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, whereas proteins and their significance for the envenomation process are neglected. The here presented comprehensive analysis of the venom gland transcriptome and proteome of Cupiennius salei focusses on proteins and cysteine-containing peptides and offers new insight into the structure and function of spider venom, here described as the dual prey-inactivation strategy. After venom injection, many enzymes and proteins, dominated by α-amylase, angiotensin-converting enzyme, and cysteine-rich secretory proteins, interact with main metabolic pathways, leading to a major disturbance of the cellular homeostasis. Hyaluronidase and cytolytic peptides destroy tissue and membranes, thus supporting the spread of other venom compounds. We detected 81 transcripts of neurotoxins from 13 peptide families, whereof two families comprise 93.7% of all cysteine-containing peptides. 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 in the hemocytes offers an important clue on the recruitment and neofunctionalization of body proteins and peptides as the origin of toxins.