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"We have identified a whole catalog of new, exciting toxins and were able to show how the yellow sac spider can cause such painful poisonings," explains Dr. Tim Lüddecke, head of the working group 'Animal Venomics' at the Institute for Insect Biotechnology (formerly LOEWE-ZIB) of JLU Giessen and first author of the study published in the journal 'Communications Biology' at the end of October.

The yellow sac spider is the most venomous spider in Germany. Its bite can cause symptoms requiring medical treatment. Despite this, the venom cocktail of this spider has remained largely unknown until now. Researchers at Justus Liebig University Giessen (JLU) and the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) have now, for the first time, deciphered the venom of the yellow sac spider, gaining important insights into the evolution and pharmacology of its toxins.

The venom contains many components that attack cell structures – similar to bee venom – thus causing the strong local effects. "This is primarily due to a toxin type called CPTX and the enzyme phospholipase A2," says Lüddecke.

Through extensive comparative analyses of venoms from across the spider kingdom and using evolutionary reconstructions, the researchers were able to deduce that both toxins have undergone a complex evolutionary history. While the CPTX toxin family and its relatives arose early in the evolution of modern spiders and acquired their characteristic structure through gene fusion, significant amounts of phospholipase A2 are found only in the yellow sac spider.

 The scientists suspect that the pharmacological and structural similarity between the venom of the yellow sac spider and bee venom is due to their comparable biological function. "Unlike other spiders, the yellow sac spider primarily uses its venom to defend its brood," explains Lüddecke. "Bees and some other species also have classic defensive venoms. Apparently, evolution responds to comparable problems with similar biomolecular solutions, even though the respective species are not closely related."

This opens up new perspectives for the search for active ingredients. Until now, spider venom has been considered almost exclusively in the search for new lead structures for the treatment of neurological diseases. "However, the range of toxins in the yellow sac spider that attack cells suggests that they should also be evaluated in the future for active ingredients against cell-based diseases such as cancer," explains Lüddecke.

The publication in the specialist journal "Communications Biology"

Lüddecke, T., Hurka, S., Dresler, J. et al. Comparative venomics suggests an evolutionary adaption of spider venom from predation to defense. Commun Biol 8, 1496 (2025). https://doi.org/10.1038/s42003-025-09015-6