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Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence

Chisholm, Scott A, McHugh, Emma, Lundie, Rachel, Dixon, Matthew WA, Ghosh, Sreejoyee, O'Keefe, Meredith, Tilley, Leann, Kalanon, Ming and de Koning-Ward, Tania F 2016, Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence, PLoS one, vol. 11, no. 2, pp. 1-21, doi: 10.1371/journal.pone.0149296.

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Title Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence
Formatted title Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence
Author(s) Chisholm, Scott A
McHugh, Emma
Lundie, Rachel
Dixon, Matthew WA
Ghosh, Sreejoyee
O'Keefe, Meredith
Tilley, Leann
Kalanon, Ming
de Koning-Ward, Tania FORCID iD for de Koning-Ward, Tania F orcid.org/0000-0001-5810-8063
Journal name PLoS one
Volume number 11
Issue number 2
Article ID e0149296
Start page 1
End page 21
Total pages 21
Publisher Public Library of Science
Place of publication San Fransisco, Calif.
Publication date 2016-02-17
ISSN 1932-6203
Keyword(s) Animals
Antigens, CD36
Cell Adhesion
Female
Gene Knockdown Techniques
Glucosamine
Immunity
Inflammation
Mice, Inbred C57BL
Parasites
Plasmodium berghei
Plasmodium falciparum
Protein Binding
Protein Transport
Protozoan Proteins
Virulence
Science & Technology
Multidisciplinary Sciences
Red blood cells
Infected erythrocytes
Malaria parasites
Host erythrocyte
Maurers clefts
In-vivo
Translocon
Summary Pathogenesis of malaria infections is linked to remodeling of erythrocytes, a process dependent on the trafficking of hundreds of parasite-derived proteins into the host erythrocyte. Recent studies have demonstrated that the Plasmodium translocon of exported proteins (PTEX) serves as the central gateway for trafficking of these proteins, as inducible knockdown of the core PTEX constituents blocked the trafficking of all classes of cargo into the erythrocyte. However, the role of the auxiliary component PTEX88 in protein export remains less clear. Here we have used inducible knockdown technologies in P. falciparum and P. berghei to assess the role of PTEX88 in parasite development and protein export, which reveal that the in vivo growth of PTEX88-deficient parasites is hindered. Interestingly, we were unable to link this observation to a general defect in export of a variety of known parasite proteins, suggesting that PTEX88 functions in a different fashion to the core PTEX components. Strikingly, PTEX88-deficient P. berghei were incapable of causing cerebral malaria despite a robust pro-inflammatory response from the host. These parasites also exhibited a reduced ability to sequester in peripheral tissues and were removed more readily from the circulation by the spleen. In keeping with these findings, PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial cell receptor, CD36. This suggests that PTEX88 likely plays a specific direct or indirect role in mediating parasite sequestration rather than making a universal contribution to the trafficking of all exported proteins.
Language eng
DOI 10.1371/journal.pone.0149296
Field of Research MD Multidisciplinary
Socio Economic Objective 0 Not Applicable
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30084633

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.