Survival of the human malaria parasite Plasmodium falciparum in the circulation of the host relies on its ability to drastically alter its red blood cell (RBC) host cell. This remodelling is mediated by the export of parasite derived proteins which interact with components of the RBC cytoskeleton and modify RBC behaviour. As a consequence of this remodelling the parasite must cytoadhere within the microvasculature of the host to avoid clearance by the spleen. In asexual stage parasites the formation of knob structures underneath the RBC membrane in addition to other exported parasite proteins drives a dramatic change in the RBC deformability. Adherence is mediated by the assembly of a virulence complex comprising the P. falciparum erythrocyte membrane protein-1 (PfEMP1) and the knob-associated histidine-rich protein (KAHRP) at the RBC membrane. Trafficking of these proteins to the RBC membrane occurs through a parasite specific Golgi-like organelle called the Maurer’s cleft.
Using super resolution microscopy and long term fluorescence microscopy we investigate the relationship between host cell cytoskeleton remodelling and the assembly of knobs at the erythrocyte membrane, in particular the relationship between the major knob component the knob associated his-rich protein KAHRP and other exported proteins and structures.
We functionally assess the RBC cytoskeleton remodelling processes across blood stage development, by employing ektocytometry and spleen mimic filtration assays. We show that the host cell remodelling of both the asexual stage parasites and gametocytes is underpinned by changes to the RBC cytoskeleton, these modifications allow for an array of changes facilitating adherence within the microvasculature of the host, replicate and facilitate disease transmission. An understanding of these processes is essential to understanding the central role that parasite adhesion plays in disease and parasite biology.