Kapishnikov, S.; Staalsø, T.; Yang, Y.; Lee, J.; Pérez-Berná, A. J.; Pereiro, E.; Werner, S.; Guttmann, P.; Leiserowitz, L.; Als-Nielsen, J.: The in-vivo Mode of Action of Quinoline Antimalarial Drugs Unveiled by X-ray Microscopy. Microscopy and Microanalysis 26 (2020), p. 3004-3006
10.1017/S1431927620023508
Open Accesn Version
Abstract:
Emerging resistance of malaria-causing parasites Plasmodium to current drug treatments highlights the need for identifying efficient targets to improve antimalarial therapies. Malaria symptoms appear when Plasmodium parasites are released into the blood stream where they invade the red blood cells. Within a red blood cell the parasite consumes hemoglobin. Hemoglobin digestion liberates large quantities of heme, which is toxic to the parasite. The parasite detoxifies free heme by its crystallization into inert hemozoin that remains in the parasite and offers a docking surface for continuously supplied heme. Our recent study, based on soft X-ray cryo-tomography and X-ray fluorescence microscopy1 , indicates that hemoglobin digestion and hemozoin crystallization is an assembly line process, where the rates of heme liberation and heme crystallization obviously must match. Both processes occur in a single parasitic organelle called the digestive vacuole wherein large quantities of hemoglobin have been found.2 Therefore, if hemozoin crystal growth is severely retarded, this would result in accumulation of the toxic heme in the parasite leading to poisoning of the latter. One way to inhibit hemozoin crystal growth is by capping its surface with an appropriate molecule thereby reducing the number of available docking sites. This is a promising drug target