DEVELOPMENT OF A MALDI-MASS SPECTROMETRY IMAGING METHOD TO UNDERSTAND THE NECROTIC MECHANISMS OF SNAKE ENVENOMATION

With an estimated 81,000 to 138,000 deaths per year, snakebite envenomation has been considered a neglected tropical disease by the WHO since 2017. This method exploits MALDI-Mass Spectrometry Imaging (MALDI-MSI) to understand tissue alteration and necrosis mechanisms after envenomation. Snake venom, a complex mix of peptides, proteins and enzymes mainly targets the nervous and neuromuscular systems, with some causing local tissue necrosis. Key protein toxins responsible for cytotoxicity are PLA2s (Phospholipases A2) and SVMPs (Snake Venom Metalloproteinases). PLA2s (10-20 kDa) cleave cell membrane, causing necrosis at the bite site, while SVMPs (20-100 kDa) hydrolyze basement membrane proteins and alter cell adhesion.
This method uses MALDI-MSI to visualize the action of synthetic or purified toxins like PLA2s and SVMPs, crude venoms, and HPLC-separated venoms on murine tissues, to understand the necrotic mechanisms and pave the way for new treatments.