Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes

Andrea Ecker, Viswanathan Lakshmanan, Photini Sinnis, Isabelle Coppens, David A. Fidock

Research output: Contribution to journalArticle

Abstract

Resistance of the human malarial parasite Plasmodium falciparum to the antimalarial drug chloroquine has rapidly spread from several independent origins and is now widely prevalent throughout the majority of malaria-endemic areas. Field studies have suggested that chloroquine-resistant strains might be more infective to mosquito vectors. To test the hypothesis that the primary chloroquine resistance determinant, mutations in PfCRT, facilitates parasite transmission under drug pressure, we have introduced a mutant or wild-type pfcrt allele into the rodent model malarial parasite Plasmodium berghei. Our results show that mutant PfCRT from the chloroquine-resistant 7G8 strain has no effect on asexual blood stage chloroquine susceptibility in vivo or ex vivo but confers a significant selective advantage in competitive mosquito infections in the presence of this drug, by protecting immature gametocytes from its lethal action. Enhanced infectivity to mosquitoes may have been a key factor driving the worldwide spread of mutant pfcrt.

Original languageEnglish (US)
Pages (from-to)228-236
Number of pages9
JournalJournal of Infectious Diseases
Volume203
Issue number2
DOIs
StatePublished - Jan 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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