4D analysis of malaria parasite invasion offers insights into erythrocyte membrane remodeling and parasitophorous vacuole formation

Niall D Geoghegan; Cindy Evelyn; Lachlan W Whitehead; Michal Pasternak; Phoebe McDonald; Tony Triglia; Danushka S Marapana; Daryan Kempe; Jennifer K Thompson; Michael J Mlodzianoski; Julie Healer; Mate Biro; Alan F Cowman; Kelly L Rogers

Journal article

4D analysis of malaria parasite invasion offers insights into erythrocyte membrane remodeling and parasitophorous vacuole formation

Niall D Geoghegan, Cindy Evelyn, Lachlan W Whitehead, Michal Pasternak, Phoebe McDonald, Tony Triglia, Danushka S Marapana, Daryan Kempe, Jennifer K Thompson, Michael J Mlodzianoski, Julie Healer, Mate Biro, Alan F Cowman, Kelly L Rogers

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021

DOI: 10.1038/s41467-021-23626-7

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Abstract

Host membrane remodeling is indispensable for viruses, bacteria, and parasites, to subvert the membrane barrier and obtain entry into cells. The malaria parasite Plasmodium spp. induces biophysical and molecular changes to the erythrocyte membrane through the ordered secretion of its apical organelles. To understand this process and address the debate regarding how the parasitophorous vacuole membrane (PVM) is formed, we developed an approach using lattice light-sheet microscopy, which enables the parasite interaction with the host cell membrane to be tracked and characterized during invasion. Our results show that the PVM is predominantly formed from the erythrocyte membrane, which undergoe..

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University of Melbourne Researchers

Niall Geoghegan Author Medical Biology (w.e.h.i.)

Alan Cowman Author Medical Biology (w.e.h.i.)

Kelly Rogers Author Medical Biology (w.e.h.i.)

Julie Healer Author Medical Biology (w.e.h.i.)

Tony Triglia Author Medical Biology (w.e.h.i.)

Grants

Awarded by EMBO Long Term Fellowship

Awarded by Sir Henry Wellcome Fellowship

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by NHMRC

Funding Acknowledgements

We thank Brad Sleebs for providing Compound 1 and Kitsanapong Reaksudsan for assistance in maintaining parasite cultures. We also thank Nina Tubau for assistance with data processing. The lattice light-sheet referenced in this research was used under license from Howard Hughes Medical Institute, Janelia Research Campus. We acknowledge the Australian Red Cross Blood Service for providing blood. This work was supported by an EMBO Long Term Fellowship ALTF 793-2016 and Sir Henry Wellcome Fellowship 206515_Z_17_Z to M.P. This work was also supported by grants from the National Health and Medical Research Council (NHMRC), APP1177431 to D.M, and NHMRC APPs 1121178, 1092789 and 1117288 to A.F.C.