The mutually exclusive expression of var genes in blood-stage P. falciparum parasites is a major virulence factor in falciparum malaria. This depends partly upon sirtuin deacetylase enzymes - as has been shown by mutagenesis studies disrupting the sirtuin genes in cultured parasites. Furthermore, a field study of direct patient isolates previously showed that high expression of sirtuins correlates with high expression of severe-disease-associated var genes, and this, in turn, correlates with stress factors in the human host: high fever and hyperlactatemia. Our present work seeks to determine cause-and-effect in this relationship: can host stress factors actually cause increased sirtuin expression &hypen; and hence potential changes in virulence gene expression? To investigate this, cultured parasites were exposed to heatshock and/or lactate, and sirtuin expression was assessed by RTPCR. We previously showed that in the laboratory line 3D7, heatshock, but not lactate alone, can lead to increased expression of sirtuin RNA. We have now extended this work to several recently-lab-adapted field strains, to establish the generality of the phenomenon, and have begun to investigate the associated var gene expression profiles. This work ultimately aims to improve our understanding of how P. falciparum can respond to variable conditions in its human host.
