Uptake and metabolism of arginine impact Plasmodium development in the liver

Patricia Meireles (1) , Antonio M. Mendes (1) , Rita I. Aroeira (1) , Bryan C. Mounce (2) , Marco Vignuzzi (2) , Henry M. Staines (3) , Miguel Prudêncio (1)

1 ULISBOA - Universidade de Lisboa = University of Lisbon
2 Populations virales et Pathogenèse - Viral Populations and Pathogenesis
3 University of London [London]

Prior to infecting erythrocytes and causing malaria symptoms, Plasmodium parasites undergo an obligatory phase of invasion and extensive replication inside their mammalian host's liver cells that depends on the parasite's ability to obtain the nutrients it requires for its intra-hepatic growth and multiplication. Here, we show that L-arginine (Arg) uptake through the host cell's SLC7A2-encoded transporters is essential for the parasite's development and maturation in the liver. Our data suggest that the Arg that is taken up is primarily metabolized by the arginase pathway to produce the polyamines required for Plasmodium growth. Although the parasite may hijack the host's biosynthesis pathway, it relies mainly upon its own arginase-AdoMetDC/ODC pathway to acquire the polyamines it needs to develop. These results identify for the first time a pivotal role for Arg-dependent polyamine production during Plasmodium's hepatic development and pave the way to the exploitation of strategies to impact liver infection by the malaria parasite through the modulation of Arg uptake and polyamine synthesis.

Keywords: Cellular microbiology; Mechanisms of disease; Parasite biology

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology

Patricia Meireles, Antonio M. Mendes, Rita I. Aroeira, Bryan C. Mounce, Marco Vignuzzi, et al.. Uptake and metabolism of arginine impact Plasmodium development in the liver. Scientific Reports, 2017, 7 (1), pp.4072. ⟨10.1038/s41598-017-04424-y⟩. ⟨pasteur-01570217⟩