Affiliation:
1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
71 articles.
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