RT info:eu-repo/semantics/article T1 Divergence in toxin antigenicity and venom enzymes in Tityus melici, a medically important scorpion, despite transcriptomic and phylogenetic affinities with problematic Brazilian species A1 Kalapothakis, Yan A1 Miranda, Kelton A1 Aragão, Matheus A1 Larangote, Débora A1 Braga Pereira, Gracielle A1 Noetzold, Marina A1 Molina, Denis A1 Langer, Rafael A1 Mamede Conceição, Izabela A1 Guerra Duarte, Clara A1 Chávez Olórtegui, Carlos A1 Kalapothakis, Evanguedes A1 Borges Strauss, Adolfo A2 Centro para el Desarrollo de la Investigación Científica AB The Brazilian scorpion Tityus melici, native to Minas Gerais and Bahia, is morphologically related to Tityus serrulatus, the most medically significant species in Brazil. Despite inhabiting scorpion-envenomation endemic regions, T. melici venom remains unexplored. This work evaluates T. melici venom composition and function using transcriptomics, enzymatic activities, and in vivo and in vitro immunological analyses. Next-Generation Sequencing unveiled 86 components putatively involved in venom toxicity: 39 toxins, 28 metalloproteases, seven disulfide isomerases, six hyaluronidases, three phospholipases and three amidating enzymes. T. serrulatus showed the highest number of toxin matches with 80–100 % sequence similarity. T. melici is of medical importance as it has a venom LD50 of 0.85 mg/kg in mice. We demonstrated venom phospholipase A2 activity, and elevated hyaluronidase and metalloprotease activities compared to T. serrulatus, paralleling our transcriptomic findings. Comparison of transcriptional levels for T. serrulatus and T. melici venom metalloenzymes suggests species-specific expression patterns in Tityus. Despite close phylogenetic association with T. serrulatus inferred from COI sequences and toxin similarities, partial neutralization of T. melici venom toxicity was achieved when using the anti-T. serrulatus antivenom, implying antigenic divergence among their toxins. We suggest that the Brazilian therapeutic scorpion antivenom could be improved to effectively neutralize T. melici venom. PB Elsevier SN 0141-8130 YR 2024 FD 2024-02-23 LK http://hdl.handle.net/20.500.14066/4394 UL http://hdl.handle.net/20.500.14066/4394 LA eng NO Kalapothakis, Y., Miranda, K., Aragão, M., Larangote, D., Braga-Pereira, G., Noetzold, M., Molina, D., Langer, R., Conceição, I. M., Guerra-Duarte, C., Chávez-Olórtegui, C., Kalapothakis, E., & Borges, A. (2024). Divergence in toxin antigenicity and venom enzymes in Tityus melici, a medically important scorpion, despite transcriptomic and phylogenetic affinities with problematic Brazilian species. International Journal of Biological Macromolecules, 263(Pt 2), Artículo 130311. https://doi.org/10.1016/j.ijbiomac.2024.130311 NO Corresponding author at: Centro para el Desarrollo de la Investigación Científica, CEDIC, Asunción 1255, Paraguay. Adolfo Borges, borges.adolfo@gmail.com NO Consejo Nacional de Ciencia y Tecnología DS MINDS@UW RD 15-may-2024