Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity

Li Min Ting, Mathieu Gissot, Alida Coppi, Photini Sinnis, Kami Kim

Research output: Contribution to journalArticle

Abstract

Malaria continues to devastate sub-Saharan Africa owing to the emergence of drug resistance to established antimalarials and to the lack of an efficacious vaccine. Plasmodium species have a unique streamlined purine pathway in which the dual specificity enzyme purine nucleoside phosphorylase (PNP) functions in both purine recycling and purine salvage. To evaluate the importance of PNP in an in vivo model of malaria, we disrupted PyPNP, the gene encoding PNP in the lethal Plasmodium yoelii YM strain. P. yoelii parasites lacking PNP were attenuated and cleared in mice. Although able to form gametocytes, PNP-deficient parasites did not form oocysts in mosquito midguts and were not transmitted from mosquitoes to mice. Mice given PNP-deficient parasites were immune to subsequent challenge to a lethal inoculum of P. yoelii YM and to challenge from P. yoelii 17XNL, another strain. These in vivo studies with PNP-deficient parasites support purine salvage as a target for antimalarials. They also suggest a strategy for the development of attenuated nontransmissible metabolic mutants as blood-stage malaria vaccine strains.

Original languageEnglish (US)
Pages (from-to)954-958
Number of pages5
JournalNature Medicine
Volume14
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Fingerprint

Plasmodium yoelii
Purine-Nucleoside Phosphorylase
Immunity
Parasites
Salvaging
Antimalarials
Culicidae
Malaria
Malaria Vaccines
Gene encoding
Plasmodium
Oocysts
Africa South of the Sahara
Recycling
Drug Resistance
Blood
Vaccines
purine
Enzymes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity. / Ting, Li Min; Gissot, Mathieu; Coppi, Alida; Sinnis, Photini; Kim, Kami.

In: Nature Medicine, Vol. 14, No. 9, 09.2008, p. 954-958.

Research output: Contribution to journalArticle

Ting, Li Min ; Gissot, Mathieu ; Coppi, Alida ; Sinnis, Photini ; Kim, Kami. / Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity. In: Nature Medicine. 2008 ; Vol. 14, No. 9. pp. 954-958.
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