De Novo Transcriptome Analysis of the Venom of Latrodectus geometricus with the Discovery of an Insect-Selective Na Channel Modulator

Molecules

Sakda Daduang¹  Fernanda Gobbi Amorim²  Loïc Quinton²  Pornsawan Khamtorn³  Jan Tytgat⁴  Steve Peigneur⁴ 

[1] Center for Research and Development of Herbal Health Products (CDR-HHP), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand;Laboratory of Mass Spectrometry, MolSys Research Unit, Department of Chemistry, University of Liège, 4000 Liège, Belgium;Program in Research and Development in Pharmaceuticals, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand;Toxicology and Pharmacology, Campus Gasthuisberg, University of Leuven (KU Leuven), 3000 Leuven, Belgium;

关键词: transcriptome;    Latrodectus geometricus;    venom;    toxin;    spider;    ion channel;   

DOI  :  10.3390/molecules27010047

来源: DOAJ

【 摘 要 】

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 (Na_v) channels, BgNa_v and DmNa_v. 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.

【 授权许可】

Unknown