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Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design

McCoubrie, Joanne E., Miller, Susanne K., Sargeant, Tobias, Good, Robert T., Hodder, Anthony N., Speed, Terence P., de Koning-Ward, Tania and Crabb, Brendan S. 2007, Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design, Infection and immunity, vol. 75, no. 12, pp. 5565-5574.

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Title Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design
Formatted title Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design
Author(s) McCoubrie, Joanne E.
Miller, Susanne K.
Sargeant, Tobias
Good, Robert T.
Hodder, Anthony N.
Speed, Terence P.
de Koning-Ward, Tania
Crabb, Brendan S.
Journal name Infection and immunity
Volume number 75
Issue number 12
Start page 5565
End page 5574
Publisher American Society for Microbiology
Place of publication Washington, D.C.
Publication date 2007-12
ISSN 0019-9567
1098-5522
Summary Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases of Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place of the canonical cysteine. The human malaria parasite Plasmodium falciparum possesses six “serine-type” (SERA1 to SERA5 and SERA9) and three “cysteine-type” (SERA6 to SERA8) SERAs. Here, we investigate the importance of the serine-type SERAs to blood-stage parasite development and examine the extent of functional redundancy among this group. We attempted to knock out the four P. falciparum serine-type SERA genes that have not been disrupted previously. SERA1, SERA4, and SERA9 knockout lines were generated, while only SERA5, the most strongly expressed member of the SERA family, remained refractory to genetic deletion. Interestingly, we discovered that while SERA4-null parasites completed the blood-stage cycle normally, they exhibited a twofold increase in the level of SERA5 mRNA. The inability to disrupt SERA5 and the apparent compensatory increase in SERA5 expression in response to the deletion of SERA4 provides evidence for an important blood-stage function for the serine-type SERAs and supports the notion of functional redundancy among this group. Such redundancy is consistent with our phylogenetic analysis, which reveals a monophyletic grouping of the serine-type SERAs across the genus Plasmodium and a predominance of postspeciation expansion. While SERA5 is to some extent further validated as a target for vaccine and drug development, our data suggest that the expression level of other serine-type SERAs is the only barrier to escape from anti-SERA5-specific interventions.
Language eng
Field of Research 110803 Medical Parasitology
Socio Economic Objective 970111
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2007, American Society for Microbiology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007479

Document type: Journal Article
Collections: School of Medicine
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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.