Insights into the discovery and intervention of metalloproteinase in marine hazardous jellyfish

The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish Chrysaora quinquecirrha at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish. Jellyfish are a typical toxic organism influenced by the changing marine environment, such as rising sea temperatures and eutrophication in the past thirty years, which have led to an explosive growth of jellyfish, resulting in significant decrease in fish populations and increase in stinging patients, known as the second largest disaster in the ocean. Toxins are the main hazardous materials for the health threat, where metalloproteinase, as the main component. Therefore, is of great significance for studying the types, quantities, and activities of metalloproteinase, especially exploring its potential inhibitor-tetracycline which showed relatively safety and applyed to patients, and corresponding mechanisms.