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Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections

Nagaraj, Viswanathan A and Mukhi, Dhanunjay and Sathishkumar, Vinayagam and Subramani, Pradeep A and Ghosh, Susanta K and Pandey, Rajeev R and Shetty, Manjunatha C and Padmanaban, Govindarajan (2015) Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections. In: NATURE COMMUNICATIONS, 6 .

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Official URL: http://dx.doi.org/10.1038/ncomms9775

Abstract

The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual-and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Centre for Infectious Disease Research
Depositing User: Id for Latest eprints
Date Deposited: 06 Jan 2016 07:00
Last Modified: 06 Jan 2016 07:00
URI: http://eprints.iisc.ac.in/id/eprint/53052

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