Luciferase-Expressing Plasmodium falciparum
The effort to eliminate malaria requires the discovery of novel drugs targeting Plasmodium falciparum gametocytes (sexual stage), which are solely responsible for transmission of the parasite by Anopheles mosquitoes to humans. Compared to the asexual stages of the parasite, gametocytes have different susceptibilities to drugs, with the mature stage being the least sensitive.1
Two transgenic P. falciparum cell lines, now available from BEI Resources, support the investigation of late-stage gametocyte physiology using cell-based methods and will help provide a more accurate comparison of different compound activities on the pathogenic asexual stages and the immature and mature gametocytes.
P. falciparum, strain NF54-cg6-ULG8-CBG99 (BEI Resources MRA-1324) is a transgenic line containing a luciferase reporter with enhanced sensitivity, CBG99, driven by ULG8, a promoter highly upregulated in mature gametocytes. MRA-1324 provides a method to quantitatively investigate how compounds targeting key pathways of the parasite redox metabolism affect gametocyte development.2
P.falciparum, strain NF54-cg6-hsp86-PpyRE13 (BEI Resources MRA-1325) is another transgenic line, where the expression of the PpyRE13 luciferase gene is driven by the constitutive hsp86 promoter, resulting in all parasite stages expressing the bioluminescent enzyme.1 MRA-1325 is suitable for the measurement of parasite viability in both gametocytes and asexual stages of the organism, as well as for use in drug screen assays.
Reference:
1. Siciliano, G., et al. “The Nitrobenzoxadiazole Derivative NBDHEX Behaves as Plasmodium falciparum Gametocyte Selective Inhibitor with Malaria Parasite Transmission Blocking Activity.” Pharmaceuticals (Basel) 15 (2022): 168. PubMed: 35215282.
2. Siciliano, G., et al. “A High Susceptibility to Redox Imbalance of the Transmissible Stages of Plasmodium falciparum Revealed with a Luciferase-Based Mature Gametocyte Assay.” Mol. Microbiol. 104 (2017): 306-318. PubMed: 28118506.
MRA-1324 Plasmodium falciparum, Strain NF54-cg6-ULG8-CBG99
MRA-1325 Plasmodium falciparum, Strain NF54-cg6-hsp86-PpyRE13
Image Alt Text: Giemsa-stained P. falciparum parasites (BEI Resources MRA-1324) visualized under a light microscope. (BEI Resources)
Image Credit: Giemsa-stained P. falciparum parasites (MRA-1324) visualized under a light microscope. (BEI Resources)
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