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  Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion

Hanssen, E., Dekiwadia, C., Riglar, D., Rug, M., Lemgruber, L., Cowman, A. F., et al. (2013). Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion. Cellular Microbiology, 15(9), 1457-1472. doi:10.1111/cmi.12132.

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 Creators:
Hanssen, Eric1, Author
Dekiwadia, Chaitali2, Author
Riglar, David3, 4, Author
Rug, Melanie3, 4, Author
Lemgruber, Leandro5, Author
Cowman, Alan F.3, 4, Author
Cyrklaff, Marek5, Author
Kudryashev, Misha6, Author              
Frischknecht, Friedrich5, Author
Baum, Jake3, 4, Author
Ralph, Stuart A.2, Author
Affiliations:
1Advanced Microscopy Facility and Center of Excellence for Coherent X‐ray Science, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Vic., 3010 Australia, ou_persistent22              
2Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Vic., 3010 Australia, ou_persistent22              
3Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., 3052 Australia, ou_persistent22              
4Department of Medical Biology, University of Melbourne, Parkville, Vic., 3052 Australia, ou_persistent22              
5University of Heidelberg Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany, ou_persistent22              
6Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, 4058 Basel, Switzerland, ou_persistent22              

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 Abstract: 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 infectionincomplete, 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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Language(s): eng - English
 Dates: 2013-02-252012-11-292013-02-272013-03-222013-09
 Publication Status: Published in print
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1111/cmi.12132
PMID: 23461734
 Degree: -

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Title: Cellular Microbiology
Source Genre: Journal
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Publ. Info: Malden, MA : Blackwell Science
Pages: - Volume / Issue: 15 (9) Sequence Number: - Start / End Page: 1457 - 1472 Identifier: ISSN: 1462-5814
CoNE: https://pure.mpg.de/cone/journals/resource/959328105032