Gene encoding a deubiquitinating enzyme is mutated in artesunate- and chloroquine-resistant rodent malaria parasites
2007

Mutations in a Gene Linked to Drug Resistance in Malaria Parasites

publication Evidence: moderate

Author Information

Author(s): Hunt Paul, Afonso Ana, Creasey Alison, Culleton Richard, Sidhu Amar Bir Singh, Logan John, Valderramos Stephanie G, McNae Iain, Cheesman Sandra, do Rosario Virgilio, Carter Richard, Fidock David A, Cravo Pedro

Primary Institution: Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh

Hypothesis

What resistance mechanisms are possible and what are their genetic bases?

Conclusion

The study identified two mutations in a gene encoding a deubiquitinating enzyme that may contribute to drug resistance in malaria parasites.

Supporting Evidence

  • Two mutations in the UBP-1 gene were identified in chloroquine-resistant clones.
  • Mutations occurred independently under drug selection with chloroquine or artesunate.
  • Each mutation maps to a critical residue in a homologous human deubiquitinating protein structure.

Takeaway

Scientists found changes in a specific gene that help malaria parasites resist drugs like artemisinin and chloroquine, which are used to treat malaria.

Methodology

The study used genetic crosses and Linkage Group Selection to analyze mutations in malaria parasites under drug selection.

Limitations

The study does not provide direct evidence linking UBP-1 mutations to artemisinin resistance.

Digital Object Identifier (DOI)

10.1111/j.1365-2958.2007.05753.x

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