Super-resolution dissection of coordinated events during malaria parasite invasion of the human erythrocyte.
Erythrocyte invasion by the merozoite is an obligatory stage in Plasmodium parasite infection and essential to malaria disease progression. Attempts to study this process have been hindered by the poor invasion synchrony of merozoites from the only in vitro culture-adapted human malaria parasite, Plasmodium falciparum. Using fluorescence, three-dimensional structured illumination, and immunoelectron microscopy of filtered merozoites, we analyze cellular and molecular events underlying each discrete step of invasion. Monitoring the dynamics of these events revealed that commitment to the process is mediated through merozoite attachment to the erythrocyte, triggering all subsequent invasion events, which then proceed without obvious checkpoints. Instead, coordination of the invasion process involves formation of the merozoite-erythrocyte tight junction, which acts as a nexus for rhoptry secretion, surface-protein shedding, and actomyosin motor activation. The ability to break down each molecular step allows us to propose a comprehensive model for the molecular basis of parasite invasion.
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia.
David T
DT
Riglar
Dave
D
Richard
Danny W
DW
Wilson
Michelle J
MJ
Boyle
Chaitali
C
Dekiwadia
Lynne
L
Turnbull
Fiona
F
Angrisano
Danushka S
DS
Marapana
Kelly L
KL
Rogers
Cynthia B
CB
Whitchurch
James G
JG
Beeson
Alan F
AF
Cowman
Stuart A
SA
Ralph
Jake
J
Baum
D002448:Cell Adhesion; D004912:Erythrocytes / Q000469:parasitology* / Q000648:ultrastructure*; D006801:Humans; D021621:Imaging, Three-Dimensional; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000473:pathology*; D052940:Merozoites / Q000502:physiology / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000472:pathogenicity* / Q000648:ultrastructure*