PPM2B

PPM2B is a PPM (protein phosphatase 2C)-family serine/threonine phosphatase of Toxoplasma gondii that localizes mainly to the tachyzoite cytoplasm (PMID:39461506). Genetic ablation of PPM2B does not impair intracellular replication, and neither single knockout nor combined PPM2A/PPM2B double knockout reduces virulence in mice, indicating the phosphatase is dispensable for essential replication and acute pathogenesis (PMID:39461506). Its loss does, however, reduce plaque size relative to control parasites, assigning PPM2B a role in overall parasite fitness or growth efficiency rather than in the replication cycle itself (PMID:39461506). Beyond these localization and loss-of-function observations, no substrates, interacting partners, or catalytic mechanism have been characterized in the available corpus.

1. 2024 Medium

   Establishing where PPM2B acts was the first step in assigning function; endogenous tagging placed this PPM-family phosphatase in the tachyzoite cytoplasm.

   Evidence Endogenous C-terminal 10HA tagging with immunofluorescence localization in RHΔku80

   PMID:39461506

   Open questions at the time

   • No substrates or dephosphorylation targets identified
   • Catalytic activity not directly demonstrated in vitro
   • No interacting partners defined
2. 2024 Medium

   To test whether PPM2B is required for parasite propagation and disease, knockouts were assessed, showing the phosphatase is dispensable for intracellular replication and acute virulence.

   Evidence CRISPR-Cas9 knockout with intracellular replication assay and mouse virulence experiments, including PPM2A/PPM2B double knockout, versus RHΔhxgprt control

   PMID:39461506

   Open questions at the time

   • Negative in vivo result does not exclude a role under other conditions or in chronic/cyst stages
   • Possible functional redundancy with other phosphatases not fully excluded despite the double knockout
   • Molecular basis of dispensability unknown
3. 2024 Medium

   A subtler phenotype was sought to reconcile the absence of a replication defect; plaque assays revealed reduced plaque size, implicating PPM2B in parasite fitness rather than the replication cycle per se.

   Evidence Plaque assay comparing Δppm2b and double-knockout strains to RHΔhxgprt control

   PMID:39461506

   Open questions at the time

   • Which step of the lytic cycle (invasion, egress, motility) underlies the plaque defect is unresolved
   • The signaling pathway or substrate linking PPM2B to growth efficiency is unknown

• The physiological substrates, catalytic activity, and the molecular basis of the fitness defect for PPM2B remain unresolved.
• No substrate or interactome identified
• Mechanistic link between phosphatase activity and reduced plaque size undefined
• Function in non-RH strains and chronic stages uncharacterized