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Scientific article
Open access
English

Tetracycline analogue-regulated transgene expression in Plasmodium falciparum blood stages using Toxoplasma gondii transactivators

Publication date2005
Abstract

Genetic manipulation has revolutionized research in the Apicomplexan parasite Plasmodium falciparum, the most important causative agent of malaria. However, to date no techniques have been established that allow modifications that are deleterious to blood-stage growth, such as the disruption of essential genes or the expression of dominant-negative transgenes. The recent establishment of a screen for functional transactivators in the related parasite Toxoplasma gondii prompted us to identify transactivators in T. gondii and to examine their functionality in P. falciparum. Tetracycline-responsive minimal promoters were generated based on the characterized P. falciparum calmodulin promoter and used to assess transactivators in P. falciparum. We demonstrate that artificial tetracycline-regulated transactivators isolated in T. gondii are also functional in P. falciparum. By using the tetracycline analogue anhydrotetracycline, efficient, stage-specific gene regulation was achieved in P. falciparum. This regulatable expression technology has clear potential for the study of essential gene function in P. falciparum blood stages. On the other hand, the identified transactivators are not functional in mammalian cells, consistent with the fundamental differences in the mechanism of gene regulation between Apicomplexan parasites and their human hosts.

Keywords
  • Amino Acid Sequence
  • Animals
  • Erythrocytes/parasitology
  • Gene Expression Regulation/drug effects
  • Molecular Sequence Data
  • Plasmodium falciparum/genetics
  • Tetracyclines/pharmacology
  • Toxoplasma/genetics
  • Trans-Activators/physiology
  • Transgenes
Citation (ISO format)
MEISSNER, Markus et al. Tetracycline analogue-regulated transgene expression in Plasmodium falciparum blood stages using Toxoplasma gondii transactivators. In: Proceedings of the National Academy of Sciences of the United States of America, 2005, vol. 102, n° 8, p. 2980–2985. doi: 10.1073/pnas.0500112102
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Article (Accepted version)
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Identifiers
ISSN of the journal0027-8424
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