Analogous venom peptides acting on different pathways: a study of Bicarinalin and U₉-MYRTX-Tb1a from T. bicarinatum venom

For decades venom were studied for various applications as agriculture, therapeutics or as pharmacological tools. Currently, six venom-derived drugs and one venom-derived insecticide are available on market. Ant venoms exhibit a high diversity of peptides, similarly to other arthropod venoms. The first studies shown many in vitro and in vivo biological effects such as anti-microbial, anti-inflammatory, anti-viral or even ion channel modulators. Our study focused on M-MYRTX-Tb1a (Bicarinalin) and U₉-MYRTX-Tb1a, two peptides from Tetramorium bicarinatum venom exhibiting similar sequences. Bicarinalin is an amphipatic α-helical peptide, which was found to forms pores in cell membranes. As the sequence of U₉-MYRTX-Tb1a suggests a similar structure with identical physico-chemical properties, we hypothesized a similar biological function. In this study we investigated the biological effect of U₉-MYRTX-Tb1a. We tested the two peptides on Drosophila melanogaster embryonic cells to evaluate their cytotoxicity. As predicted, the Drosophila cells lysis was observed with the addition of both peptides. However, the cell morphology after peptide incubation and the time-effect was different between U₉-MYRTX-Tb1a and Bicarinalin suggesting different mechanisms of action. First, incubation with U₉-MYRTX-Tb1a leads to cell growing, and blebs forming with a potential condensation of the nucleus. Then, the cytotoxicity effect of Bicarinalin is faster than the U₉-MYRTX-Tb1a. These first results, suggest that pro-apoptotic and/or autophagic pathways could be involved in biological activity of U₉-MYRTX-Tb1a. By confirming this hypothesis, we could update the first peptide from ant venom with a pro-apoptotic and/or autophagic effect and the various associated applications.