Fitness Trade-Offs in the Evolution of Dihydrofolate Reductase and Drug Resistance in Plasmodium falciparum
2011

Evolution of Drug Resistance in Malaria

publication Evidence: moderate

Author Information

Author(s): Costanzo Marna S., Brown Kyle M., Hartl Daniel L.

Primary Institution: Department of Organismic and Evolutionary Biology, Harvard University

Hypothesis

How does the evolution of drug resistance in Plasmodium falciparum occur, particularly in relation to chlorcycloguanil?

Conclusion

The study reveals that the evolutionary pathways to drug resistance in Plasmodium falciparum are complex and influenced by the specific drug used.

Supporting Evidence

  • The study identified multiple evolutionary pathways leading to drug resistance in Plasmodium falciparum.
  • Different mutations in the dihydrofolate reductase gene were shown to confer varying levels of resistance to chlorcycloguanil.
  • Findings suggest that the adaptive landscapes for different antifolate drugs are unique.

Takeaway

This study looks at how malaria parasites become resistant to drugs, showing that different drugs can lead to different paths of resistance.

Methodology

The researchers used a transgenic yeast expression system to study the evolutionary trajectories of drug resistance mutations in the dihydrofolate reductase gene.

Limitations

The study's findings may not directly apply to natural populations of Plasmodium falciparum due to the differences between in vitro and in vivo systems.

Digital Object Identifier (DOI)

10.1371/journal.pone.0019636

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