Uptake and metabolism of arginine impact Plasmodium development in the liver

Abstract 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 gro...

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Autores principales:	Patrícia Meireles, António M. Mendes, Rita I. Aroeira, Bryan C. Mounce, Marco Vignuzzi, Henry M. Staines, Miguel Prudêncio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/133a76af5fe44d84be8a4c8babb2c5dd
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spelling	oai:doaj.org-article:133a76af5fe44d84be8a4c8babb2c5dd2021-12-02T12:32:12ZUptake and metabolism of arginine impact Plasmodium development in the liver10.1038/s41598-017-04424-y2045-2322https://doaj.org/article/133a76af5fe44d84be8a4c8babb2c5dd2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04424-yhttps://doaj.org/toc/2045-2322Abstract 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.Patrícia MeirelesAntónio M. MendesRita I. AroeiraBryan C. MounceMarco VignuzziHenry M. StainesMiguel PrudêncioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrícia Meireles António M. Mendes Rita I. Aroeira Bryan C. Mounce Marco Vignuzzi Henry M. Staines Miguel Prudêncio Uptake and metabolism of arginine impact Plasmodium development in the liver
description	Abstract 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.
format	article
author	Patrícia Meireles António M. Mendes Rita I. Aroeira Bryan C. Mounce Marco Vignuzzi Henry M. Staines Miguel Prudêncio
author_facet	Patrícia Meireles António M. Mendes Rita I. Aroeira Bryan C. Mounce Marco Vignuzzi Henry M. Staines Miguel Prudêncio
author_sort	Patrícia Meireles
title	Uptake and metabolism of arginine impact Plasmodium development in the liver
title_short	Uptake and metabolism of arginine impact Plasmodium development in the liver
title_full	Uptake and metabolism of arginine impact Plasmodium development in the liver
title_fullStr	Uptake and metabolism of arginine impact Plasmodium development in the liver
title_full_unstemmed	Uptake and metabolism of arginine impact Plasmodium development in the liver
title_sort	uptake and metabolism of arginine impact plasmodium development in the liver
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/133a76af5fe44d84be8a4c8babb2c5dd
work_keys_str_mv	AT patriciameireles uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver AT antoniommendes uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver AT ritaiaroeira uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver AT bryancmounce uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver AT marcovignuzzi uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver AT henrymstaines uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver AT miguelprudencio uptakeandmetabolismofarginineimpactplasmodiumdevelopmentintheliver
_version_	1718394141257236480

Uptake and metabolism of arginine impact Plasmodium development in the liver

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