The causative agent of malaria, Plasmodium spp, resides in enucleated erythrocytes, devoid of trafficking machinery. In order to survive inside this host the parasite must import nutrients, and evade the immune system. These processes require proteins to be exported out of the parasite, crossing the plasma membrane (PM) and the parasitophorous vacuole space (PV) and membrane (PVM), into the host cytoplasm and on to where the proteins are required. A protein translocon that facilitates transport across the PVM has been identified, termed PTEX, which consists of 5 major protein components, including the AAA+ ATPase HSP101 predicted to provide the energy for protein translocation1 . Protein members of this class often interact transiently with other chaperone components, including HSP70/HSP40 systems.
We have shown that parasite derived HSP70x has potential to interact with exported proteins in the PV and within the erythrocyte, such as the importance virulence protein PfEMP12 . We probe potential parasite derived interacting partners, using localization and biochemical techniques. We have used multiple methods to knockout the gene, and to knock down the level of protein expression in an inducible manner. We will discuss the phenotype of parasites lacking this chaperone, and its implications in export and pathogenicity of P. falciparum.
These data will help elucidate the working mechanism of protein export in the parasite and provide new and exciting opportunities for drug development.