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Transient silencing of Plasmodium falciparum bifunctional glucose‐6‐phosphate dehydrogenase− 6‐phosphogluconolactonase
Author(s) -
Crooke Almudena,
Diez Amalia,
Mason Philip J,
Bautista José M.
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05174.x
Subject(s) - biology , gene silencing , plasmodium falciparum , gene , transcription (linguistics) , gene expression , microbiology and biotechnology , biochemistry , immunology , malaria , linguistics , philosophy
The bifunctional enzyme glucose‐6‐phosphate dehydrogenase‐6‐phosphogluconolactonase (G6PD‐6PGL) found in Plasmodium falciparum has unique structural and functional characteristics restricted to this genus. This study was designed to examine the effects of RNA‐mediated PfG6PD‐6PGL gene silencing in cultures of P. falciparum on the expression of parasite antioxidant defense genes at the transcription level. The highest degree of G6PD‐6PGL silencing achieved was 86% at the mRNA level, with a recovery to almost normal levels within 24 h, indicating only transient diminished expression of the PfG6PD‐6PGL gene. PfG6PD‐6PGL silencing caused arrest of the trophozoite stage and enhanced gametocyte formation. In addition, an immediate transcriptional response was shown by thioredoxin reductase suggesting that P. falciparum G6PD‐6PGL plays a physiological role in the specific response of the parasite to intracellullar oxidative stress. P. falciparum transfection with an empty DNA vector also promoted intracellular stress, as determined by mRNA up‐regulation of antioxidant genes. Collectively, our findings point to an important role for this enzyme in the parasite's infection cycle. The different characteristics of G6PD‐6PGL with respect to its homologue in the host make it an ideal target for therapeutic strategies.