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Dynamic of plasmodium falciparum chloroquine resistance transporter gene Pfcrt K76T mutation five years after withdrawal of chloroquine in Burkina Faso.

ABSTRACT: We investigated the evolution of Pfcrt K76T mutation five years after the withdrawal of chloroquine in Burkina Faso. A total of 675 clinical isolates collected from October 2010 to September 2012 were successfully genotyped. Single nucleotide polymorphism in Pfcrt (codon 76) gene was analyzed. The prevalence of resistant Pfcrt 76T allele was 20.55%. There was a progressive decrease of the proportion of mutant type pfcrt T76 from 2010 to 2012 (X2=5.508 p=0.0189). Our results suggest a progressive return of the wild type Pfcrt K76 in Burkina Faso but the prevalence of the mutants Pfcrt T76 still remains high.

SUBMITTER: Sondo P

PROVIDER: S-EPMC4606025 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Dynamic of plasmodium falciparum chloroquine resistance transporter gene Pfcrt K76T mutation five years after withdrawal of chloroquine in Burkina Faso.

Sondo Paul P Derra Karim K Tarnagda Zekiba Z Nakanabo Seydou Diallo SD Zampa Odile O Kazienga Adama A Valea Innocent I Sorgho Hermann H Ouedraogo Jean-Bosco JB Guiguemde Tinga Robert TR Tinto Halidou H

The Pan African medical journal 20150609

We investigated the evolution of Pfcrt K76T mutation five years after the withdrawal of chloroquine in Burkina Faso. A total of 675 clinical isolates collected from October 2010 to September 2012 were successfully genotyped. Single nucleotide polymorphism in Pfcrt (codon 76) gene was analyzed. The prevalence of resistant Pfcrt 76T allele was 20.55%. There was a progressive decrease of the proportion of mutant type pfcrt T76 from 2010 to 2012 (X2=5.508 p=0.0189). Our results suggest a progressive ...[more]

PMID: 26516402

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Iron is a substrate of the <i>Plasmodium falciparum</i> chloroquine resistance transporter PfCRT in <i>Xenopus</i> oocytes.

Project description:The chloroquine resistance transporter of the human malaria parasite Plasmodium falciparum, PfCRT, is an important determinant of resistance to several quinoline and quinoline-like antimalarial drugs. PfCRT also plays an essential role in the physiology of the parasite during development inside erythrocytes. However, the function of this transporter besides its role in drug resistance is still unclear. Using electrophysiological and flux experiments conducted on PfCRT-expressing Xenopus laevis oocytes, we show here that both wild-type PfCRT and a PfCRT variant associated with chloroquine resistance transport both ferrous and ferric iron, albeit with different kinetics. In particular, we found that the ability to transport ferrous iron is reduced by the specific polymorphisms acquired by the PfCRT variant as a result of chloroquine selection. We further show that iron and chloroquine transport via PfCRT is electrogenic. If these findings in the Xenopus model extend to P. falciparum in vivo, our data suggest that PfCRT might play a role in iron homeostasis, which is essential for the parasite's development in erythrocytes.

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