Fluxes in “Free” and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum

Abstract

Summary Dynamic fluxes in the concentration of ions and small molecules are fundamental features of cell signaling, differentiation and development. Similar roles for fluxes in transition metal concentrations are less well established. Here we show that massive zinc fluxes are essential in the infection cycle of an intracellular eukaryotic parasite. Using single cell quantitative imaging we show that growth of the blood-stage Plasmodium falciparum parasite requires acquisition of thirty million zinc atoms per erythrocyte before host cell rupture, corresponding to a 400% increase in total zinc concentration. Zinc accumulates in a freely available form in parasitophorous compartments outside the food vacuole, including mitochondria. Restriction of zinc availability via small molecule treatment causes a drop in mitochondrial membrane potential and severely inhibits parasite growth. Thus extraordinary zinc acquisition and trafficking are essential for parasite development.

Small, Highly Active DNAs That Hydrolyze DNA

“…Therefore, despite the suboptimal sequences and activities of the natural class I deoxribozyme variants, some organisms could suffer DNA damage due to the occasional formation of imperfect self-cleaving structures. Some cells naturally experience unusually high Zn 2+ concentrations at times, 35 which could increase genomic instability by such deoxyribozymes. Perhaps, some living systems that require DNAs to be cleaved during their life cycle have evolved to take advantage of the inherent ability of certain DNA sequences to form high-speed self-hydrolyzing deoxyribozymes.…”

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

“…Intoxication of zinc has also been suggested to be involved in another operation of the immune system by inhibiting the growth of phagocytosed microorganisms (39, 428), where ZnT and ZIP transporters may play a role, as observed for copper transporters (445). The involvement of zinc at the host-pathogen interface is complex (271) and represents a topic that requires greater focus in the future (145).…”

Antiplasmodial activity of targeted zinc(II)-dipicolylamine complexes

“…Zinc acquisition and trafficking are essential for parasite replication and a recent study demonstrated that decreasing zinc levels inhibited Plasmodium development. [32] Alternatively, ZnDPA binding may be destabilizing the parasite membrane or anionic DNA scaffold causing parasite death. The anionic iRBC membrane may also be targeted and disrupted which could inhibit the extracellular exit of parasites from host cells.…”