Authors

L Anagu ¹; C Merrick¹;  ¹ Keele University

Discussion

Sirtuin deacetylase enzymes are major players in the mutually exclusive expression of var genes in blood-stage P. falciparum parasites. This has been shown by mutagenesis studies in cultured parasites, and a field study of direct patient isolates has also shown that high expression of sirtuins correlates with high expression of severe-disease-associated var genes. Furthermore, this in turn correlates with stress factors in the human host: high fever and hyperlactatemia. In this work we seek to determine cause-and-effect in this relationship: can host stress factors actually cause increased sirtuin expression – and hence potential changes in virulence gene expression?  Cultured parasites were exposed to heatshock and/or lactate, and sirtuin expression was assessed by RTPCR. In a second line of experiment, a luciferase reporter gene under a sirtuin promoter was generated and characterised, providing independent protein-level readout.  We show that heatshock and prolonged exposure of schizonts to lactate can lead to increased expression of sirtuin RNA, and we discuss potential disparities between the RNA and protein readouts.  This work will ultimately improve our understanding of how P. falciparum can respond to variable conditions in its human host