Toxins from remipede crabs found in Mexican caves may have significant pharmacological potential, according to a study published in BMC Biology.
Many animals use venoms for protection or hunting. Certain chemicals in these venoms — toxins — interfere with physiological processes, making them interesting for developing new pharmacological agents.
While the venoms of snakes, spiders, scorpions, and insects are well-known, this is not the case with marine animals. For these animals, there is data for some specific animal species, but the composition of many venoms is largely unknown, meaning this could still hold great untapped potential.
A few years ago, researchers also discovered venomous crustaceans. These animals, called remipedes, look like centipedes and live in marine underwater caves. A research team led by Dr. Björn von Reumont, who described the venom system in remipedes in 2014, is now working on a group of toxins from the Xibalbanus tulumensis remipede. Von Reumont works with a team from the Fraunhofer Institute for Translational Medicine (ITMP) and the Universities of Leuven, Cologne, Berlin, and Munich.
This remipede lives in underwater cave systems on the Mexican Yucatan peninsula. When hunting, it injects the venom produced in its venom gland directly into its prey. This venom contains various components, including a new type of peptide, xibalbine.
Some of these xibalbines contain a special structural element similar to other toxins, particularly those produced by spiders: several amino acids (cysteines) are bound to each other in such a manner that they form a knot-like structure. This makes the peptides highly resistant to enzymatic degradation, heat, and even extreme pH values. In spiders, these knottins act as neurotoxins and paralyze prey. Von Reumont’s team believes remipedes’ xibalbines can do the same.
The study shows that all the xibalbine peptides tested – in particular Xib1, Xib2 and Xib13– effectively blocked potassium channels in mammalian systems. “This inhibition is greatly important when it comes to developing drugs for a range of neurological diseases, including epilepsy,” said von Reumont. Xib1 and Xib13 can also inhibit voltage-gated sodium channels, such as those found in nerve or heart muscle cells. Furthermore, Xib1 and Xib13 can activate two specific proteins called kinases PKA-II and ERK1/2, which are involved in signal transduction in neurons. This suggests they may be involved in pain sensitization, which opens up new approaches in pain therapy.
Although the team recognises the potential of this discovery, the production of any drugs from animal venoms is a complex and time-consuming process, and it’s still many years away. “Finding suitable candidates and comprehensively characterizing their effects, thus laying the foundation for safe and effective drugs, is only possible today in a large interdisciplinary team, as in the case of our study,” said von Reumont.
Making matters more difficult is the fact that the remipedes’ habitat is under threat from the construction of the Tren Maya intercity railroad network, which cuts straight through the Yucatan Peninsula. “The cenotes are a highly sensitive ecosystem,” explained von Reumont. “Our study highlights the importance of protecting biodiversity, not only for its ecological significance but also for potential substances that could be of crucial importance to us humans.”
Pinheiro-Junior, E.L., Alirahimi, E., Peigneur, S. et al. Diversely evolved xibalbin variants from remipede venom inhibit potassium channels and activate PKA-II and Erk1/2 signaling. BMC Biol 22, 164 (2024). https://doi.org/10.1186/s12915-024-01955-5