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New Tools to Study Inducible Sexual Conversion in P. falciparum
The differentiation of a small proportion of asexual blood-stage malaria parasites into sexual forms called gametocytes is a pre-requisite for malaria transmission.1,2 A better understanding of this process, called gametocytogenesis, is critical for developing transmission-blocking drugs and vaccines.
Five transgenic Plasmodium falciparum lines have been developed to o study gametocyte biology and triggers for gametocytogenesis. The first four parasite lines (MRA-1303, MRA-1304, MRA-1305, and MRA-1306) possess genome-integrated cassettes in which the TdTomato fluorescent reporter is expressed under the control of the promoter of gexp02, a gametocyte-specific gene and etramp10.3, which encodes an early transcribed membrane protein located at the parasite-host cell interface.1,2,3,4 The fifth transgenic line (MRA-1308) harbors the inducible Cre recombinase (DiCre) expression cassette that is integrated at the lisp1 locus and can be used for inducible sexual conversion, achieving sexual conversion rates of up to 90%.5
Researchers can use these lines for accurate and efficient quantification of sexual conversion rates under different conditions. These lines can also be used to obtain pure populations of sexually committed parasites for genomic, transcriptomic, proteomic and metabolomic characterization, and high-throughput screening of compounds targeting gametocytes.
These parasite lines are now available worldwide to investigators and institutions registered with BEI Resources under the following item numbers:
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BEI Resources
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Novel Transgenic P. falciparum Lines
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| MRA-1303 |
Plasmodium falciparum, Strain NF54-gexp02-Tom |
| MRA-1304 |
Plasmodium falciparum, Strain 3D7-B E5-gexp02-Tom |
| MRA-1305 |
Plasmodium falciparum, Strain NF54-10.3-Tom |
| MRA-1306 |
Plasmodium falciparum, Strain 3D7-B E5-10.3-Tom |
| MRA-1308 |
Plasmodium falciparum, Strain 3D7-A 1.2Bind |
References:
1. Portugaliza, H. P., et al. “Reporter Lines Based on the gexp02 Promoter Enable Early Quantification of Sexual Conversion Rates in the Malaria Parasite Plasmodium falciparum.” Sci. Rep. 9 (2019): 14595. PubMed: 31601834.
2. Kafsack, B. F. C., et al. “A Transcriptional Switch Underlies Commitment to Sexual Development in Malaria Parasites.” Nature 507 (2014): 248-52. PubMed: 24572369.
3. Spielmann, T., D. J. P. Fergusen and H.-P. Beck.. “etramps, a New Plasmodium falciparum Gene Family Coding for Developmentally Regulated and Highly Charged Membrane Proteins Located at The Parasite-Host Cell Interface.” Mol. Biol. Cell 14 (2003): 1529-44. PubMed: 12686607.
4. Buchholz, K., et al. “A High-Throughput Screen Targeting Malaria Transmission Stages Opens New Avenues for Drug Development.” J Infect Dis. 203 (2011):1445-53. PubMed: 21502082.
5. Llorà-Batlle, O., et al. “Conditional Expression of Pfap2-G For Controlled Massive Sexual Conversion in Plasmodium falciparum.” Sci Adv. 6 (2020): eaaz5057. PubMed: 32577509.
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