using an electrophysiological bioassay with the use of a voltage clamp on ion channels in order to find if the neurotoxic effects of the spider venom could be linked to a particular molecular target. The findings show that U24-ctenitoxin-Pn1a involves the inhibition of the insect sodium (Nav) channels, BgNav and DmNav. This study provides an overview of the molecular diversity of L. geometricus venom, which can be used as a reference for the venom of other spider species. The venom composition profile also increases our knowledge for the development of novel insecticides targeting voltage-gated sodium channels.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Khamtorn, Pornsawan;  Program in Research and Development in Pharmaceuticals, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Peigneur, Steve ;  Toxicology and Pharmacology, Campus Gasthuisberg, University of Leuven (KU Leuven), 3000 Leuven, Belgium
Gobbi Amorim, Fernanda  ;  Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Quinton, Loïc  ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique
Tytgat, Jan;  Toxicology and Pharmacology, Campus Gasthuisberg, University of Leuven (KU Leuven), 3000 Leuven, Belgium
Daduang, Sakda;  Center for Research and Development of Herbal Health Products (CDR-HHP), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand ; Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Khon Kaen University, Khon Kaen 40002, Thailand ; Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Language :
English
Title :
De Novo Transcriptome Analysis of the Venom of Latrodectus geometricus with the Discovery of an Insect-Selective Na Channel Modulator.
Publication date :
2022
Journal title :
Molecules
eISSN :
1420-3049
Publisher :
MDPI, Switzerland
Volume :
27
Issue :
1
Pages :
47
Peer reviewed :
Peer reviewed
Funding number :
Thailand Research Fund
Funding text :
GOE7120N, GOC2319N, and GOA4919N from the F.W.O. Vlaanderen, awarded to J.T. and S.P. was supported by KU Leuven funding (PDM/19/164) and F.W.O. Vlaanderen grant 12W7822N.Funding: This research was funded by The Thailand Research Fund, Royal Golden Jubilee Ph.D. program (PHD0104/2558) and was partially supported by the KKU Research Fund, fiscal year 2020 and Thailand Research Fund, grant number DBG6080006. This study was supported by grants
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