Determining the pharmacological potential and biological role of linear pseudoscorpion toxins via functional profiling
Pelin Erkoc,
Susanne Schiffmann,
Thomas Ulshöfer,
Marina Henke,
Michael Marner,
Jonas Krämer,
Reinhard Predel,
Till F. Schäberle,
Sabine Hurka,
Ludwig Dersch,
Andreas Vilcinskas,
Robert Fürst,
Tim Lüddecke
Affiliations
Pelin Erkoc
Institute of Pharmaceutical Biology, Faculty of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt, 60438 Frankfurt, Germany; LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany
Susanne Schiffmann
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), 60596 Frankfurt, Germany
Thomas Ulshöfer
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), 60596 Frankfurt, Germany
Marina Henke
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), 60596 Frankfurt, Germany
Michael Marner
Branch of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME-BR), 35392 Giessen, Germany
Jonas Krämer
Institute of Zoology, University of Cologne, Zuelpicher Strasse 47b, 50674 Cologne, Germany; Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26–32, 35392 Giessen, Germany
Reinhard Predel
Institute of Zoology, University of Cologne, Zuelpicher Strasse 47b, 50674 Cologne, Germany
Till F. Schäberle
Branch of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME-BR), 35392 Giessen, Germany; Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26–32, 35392 Giessen, Germany; German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Ohlebergsweg 12, 35392 Giessen, Germany
Sabine Hurka
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Branch of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME-BR), 35392 Giessen, Germany
Ludwig Dersch
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Branch of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME-BR), 35392 Giessen, Germany
Andreas Vilcinskas
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Branch of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME-BR), 35392 Giessen, Germany; Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26–32, 35392 Giessen, Germany
Robert Fürst
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Pharmaceutical Biology, Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 Munich, Germany; Corresponding author
Tim Lüddecke
LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany; Branch of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME-BR), 35392 Giessen, Germany; Corresponding author
Summary: Arthropod venoms contain bioactive molecules attractive for biomedical applications. However, few of these have been isolated, and only a tiny number has been characterized. Pseudoscorpions are small arachnids whose venom has been largely overlooked. Here, we present the first structural and functional assessment of the checacin toxin family, discovered in the venom of the house pseudoscorpion (Chelifer cancroides). We combined in silico and in vitro analyses to establish their bioactivity profile against microbes and various cell lines. This revealed inhibitory effects against bacteria and fungi. We observed cytotoxicity against specific cell types and effects involving second messengers. Our work provides insight into the biomedical potential and evolution of pseudoscorpion venoms. We propose that plesiotypic checacins evolved to defend the venom gland against infection, whereas apotypic descendants evolved additional functions. Our work highlights the importance of considering small and neglected species in biodiscovery programs.
