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

Fingerprint

Plasmodium
Chloroquine
Culicidae
Parasites
Plasmodium berghei
Antimalarials
Plasmodium falciparum
Pharmaceutical Preparations
Malaria
Rodentia
Alleles
Pressure
Mutation
Infection

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes. / Ecker, Andrea; Lakshmanan, Viswanathan; Sinnis, Photini; Coppens, Isabelle; Fidock, David A.

In: Journal of Infectious Diseases, Vol. 203, No. 2, 15.01.2011, p. 228-236.

Research output: Contribution to journalArticle

@article{e32acce85e444439a716948b741078c5,
title = "Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes",
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.",
author = "Andrea Ecker and Viswanathan Lakshmanan and Photini Sinnis and Isabelle Coppens and Fidock, {David A.}",
year = "2011",
month = "1",
day = "15",
doi = "10.1093/infdis/jiq036",
language = "English (US)",
volume = "203",
pages = "228--236",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes

AU - Ecker, Andrea

AU - Lakshmanan, Viswanathan

AU - Sinnis, Photini

AU - Coppens, Isabelle

AU - Fidock, David A.

PY - 2011/1/15

Y1 - 2011/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79851482799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79851482799&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiq036

DO - 10.1093/infdis/jiq036

M3 - Article

C2 - 21288823

AN - SCOPUS:79851482799

VL - 203

SP - 228

EP - 236

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 2

ER -