期刊
CELLULAR MICROBIOLOGY
卷 15, 期 9, 页码 1457-1472出版社
WILEY
DOI: 10.1111/cmi.12132
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资金
- National Center for Research Resources [5P41RR019664-08]
- National Institute of General Medical Sciences from the National Institutes of Health [8 P41 GM103445-08]
- National Health and Medical Research Council of Australia (NHMRC) [637340, APP1047085]
- Australian Research Council [DP120103161]
- Human Frontier Science Organisation (HFSP YI Program) [RGY0071/2011]
- Australian Synchrotron
- Australian Academy of Science
- US Department of Energy, Office of Biological and Environmental Research [DE-AC02-05CH11231]
- National Center for Research Resources of the National Institutes of Health [RR019664]
- US Department of Energy, Office of Science
- Pratt Foundation through the University of Melbourne
- OzeMalaR Network
- University of Heidelberg cluster of excellence CellNetworks
- CINA grant from SystemX.ch
- Henning Stahlberg (University of Basel)
- Australian Research Council (ARC) [FT100100112, FT0990350]
Erythrocyte invasion by merozoites forms of the malaria parasite is a key step in the establishment of human malaria disease. To date, efforts to understand cellular events underpinning entry have been limited to insights from non-human parasites, with no studies at sub-micrometer resolution undertaken using the most virulent human malaria parasite, Plasmodium falciparum. This leaves our understanding of the dynamics of merozoite sub-cellular compartments during infection incomplete, in particular that of the secretory organelles. Using advances in P. falciparum merozoite isolation and new imaging techniques we present a three-dimensional study of invasion using electron microscopy, cryo-electron tomography and cryo-X-ray tomography. We describe the core architectural features of invasion and identify fusion between rhoptries at the commencement of invasion as a hitherto overlooked event that likely provides a critical step that initiates entry. Given the centrality of merozoite organelle proteins to vaccine development, these insights provide a mechanistic framework to understand therapeutic strategies targeted towards the cellular events of invasion.
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