Targeted disruption of Plasmodium falciparum cysteine protease, falcipain 1, reduces oocyst production, not erythrocytic stage growth

Autor: Beata Czesny, Saliha Eksi, Matthew Bogyo, Kim C. Williamson, Doron C. Greenbaum
Rok vydání: 2004
Předmět:
Zdroj: Molecular Microbiology. 53:243-250
ISSN: 1365-2958
0950-382X
DOI: 10.1111/j.1365-2958.2004.04108.x
Popis: Summary Cysteine proteases are currently targets for drug development in a number of parasitic diseases, including malaria. In Plasmodium falciparum , the parasite responsible for the most virulent form of human malaria, there are four members of the cathepsin L-like family of cysteine proteases. Three of these (falcipains 2A, 2B and 3) are thought to be primarily involved in haemoglobin digestion, whereas falcipain 1 has recently been linked to erythrocyte invasion. Neither their expression nor their role in P. falciparum gametocytogenesis, which is required for malaria transmission, has been eval- uated. In this study, RNA transcripts for the falcipain family members were identified as the parasite developed through all five stages of gametocytogen- esis. Falcipain 1 transcript was upregulated in gametocytes, while levels of falcipain 2A/2B decreased in late-stage gametocytes and gametes. To evaluate the function of falcipain 1, the gene was disrupted, and clones from independent transforma- tions were isolated. The asexual growth of the falci- pain 1 minus clones was not overtly affected, and they produced morphologically normal gametocytes and gametes. However, when falcipain 1 minus para- sites were fed to a mosquito, oocyst production was reduced by 70-90%, suggesting an important role for falcipain 1 during parasite development in the mosquito midgut.
Databáze: OpenAIRE
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