Inducing sexual conversion in Plasmodium falciparum.

2017 edition

Oriol Llorà

Plasmodium falciparum is transmitted to human hosts through the bites of infected female Anopheles mosquitoes. Inside the host it begins a chronic cycle of asexual growth within erythrocytes. During each asexual cycle, some parasites differentiate into male or female gamete precursors called gametocytes, capable of infecting a new mosquito and undergo sexual reproduction.

The study of gametocytes remains challenging, mainly due to the low levels in peripheral blood and the low rates of sexual conversion under in vitro conditions.  To overcome this problem, we aim to develop a new tool for the study of gametocytes: a conditional over-expression system for pfap2-g – the master regulator of sexual conversion. Our strategy consists in integrating a transgene upstream of the pfap2-g locus that can be deleted with the inducible DiCre recombinase leaving pfap2-g under the control of a constitutive promoter.

In preliminary experiments, we are optimizing the system with an episomally expressed DiCre. Upon activation of DiCre around half of the parasites convert to sexual stages. Our next steps will be to induce gametocyte production in a genetically-competent but non-producing strain and to integrate the DiCre cassette in the genome, which will help to achieve higher sexual conversion rates that may approach 100%.