| Popis: |
Background: In the malaria parasite Plasmodium falciparum the expression of ‘var’ virulence genes is regulated through epigenetic mechanisms. Its sirtuin epigenetic regulators have a direct effect on var gene expression patterns, are increased in a laboratory strain of P. falciparum exposed to heat shock and are positively associated with fever. A Gambia study extended this association to 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. These observations suggest a mechanism through which stress phenotypes in the human host might be sensed via a parasite sirtuin, and virulence gene expression modulated accordingly. 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 influence the expression of PfSir2B in the trophozoites, whereas exposure to lactate was not. After the ring stages were exposed to heat shock, sirtuins, severe-disease-associated upsA and upsB var genes and var genes in general were not altered. More biological replicate experiments will be needed to confirm our observations.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. We could not establish if heat shock can cause an increased expression of sirtuins or var genes in the ring stages. By contrast, the association between hyperlactataemia and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative. |
