Alteration of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum: a pattern emerges

Abstract Background In the malaria parasite Plasmodium falciparum the expression of ‘ var ’ virulence genes is regulated through epigenetic mechanisms. P . falciparum sirtuin epigenetic regulators have a direct effect on their var gene expression patterns, are increased in the 3D7 laboratory strain on exposure to heat shock. A Gambia study showed an association with fever, blood lactate and var genes commonly expressed in severe malaria, and between PfSir2A and group B var . A Kenyan study extended this association to between PfSir2A and overall var transcript level. We investigated a causal link between heat shock or lactate levels and sirtuins or var expression. Methods In vitro experiments were conducted using laboratory and recently-laboratory-adapted Kenyan isolates of P. falciparum to follow up the correlative findings of the field study. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, qPCR was used to measure the expression of sirtuins and var genes after highly synchronous cultured parasites had been exposed to 2h or 6h of heat shock at 40°C or elevated lactate. Results Heat shock was shown to increase the expression of PfSir2B in the trophozoites, whereas exposure to lactate was not. After the ring stages were exposed to heat shock and lactate, there was no alteration in the expression of sirtuins and severe-disease-associated upsA and upsB var genes. The association between high blood lactate and sirtuin/ var gene expression that was previously observed in vivo appears to be coincidental rather than causative. Conclusions This study demonstrates that heat stress in laboratory and recently-laboratory-adapted isolates of P. falciparum results in a small increase in PfSir2B transcripts in the trophozoite stages only. This finding adds to our understanding of how patient factors can influence the outcome of Plasmodium falciparum infections.