Research, Malaria Elimination

Fluorescent Parasites for Studying a Key Process in Malaria Transmission

An ISGlobal team develops an assay that will help assess the effect of drugs and other factors on sexual conversion by 'Plasmodium falciparum'

11.10.2019
Fluorescence microscopy of the sexual stages of the new malaria parasite reporter line showing red fluorescence under the control of gexp02 promoter
Photo: H. Portugaliza. Fluorescence microscopy of the sexual stages of the new malaria parasite reporter line

A study led by ISGlobal, an institution supported by “la Caixa”, describes an innovative assay to measure the malaria parasite’s sexual conversion rate, or in other words, the percentage of parasites that abandon the asexual cycle and differentiate into the sexual stage, transmissible to the mosquito. This assay will allow to better characterise the process in the laboratory, and to evaluate the effect of external factors, including drugs, on such process. 

Spreading of malaria between humans is mediated by Anopheles mosquitoes. In order to pass from human blood to the mosquito, the parasite needs to convert from the asexual to the sexual stage, called the gametocyte. Thus, the parasite must reach a balance between multiplying asexually within the same host and generating small percentage of gametocytes to ensure its transmission. This percentage is the sexual conversion rate.  

Given that gametocytes are a priority target for stopping malaria transmission, the team led by Alfred Cortés, ICREA researcher at ISGlobal, has spent the last years studying the factors that regulate the parasite’s sexual conversion. To facilitate this task, they decided to create a transgenic line of parasites that become fluorescent when they initiate sexual conversion. To do so, they introduced the gene for a fluorescent protein – obtained from a sea coral - associated with the regulatory sequence of a gene (gexp02) that is specifically expressed by the sexual stages of the parasite.  

Using these parasites, the research team developed an assay that allows determining the sexual conversion rate in the laboratory in a much simpler, faster and reliable way than the currently used methods. “This assay will help us assess the impact of external factors, including drugs, on the parasite’s conversion rate,” explains Harvie Portugaliza, first author of the study. The results, published in Scientific Reports, also confirm that the gexpo2 gene is specifically expressed by sexual parasites, even the early sexual forms, and therefore “could be used as a marker to detect sexual parasites in epidemiological studies,” adds Cortés.  

Reference

Portugaliza HP, Llorà-Batlle O, Rosanas-Urgell A, Cortés A. Reporter lines base don the gexp02 promoter enable early quantification of sexual conversión rates in the malaria parasite Plasmodium falciparum. Scientific Reports. 2019. 9:14595. https://doi.org/10.1038/s41598-019-50768-y