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

McCoubrie, JE; Miller, SK; Sargeant, T; Good, RT; Hodder, AN; Speed, TP; de Koning-Ward, TF; Crabb, BS

Author(s): McCoubrie, JE; Miller, SK; Sargeant, T; Good, RT; Hodder, AN; Speed, TP; de Koning-Ward, TF; Crabb, BS;
Details: Publication Year 2007-12,Volume 75,Issue #12,Page 5565-5574
Journal Title: INFECTION AND IMMUNITY
Publication Type: Journal Article
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 SER,45 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 SER,44-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: AMER SOC MICROBIOLOGY
Keywords: SERA MULTIGENE FAMILY; MALARIA PARASITES; LIFE-CYCLE; GENE; EXPRESSION; RECOMBINATION; LOCALIZATION; TRANSFECTION; INVASION; GENOME
Publisher's Version: https://doi.org/10.1128/IAI.00405-07
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-12-01 12:00:00