Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

Peter Ellekvist, Jorge Maciel, Godfree Mlambo, Christina H. Ricke, Hanne Colding, Dan A. Klaerke, Nirbhay Kumar

Research output: Contribution to journalArticle

Abstract

Regulated K+ transport across the plasma membrane is of vital importance for the survival of most cells. Two K+ channels have been identified in the Plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission through the mosquito vector remains unknown. We hypothesize that these two K+ channels mediate the transport of K+ in the parasites, and thus are important for parasite survival. To test this hypothesis, we identified the orthologue of one of the P. falciparum K + channels, PfKch1, in the rodent malaria parasite P. berghei (PbKch1) and examined the biological role by performing a targeted disruption of the gene encoding PbKch1. The deduced amino acid sequence of the six transmembrane domains of PfKch1 and PbKch1 share 82% identity, and in particular the pore regions are completely identical. The PbKch1-null parasites were viable despite a marked reduction in the uptake of the K+ congener 86Rb+, and mice infected with PbKch1-null parasites survived slightly longer than mice infected with WT parasites. However, the most striking feature of the phenotype was the virtually complete inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K+ in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut. K+ channels therefore may constitute a potential antimalarial drug target.

Original languageEnglish (US)
Pages (from-to)6398-6402
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number17
DOIs
Publication statusPublished - Apr 29 2008

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Keywords

  • Drug target
  • Malaria
  • Mosquito
  • Pathogenesis

ASJC Scopus subject areas

  • Genetics
  • General

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