Malaria Pulls a FASt One
| Autor: | Sean T. Prigge, Maroya D. Spalding |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Plasmodium falciparum Drug target Microbiology Article Antimalarials chemistry.chemical_compound Immunology and Microbiology(all) Virology parasitic diseases medicine Animals Molecular Biology Liver stage biology biology.organism_classification medicine.disease Triclosan Fatty acid synthetase complex chemistry Parasitology Fatty Acid Synthases Malaria |
| Zdroj: | Cell Host & Microbe. 4:509-511 |
| ISSN: | 1931-3128 |
| Popis: | Fatty acid biosynthesis has been viewed as an important biological function of and therapeutic target for Plasmodium falciparum asexual blood stage infection. This apicoplast-resident type II pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of the bacterial FabI inhibitor triclosan. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood stage growth. In contrast, mosquito-derived fabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver stage development in vitro. This is characterized by an inability to form intra-hepatic merosomes that normally initiate blood stage infections. These data illuminate key differences between liver and blood stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions. |
| Databáze: | OpenAIRE |
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