Genetic variants associated with heat shock sensitivity in Plasmodium falciparum 3D7-A parasites

Periodic fever is the most characteristic clinical feature of human malaria. However, how parasites survive malarial febrile episodes, which often involve temperatures above 40 degrees, is not known. To understand the molecular basis of heat shock (HS) resistance in Plasmodium falciparum, we took advantage of previously developed P. falciparum lines adapted to periodic HS (3D7-A-HS) and their non-selected controls maintained in parallel (3D7-A). Their ability to adapt in only a few cycles suggested that the parental parasite population contained a selectable subset of parasites resistant to HS. Whole genome sequencing of both 3D7-A-HS and 3D7-A revealed a single nucleotide polymorphism (SNP) that in two independent selection experiments was predominant in 3D7-A control lines, but almost absent in the 3D7-A-HS selected lines. This result led to the identification of a new pathway of HS resistance, involving a transcription factor that drives a protective response under heat stress conditions.