The Dual Prey-Inactivation Strategy of Spiders—In-Depth Venomic Analysis of Cupiennius salei

Most knowledge of spider venom concerns neurotoxins acting on ion channels, whereasproteins and their significance for the envenomation process are neglected. The here presentedcomprehensive analysis of the venom gland transcriptome and proteome ofCupiennius saleifocusses on proteins and cysteine-containing peptides and offers new insight into the structureand function of spider venom, here described as the dual prey-inactivation strategy. After venominjection, many enzymes and proteins, dominated byα-amylase, angiotensin-converting enzyme,and cysteine-rich secretory proteins, interact with main metabolic pathways, leading to a majordisturbance of the cellular homeostasis. Hyaluronidase and cytolytic peptides destroy tissue andmembranes, thus supporting the spread of other venom compounds. We detected 81 transcripts ofneurotoxins from 13 peptide families, whereof two families comprise 93.7% of all cysteine-containingpeptides. This raises the question of the importance of the other low-expressed peptide families.The identification of a venom gland-specific defensin-like peptide and an aga-toxin-like peptide inthe hemocytes offers an important clue on the recruitment and neofunctionalization of body proteinsand peptides as the origin of toxins.