SRS13

SRS13 is a bradyzoite-upregulated, cyst wall-localized member of the SRS protein family in Toxoplasma gondii that contributes to the bradyzoite cyst surface but is dispensable for cyst wall formation, while serving as a protective vaccine antigen against chronic infection (PMID:29911257, PMID:38880692). Structurally, it comprises two SRS domains flanking a threonine-rich tandem-repeat mucin-like domain resembling CST1/SRS44, and is O-GalNAc glycosylated by the polypeptide GalNAc-transferases ppGalNAc-T2 and T3, consistent with its localization to the cyst wall (PMID:29911257). Loss-of-function experiments show that, unlike CST1, SRS13 is not required for normal cyst wall formation (PMID:29911257). Its immunogenicity underlies a functional role as a vaccine target: a SRS13 DNA vaccine delivered by electroporation elicits anti-SRS13 IgG, IFN-γ production and CD8+ IFN-γ-secreting T cells, and reduces brain tissue cyst burden after oral challenge with PRU strain cysts (PMID:38880692). Beyond its cyst wall localization, glycosylation, and antigenic properties, no additional molecular function of SRS13 has been characterized in the available corpus.

1. 2018 High

   Whether a mucin-domain SRS protein participates in the bradyzoite cyst wall was unknown; identifying SRS13 established a glycosylated, cyst wall-localized SRS protein that, unlike CST1, is not essential for cyst wall integrity.

   Evidence Glycoepitope antibody identification, immunofluorescence localization, stage-specific expression, O-GalNAc glycosylation assay with ppGalNAc-T2/T3, and gene knockout with cyst wall phenotype readout in T. gondii

   PMID:29911257

   Open questions at the time

   • The molecular function of SRS13 at the cyst wall and any binding partners are undefined
   • The consequence of its dispensability for bradyzoite persistence in vivo is not established
   • No structural model beyond domain architecture is available
2. 2024 Medium

   Whether SRS13 could be exploited immunologically was untested; a SRS13 DNA vaccine showed it is an immunogenic antigen that mobilizes humoral and CD8+ T-cell responses and reduces chronic-stage cyst burden.

   Evidence pVAX1-SRS13 DNA vaccination by intramuscular or intradermal electroporation in BALB/c mice with ELISA, Western blot, cytokine ELISA, flow cytometry, and oral PRU-strain challenge quantified by brain-cyst qPCR

   PMID:38880692

   Open questions at the time

   • Protection was shown in a single lab and mouse model; durability and cross-strain protection are not established
   • The relative contribution of antibody versus CD8+ T-cell responses to protection is not resolved
   • Whether native SRS13 is a target during natural infection immunity is untested

• The biochemical role of SRS13 at the cyst wall and its binding partners or host-interaction function remain unknown.
• No molecular activity or ligand has been identified for SRS13
• The functional significance of its mucin-like O-GalNAc glycosylation is uncharacterized