Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum.
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 30 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.
Department of Chemistry and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA.
Rebecca G
RG
Marvin
Janet L
JL
Wolford
Matthew J
MJ
Kidd
Sean
S
Murphy
Jesse
J
Ward
Emily L
EL
Que
Meghan L
ML
Mayer
James E
JE
Penner-Hahn
Kasturi
K
Haldar
Thomas V
TV
O'Halloran
D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D056004:Molecular Dynamics Simulation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
D015032:Zinc