Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections
| Autor: | Viswanathan Arun Nagaraj, Manjunatha Chandana Shetty, Vinayagam Sathishkumar, Rajeev R Pandey, Govindarajan Padmanaban, Susanta K. Ghosh, Dhanunjay Mukhi, Pradeep Annamalai Subramani |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Asparaginase
Plasmodium berghei Asparagine synthetase General Physics and Astronomy Fluorescent Antibody Technique Biology Plasmodium Biochemistry General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Gene Knockout Techniques Mice Anopheles parasitic diseases Gametocyte Animals Asparagine Centre for Infectious Disease Research Amino acid synthesis chemistry.chemical_classification Life Cycle Stages Multidisciplinary Organisms Genetically Modified Reverse Transcriptase Polymerase Chain Reaction Aspartate-Ammonia Ligase General Chemistry biology.organism_classification Virology Malaria Centre for Infectious Disease Research and Biosafety Laboratories chemistry Liver |
| Zdroj: | Nature Communications |
| ISSN: | 2381-3652 |
| Popis: | 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. Malaria parasites obtain amino acids primarily from the host, but possess a gene encoding a putative asparagine synthetase. Here, the authors show that this enzyme is functional and that asparagine is crucial for the development of the parasite's sexual stages in mosquitoes and liver stages in mice. |
| Databáze: | OpenAIRE |
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