Rügen, NicolaiJenkins, Timothy P.Wielsch, NatalieVogel, HeikoHempel, Benjamin-FlorianSüssmuth, Roderich D.Ainsworth, StuartCabezas-Cruz, AlejandroVilcinskas, AndreasTonk, Miray2021-08-172021-08-172021-07-14https://depositonce.tu-berlin.de/handle/11303/13510http://dx.doi.org/10.14279/depositonce-12293Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.en570 Biowissenschaften; Biologieassassin bugsvenomtranscriptomicsproteomicsbioactivityparalysiscytolysisantibacterialneurolysisArticle2021-08-012227-9059