Revealing the Bioactivities of Physalia physalis Venom Using Drosophila as a Model

<i>Physalia physalis</i>, commonly known as the Portuguese Man o' War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of <i>P. physalis</i> venom by assessing its behavioral and toxicological effects on <i>Drosophila melanogaster</i>. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications.