Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2021

Understanding the molecular basis of Plasmodium parasite protein export; a key to malaria pathogenesis (#68)

Brendan Crabb AC 1 , Mikha Gabriela 1 , Hayley E Bullen 1 , Paul R Gilson 1
  1. Burnet Institute, Melbourne, VIC, Australia

Malaria a devastating disease caused by infection of the blood with Plasmodium parasites, afflicts over 200 million people per year, tragically resulting in nearly half a million deaths. Comprehensive understanding of the biology of the parasite is needed to develop improved drugs and vaccines. Malaria parasites infect, grow and reproduce within human red blood cells (RBCs), encased inside a parasitophorous vacuole.  From there, the parasite then completely modifies the RBC in order to proliferate rapidly and to avoid the human immune system by exporting hundreds of its proteins into the RBC compartment. In order to gain access to the RBC, the exported proteins must traverse the vacuole membrane. A decade ago, we discovered the molecular gateway complex responsible for this task and called it PTEX. Until recently we thought that PTEX acted as a static barcode reader at the vacuole membrane that selectively translocated cargo proteins into the RBC once they reached the vacuole space. In a recent breakthrough, we have instead discovered one of PTEX’s protein subunits called HSP101, may in fact first recognise exported proteins inside the parasite before escorting them to the rest of PTEX for translocation into the RBC. We have also discovered another vacuole protein called P113, that may both assist PTEX to translocate very large, multi-domain exported proteins as well as help maintain the correct architecture of the vacuole membrane around the parasite. These discoveries further our understanding of how PTEX functions both within the parasite and around the outside of the parasite in the vacuole, and could inform future development of small molecule inhibitors to block protein export thereby arresting parasite growth.