Spider Venom: Components, Modes of Action, and Novel Strategies in Transcriptomic and Proteomic Analyses

Abstract

This review gives an overview on the development of research on spider venoms with a focus on structure and function of venom components and techniques of analysis. Major venom component groups are small molecular mass compounds, antimicrobial (also called cytolytic, or cationic) peptides (only in some spider families), cysteine-rich (neurotoxic) peptides, and enzymes and proteins. Cysteine-rich peptides are reviewed with respect to various structural motifs, their targets (ion channels, membrane receptors), nomenclature, and molecular binding. We further describe the latest findings concerning the maturation of antimicrobial, and cysteine-rich peptides that are in most known cases expressed as propeptide-containing precursors. Today, venom research, increasingly employs transcriptomic and mass spectrometric techniques. Pros and cons of venom gland transcriptome analysis with Sanger, 454, and Illumina sequencing are discussed and an overview on so far published transcriptome studies is given. In this respect, we also discuss the only recently described cross contamination arising from multiplexing in Illumina sequencing and its possible impacts on venom studies. High throughput mass spectrometric analysis of venom proteomes (bottom-up, top-down) are reviewed.

A Multiomics Approach Unravels New Toxins With Possible In Silico Antimicrobial, Antiviral, and Antitumoral Activities in the Venom of Acanthoscurria rondoniae

“…Spider venoms are composed of a complex mixture of salts, nucleotides and other small molecules, as well as bioactive molecules such as proteins and peptides, usually referred to as toxins (Escoubas and Rash, 2004;Kuhn-Nentwig et al, 2011;Langenegger et al, 2019). In spiders, toxins are produced and stored in venom glands.…”

“…The advances in sensitivity and resolution of mass spectrometers as well as advances in DNA and RNA sequencing techniques have led to a remarkable increase in the number of toxins reported in the last years (Duan et al, 2013;Sanggaard et al, 2014;Zelanis and Keiji Tashima, 2014;Abreu et al, 2017;Zobel-Thropp et al, 2018;Langenegger et al, 2019). However, the increase in toxin identification is not synchronized with the functional description of new toxins, since the functional characterization involves a significant number of experimental processes.…”

An Economic Dilemma between Molecular Weapon Systems May Explain an Arachno-Atypical Venom in Wasp Spiders (Argiope bruennichi)

“…Spider venoms tend to be chemically more complex than other animal venoms, and up to 3000 different venom components can be present in a single species [12,13]. It has been estimated that the sum of all spider venoms could ultimately yield 10 million bioactive molecules, but only 0.02% of this diversity has been discovered thus far [14,15].…”

An economic dilemma between weapon systems may explain an arachno-atypical venom in wasp spiders (Argiope bruennichi)

“…Spider venoms tend to be chemically more complex than other animal venoms and up to 1000 different venom components can be present in a single species (Herzig, 2019;Langenegger et al, 2019). It has been estimated, that the sum of all spider venoms could ultimately yield 10 million bioactive molecules, but only 0.02% of this diversity has been discovered thus far (Pineda et al, 2018;Lüddecke et al, 2019).…”

“…Several promising drug candidates for stroke, pain, cancer and neural disorders have been identified in spider venoms (Osteen et al, 2016;Chassagnon et al, 2017;Richards et al, 2018;Wu et al, 2019). The major components of these spider venoms are low molecular weight inhibitor cysteine knot (ICK) peptides with robust tertiary structures conferred by the presence of a pseudoknot motif of interweaved disulfide bonds (Pallaghy et al, 1994;Norton and Pallaghy, 1998;Langenegger et al, 2019). Also described as knottins, such peptides are often neurotoxic and remarkably resistant to heat, osmotic stress and enzymatic digestion, making them ideal drug candidates .…”