This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: The malaria parasite is able to detect changes in its host's environment and respond by increasing the production of sexual forms capable of being transmitted to mosquitoes. A study led by the Barcelona Institute for Global Health (ISGlobal) identifies the molecular mechanism underlying this process.
The findings, published in Nature Microbiology, answer what has been one of the major unanswered questions in malaria research for decades. During infection in human blood, the malaria parasite Plasmodium falciparum faces two competing demands: On the one hand, it must multiply to sustain the infection; on the other, some parasites must develop into sexual forms known as gametocytes to be transmitted to other people through mosquitoes. Whether to continue multiplying or become gametocytes is the key decision in the life cycle of P. falciparum, the parasite responsible for most severe cases of malaria.
It has long been known that the parasite can detect changes in its host's environment, such as fever or shortages of specific nutrients, and adjust its production of gametocytes accordingly: When conditions become unfavorable, it is advantageous for the parasite to invest more resources in transmission to a mosquito to infect another human host. In recent years, researchers have identified regulators such as gdv1 and ap2-g, which play a central role in initiating the formation of gametocytes. It was also known that stressful conditions for the parasite, such as nutrient limitation, promote gametocyte production, but the molecular mechanism triggering this response remained unknown.
To uncover it, the research team combined genomics, epigenomics, transcriptomics, proteomics and genetic engineering. Parasites were exposed separately to three stress conditions: nutrient limitation, treatment with the antimalarial drug DHA, and a simulated fever episode. The researchers then analyzed which genes were activated, which proteins increased in abundance, and how the organization of chromatin—the structure that regulates access to DNA—changed.
The same experiments were also carried out in parasites in which the regulators involved in the process had been genetically modified. "All three stimuli activated the same regulatory pathway. They all triggered similar changes in the gdv1 and ap2-g genes," explains Elisabet Tintó, ISGlobal researcher and first author of the study.
The study shows that the stress response does not simply involve switching genes on, but also reorganizing heterochromatin, a form of DNA packaging that keeps certain genes silenced. The system also includes its own built-in control mechanism. Once activated, GDV1 triggers conversion into gametocytes while simultaneously inducing the production of gdv1-as, an RNA molecule that represses gdv1 activity.
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