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Host cell remodelling in malaria parasites: a new pool of potential drug targets

Gilson, Paul, Chisholm, Scott, Crabb, Brendan S. and De Koning-Ward, Tania 2017, Host cell remodelling in malaria parasites: a new pool of potential drug targets, International journal of parasitology, vol. 47, no. 2-3, pp. 119-127, doi: 10.1016/j.ijpara.2016.06.001.

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Title Host cell remodelling in malaria parasites: a new pool of potential drug targets
Author(s) Gilson, Paul
Chisholm, Scott
Crabb, Brendan S.
De Koning-Ward, TaniaORCID iD for De Koning-Ward, Tania orcid.org/0000-0001-5810-8063
Journal name International journal of parasitology
Volume number 47
Issue number 2-3
Start page 119
End page 127
Total pages 9
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2017-02
ISSN 0020-7519
1879-0135
Keyword(s) host cell modification
malaria
plasmodium falciparum
protein export
translocon
virulence
Science & Technology
Life Sciences & Biomedicine
Parasitology
RED-BLOOD-CELLS
SIGNAL PEPTIDE PEPTIDASE
FALCIPARUM-INFECTED ERYTHROCYTES
PLASMODIUM EXPORT ELEMENT
PARASITOPHOROUS VACUOLE
PLASMEPSIN V
IN-VIVO
SMALL MOLECULES
Summary When in their human hosts, malaria parasites spend most of their time housed within vacuoles inside erythrocytes and hepatocytes. The parasites extensively modify their host cells to obtain nutrients, prevent host cell breakdown and avoid the immune system. To perform these modifications, malaria parasites export hundreds of effector proteins into their host cells and this process is best understood in the most lethal species to infect humans, Plasmodium falciparum. The effector proteins are synthesized within the parasite and following a proteolytic cleavage event in the endoplasmic reticulum and sorting of mature proteins into the correct vesicular trafficking pathway, they are transported to the parasite surface and released into the vacuole. The effector proteins are then unfolded before extrusion across the vacuole membrane by a unique translocon complex called Plasmodium translocon of exported proteins. After gaining access to the erythrocyte cytoplasm many effector proteins continue their journey to the erythrocyte surface by utilising various membranous structures established by the parasite. This complex trafficking pathway and a large number of the effector proteins are unique to Plasmodium parasites. This pathway could, therefore, be developed as new drug targets given that protein export and the functional role of these proteins are essential for parasite survival. This review explores known and potential drug targetable steps in the protein export pathway and strategies for discovering novel drug targets.
Language eng
DOI 10.1016/j.ijpara.2016.06.001
Field of Research 110803 Medical Parasitology
0605 Microbiology
0608 Zoology
0707 Veterinary Sciences
Socio Economic Objective 920108 Immune System and Allergy
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Australian Society for Parasitology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30084871

Document type: Journal Article
Collection: Molecular and Medical Research
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