Poster Presentation First Malaria World Congress 2018

Conserved and divergent mechanisms of merozoite invasion into the human erythrocyte: insights from the non-Laverania malaria parasites (#237)

Oliver Lyth 1 , Katherine Wright 1 , Ellen Knuepfer 2 , Isabelle Henshall 3 , Gema Vizcay 4 , Anthony Holder 2 , Lawrence Bannister 4 , Danny Wilson 3 , Jake Baum 1
  1. Imperial College London, South Kensington, London, UK, United Kingdom
  2. Francis Crick Institute, London
  3. University of Adelaide, Adelaide, SA, Australia
  4. Kings College London, London, UK

Invasion of erythrocytes by the Plasmodium blood-stage merozoite is key to the progression of malaria disease yet we still do not fully understand the mechanics of entry and the role key receptor-ligand interactions play in the process. Fundamentally, efforts to date have focused on key molecular differences across Plasmodium species, or between strains, defining alternative routes of invasion into the same host cell. Yet many processes are likely conserved. Towards defining the fundamental mechanics of pan-Plasmodium merozoite invasion processes, we have developed a new work flow for isolating and imaging the free merozoite of Plasmodium knowlesi, a zoonotic malaria phylogenetically closely related to P. vivax - itself the second main cause of global malaria morbidity. With access to invasive knowlesi and falciparum merozoites and the potential to study each side-by-side into the same human cells, we are beginning to address each of the core conserved machineries that likely underpin the same fundamental process of red cell entry across Plasmodium species. Here I will present our latest work exploring the dynamics of the merozoite-erythrocyte tight junction during entry, the Basigin (CD147) erythrocyte surface receptor, ligands identified for Basigin’s use by P. falciparum (the RH5 complex) and whether a similar complex also exists in the non-Laverania subgenera of Plasmodium species.