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Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections.
Nagaraj, Viswanathan A; Mukhi, Dhanunjay; Sathishkumar, Vinayagam; Subramani, Pradeep A; Ghosh, Susanta K; Pandey, Rajeev R; Shetty, Manjunatha C; Padmanaban, Govindarajan.
Afiliación
  • Nagaraj VA; Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
  • Mukhi D; Centre for Infectious Disease Research, Indian Institute of Science, Bangalore 560 012, India.
  • Sathishkumar V; Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
  • Subramani PA; Centre for Infectious Disease Research, Indian Institute of Science, Bangalore 560 012, India.
  • Ghosh SK; National Institute of Malaria Research (Field Unit), Nirmal Bhawan, ICMR complex, Poojanahalli, Off NH-7, Kannamangala Post, Bangalore 562 110, India.
  • Pandey RR; National Institute of Malaria Research (Field Unit), Nirmal Bhawan, ICMR complex, Poojanahalli, Off NH-7, Kannamangala Post, Bangalore 562 110, India.
  • Shetty MC; Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
  • Padmanaban G; Centre for Infectious Disease Research, Indian Institute of Science, Bangalore 560 012, India.
Nat Commun ; 6: 8775, 2015 Nov 04.
Article en En | MEDLINE | ID: mdl-26531182
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium berghei / Asparagina / Aspartatoamoníaco Ligasa / Malaria Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium berghei / Asparagina / Aspartatoamoníaco Ligasa / Malaria Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido