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Contribution of the pfmdr1 gene to antimalarial drug-resistance

Manoj T Duraisingh1, Alan F Cowman

  • 1Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, USA.

Acta Tropica
|May 7, 2005
PubMed

Insights

The Plasmodium falciparum multidrug resistance protein-1 (pfmdr1) gene is linked to antimalarial drug resistance. Mutations and amplification of pfmdr1 influence resistance to chloroquine, quinine, mefloquine, and artemisinin derivatives.

Area of Science:

  • Malariology
  • Molecular Biology
  • Drug Resistance Research

Background:

  • Drug resistance in Plasmodium falciparum is a significant challenge for malaria control.
  • The Plasmodium falciparum multidrug resistance protein-1 (pfmdr1), also known as P-glycoprotein homolog 1 (Pgh-1), is a key transporter involved in drug efflux.

Purpose of the Study:

  • To investigate the association between pfmdr1 gene mutations/amplification and resistance to various antimalarial drugs.
  • To understand the role of pfmdr1 in modulating resistance levels to different drug classes.

Main Methods:

  • Analysis of pfmdr1 gene mutations and amplification in laboratory and field isolates of Plasmodium falciparum.
  • Correlation studies between genetic variations in pfmdr1 and observed drug resistance phenotypes.

Main Results:

  • Mutations in the pfmdr1 gene are associated with chloroquine resistance, though not essential.
  • pfmdr1 plays a role in modulating resistance to chloroquine and quinine.
  • Wildtype pfmdr1 and gene amplification correlate with resistance to mefloquine and artemisinin derivatives, indicating multidrug resistance.

Conclusions:

  • pfmdr1 is a critical factor in the development of resistance to multiple antimalarial drugs.
  • Understanding pfmdr1 polymorphism and amplification is crucial for predicting and managing antimalarial drug resistance globally.

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