Linking epigenetics to virulence gene expression in malaria pathogenesis

What is it about?

Epigenetic mechanisms partly regulate the ability of the malaria parasite, Plasmodium falciparum, to cause severe disease. Epigenetic control is mediated by enzymes classified as writers, readers, or erasers. Writers add specific epigenetic marks on genes or genetic structures, while erasers remove these marks. Some studies indicate that var genes, which produce proteins responsible for severe malaria, are positively associated with fever and high blood lactate levels, and the expression of an eraser, Plasmodium sirtuins, correlates positively with var gene expression levels. We aimed to investigate whether heat shock and/or lactate levels can lead to increased expression of Plasmodium sirtuins and var genes that encode proteins linked to severe malaria, using an in vitro model. Fever and elevated blood lactate levels reflect host stress. Our findings show that heat shock, in the form of fever, increases the expression of a Plasmodium sirtuin, PfSir2B, in the trophozoite stage but not in the ring stage of the parasite. Since var gene expression is typically reduced in the trophozoite stage, we assessed their expression only in the ring stage; however, heat shock did not influence their expression. Exposure to high lactate levels did not cause any changes in the expression of the virulence-related var gene or genes encoding Plasmodium sirtuins. While some relationships may not be causal, our results demonstrate that, in laboratory-adapted isolates of P. falciparum, heat shock can induce a modest increase in PfSir2B transcripts in the trophozoite stage. Host factors can impact the course or outcome of malaria.

Featured Image

Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Why is it important?

Our findings contribute to other studies focused on identifying stronger potential biomarkers that predict severe malaria and identifying novel targets for therapeutic intervention, better prevention and treatment strategies of severe malaria.

Perspectives