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

Abstract

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.

An Unusual Two-Domain Thyropin from Tick Saliva: NMR Solution Structure and Highly Selective Inhibition of Cysteine Cathepsins Modulated by Glycosaminoglycans

“…In this context, cathepsins V, K, and L targeted by IrThy are known to be involved in the immune response and inflammation and are also present in the host skin [48][49][50][51][52][53]. Another clue to the potential physiological function of IrThy comes from a recent report on U24-ctenitoxin-Pn1a, a neurotoxin found in spider venom, that targets voltage-gated sodium channels (VGSCs) [54]. Interestingly, this protein contains two tandem Tg1 domains and is a close homolog of IrThy.…”

A history of accidental widow spider (genus Latrodectus ) introductions on the island of Ireland with a new irish record for Latrodectus hesperus (Chamberlin and Ivie, 1935), and additional records of Latrodectus geometricus (C.L. Koch, 1841).

“…The genus Latrodectus contains several species of medical importance (Almeida et al 2009;Clark et al 1992;Garb et al 2004;Khamtorn et al 2022). With the introduction of Latrodectus species to new environments comes the novel risk of human envenoming.…”

“…S. nobilis shares over 60% of its venom repertoire with Latrodectus and envenoming by S. nobilis and S. grossa can present latrodectism-like symptoms (Dunbar et al 2020;Graudins et al 2002). Latrodectus geometricus shares more of its venom components with S. nobilis than L. hesperus (Khamtorn et al 2022). To date, there have been no human deaths resulting from envenoming by S. nobilis or L. geometricus.…”

“…Both have established populations outside of their native ranges by exploiting urban structures and synanthropic habitats (Kulczycki et al 2012;Sadir and Marske 2021;Vetter et al 2015;. Additionally, both have similar venom compositions and are responsible for occasional, comparatively severe envenoming cases (Khamtorn et al 2022). Thus, the question can be posed whether the recent establishment and continuing spread of S. nobilis in Ireland and the consequent increase in envenoming rates, could possibly be replicated by a species such as L. geometricus.…”

“…In Ireland and Britain, there are 19 genera of combfooted spiders (Araneae: Theridiidae) encompassing 58 native and non-native species (Bee et al 2020). Of the identified non-native species, those from the subfamily Latrodectinae (Petrunkevitch, 1928) known as 'false' widows (genus Steatoda Sundevall, 1833) are closely related to the highly potent 'true' widows (genus Latrodectus Walckenaer, 1805) (Daly et al 2001), and are also of known medical significance (Dunbar et al 2018a;Dunbar et al 2020;Dunbar et al 2022b;Isbister and Gray 2003;Khamtorn et al 2022). In Ireland, four species of Steatoda have been recorded: Steatoda nobilis (Thorell, 1875), Steatoda grossa (C.L.…”