PRX1

TgPRX1 is a typical 2-cys peroxiredoxin of Toxoplasma gondii that detoxifies hydrogen peroxide as part of the parasite's antioxidant defence network (PMID:40059453). It localises to the cytoplasm and nucleus, and its individual deletion has no effect on the in vitro lytic cycle under standard conditions, yet renders parasites hypersensitive to exogenous H2O2; combined loss of TgPRX1 and the cytosolic peroxidase TgPRX2 impairs growth, establishing functional redundancy between the two enzymes (PMID:35328497, PMID:40059453). Beyond peroxide scavenging, TgPRX1 physically interacts with the histone lysine methyltransferase KMTox in an oxidation-enhanced manner, positioning it as a redox sensor that links oxidative stress to chromatin-level regulation (PMID:19017266). As a released antigen, recombinant TgPRX1 stimulates murine macrophages to produce IL-12p40 and IL-6 and activates NF-κB, giving it an additional immune-stimulating role (PMID:28448521).

1. 2008 Medium

   Whether peroxiredoxins do more than scavenge peroxide was addressed by showing TgPrx1 binds the histone methyltransferase KMTox with oxidation-enhanced affinity, positioning it as a redox sensor coupling oxidative stress to epigenetic regulation.

   Evidence Co-immunoprecipitation interaction assay plus in vitro methyltransferase activity under oxidizing and reducing conditions

   PMID:19017266

   Open questions at the time

   • Downstream target genes of KMTox-coupled regulation not defined in vivo
   • Single lab, no genetic validation of the interaction's function
   • Structural basis of oxidation-enhanced binding unknown
2. 2017 Medium

   A role for TgPrx1 beyond intracellular antioxidant function was revealed when the recombinant protein stimulated macrophages, establishing it as an immune-active released antigen.

   Evidence Recombinant protein stimulation of murine macrophages and RAW 264.7 cells with cytokine ELISA and NF-κB activation assay

   PMID:28448521

   Open questions at the time

   • Receptor mediating macrophage activation not identified
   • Uses recombinant protein rather than parasite-derived secreted protein
   • Physiological significance during infection not tested
3. 2022 Medium

   The requirement of TgPRX1 for the parasite lytic cycle was tested by CRISPR knockout, which showed no effect on infection, proliferation, or egress and confirmed a cyto-nuclear localisation distinct from mitochondrial TgPrx3.

   Evidence CRISPR-Cas9 knockout confirmed by PCR, IFAT, Western blot; immunofluorescence localisation; in vitro growth assays in strain Pru

   PMID:35328497

   Open questions at the time

   • Dispensability tested only under standard, non-stress conditions
   • No stress-challenge phenotype assessed here
   • Redundancy with other peroxiredoxins not tested
4. 2025 High

   The functional context of TgPRX1's dispensability was resolved by showing single knockouts are hypersensitive to exogenous H2O2 and that TgPRX1/TgPRX2 double deletion impairs growth, establishing genetic redundancy between the two cytosolic peroxidases in peroxide detoxification.

   Evidence CRISPR-Cas9 single and double knockouts with H2O2 susceptibility and in vitro growth assays

   PMID:40059453

   Open questions at the time

   • Molecular basis of redundancy (shared substrates/regulation) not defined
   • In vivo relevance during host infection not established
   • Relationship between peroxidase and KMTox/immune functions not integrated