Plasmodium yoelii iron transporter PyDMT1 interacts with host ferritin and is required in full activity for malarial pathogenesis

Author:

Zhong Mengjiao,Zhou BingORCID

Abstract

Abstract Background The rapid reproduction of malaria parasites requires proper iron uptake. However, the process of iron absorption by parasites is rarely studied. Divalent metal transporter (DMT1) is a critical iron transporter responsible for uptaking iron. A homolog of human DMT1 exists in the malaria parasite genome, which in Plasmodium yoelii is hereafter named PyDMT1. Results PyDMT1 knockout appears to be lethal. Surprisingly, despite dwelling in an iron-rich environment, the parasite cannot afford to lose even partial expression of PyDMT1; PyDMT1 hypomorphs were associated with severe growth defects and quick loss of pathogenicity. Iron supplementation could completely suppress the defect of the PyDMT1 hypomorph during in vitro culturing. Genetic manipulation through host ferritin (Fth1) knockout to increase intracellular iron levels enforced significant growth inhibition in vivo on the normal parasites but not the mutant. In vitro culturing with isolated ferritin knockout mouse erythrocytes completely rescued PyDMT1-hypomorph parasites. Conclusion A critical iron requirement of malaria parasites at the blood stage as mediated by this newly identified iron importer PyDMT1, and the iron homeostasis in malarial parasites is finely tuned. Tipping the iron balance between the parasite and host will efficiently kill the pathogenicity of the parasite. Lastly, PyDMT1 hypomorph parasites were less sensitive to the action of artemisinin.

Funder

National Basic Research Program of China

National Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Developmental Biology,Plant Science,General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Physiology,Ecology, Evolution, Behavior and Systematics,Structural Biology,Biotechnology

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