Trypanosomes, the pathogens of the Sleeping Sickness, cover their entire energy supply by glucose which they obtain in large quantities form our blood. In order to be able to ferment glucose, the parasite must first invest energy in the form of adenosine triphosphate (ATP). If ATP is consumed faster than it can be delivered this becomes fatal for the parasites.
Such metabolism-induced ‘burnout’ can be used for new forms of therapies, according to a study published in Science by an international research team with participation of Swiss TPH. In the case of Trypanosomes, glucose is fermented in a controlled way in a special cell organelle, the glycosome. The scientific team synthesized molecules that prevent the sugar degradation enzymes from entering the glycosome. As a result, the glucose is fermented uncontrolledly in the cell plasma and the entire supply of ATP is consumed. Thus, the glucose changes from the vital nutrient to a lethal poison for the trypanosomes. The process does not affect human cells, because they exploit glucose through other pathways.
„The core problem of antimicrobial drug research is to kill parasites without harming our own cells,” says Pascal Mäser, Swiss TPH. “This new approach kills the Trypanosomes very selectively and therefore offers great potential for new therapies”.