bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2026–08–30
seven papers selected by
Lakesh Kumar, BITS Pilani
  1. A Live Attenuated AP2X-1-Deficient Toxoplasma Strain Confers Protective Immunity Against Acute and Chronic Toxoplasmosis in a Murine Model.
  2. Dual apical methyltransferases orchestrate motility initiation in apicomplexan parasites.
  3. ROP64-Deficient Toxoplasma gondii Strain Confers Protection Against Acute and Chronic Toxoplasmosis in Mice.
  4. Affino-Proteomic Analysis of Bumped Kinase Inhibitor BKI-1708 in Toxoplasma gondii and Human Fibroblast Host Cells.
  5. Photodynamic Therapy for Toxoplasma gondii Infections Using Rose Bengal.
  6. Lipid metabolism and chromatin-associated sirtuin-dependent epigenetic reprogramming in cancer.
  7. SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation.
  1. Animals (Basel). 2026 Aug 07. pii: 2453. [Epub ahead of print]16(16):
    A Live Attenuated AP2X-1-Deficient Toxoplasma Strain Confers Protective Immunity Against Acute and Chronic Toxoplasmosis in a Murine Model.
    Wen-Bo Hao, Li-Xiu Sun, Ru-Shi Tu, Zhi Zheng, Chen-Ran Tian, Xing-Quan Zhu, Xiao-Nan Zheng.
      Toxoplasma gondii is an obligate intracellular apicomplexan parasite that poses serious risks to immunocompromised individuals and the global livestock industry. Our previous study showed that AP2X-1 regulates stage conversion and virulence of T. gondii; however, whether AP2X-1-deficient strains can serve as live-attenuated vaccine candidates is unknown. Here, we evaluated the in vivo virulence, protective efficacy, and induced immunity of the ap2X-1 knockout strain PruΔap2X-1. In Kunming mice, infection with even the highest tested dose (5 × 106 tachyzoites) of PruΔap2X-1 resulted in 100% survival without detectable brain cysts. Vaccination with 106 PruΔap2X-1 tachyzoites conferred complete protection (100% survival) against acute challenge with homologous type II Pru or heterologous ToxoDB#9 PYS strains, whereas control mice exhibited only 0% to 16.7% survival. Moreover, immunized mice orally challenged with Pru cysts showed 100% survival, and no brain cysts were detected under the conditions tested, compared with only 30% survival in control mice challenged with 10 cysts and no survival with 40 cysts. The vaccination induced a Th1-biased response as evidenced by significantly elevated T. gondii-specific total IgG, IgG2a, and the Th1 cytokines IFN-γ and IL-2, along with a significantly reduced IgG1/IgG2a ratio. Collectively, the attenuated PruΔap2X-1 strain generates strong protective immunity against acute and chronic infection with low-virulence strains (the type II Pru and ToxoDB#9 PYS), as well as partial protection against the hypervirulent type I RH strain, positioning it as a potential candidate for a live-attenuated vaccine, with a favorable safety profile observed under the experimental conditions.
    Keywords:  PruΔap2X-1; Th1 immune response; Toxoplasma gondii; acute and chronic infection; live-attenuated vaccine
    DOI:  https://doi.org/10.3390/ani16162453
  2. Nat Commun. 2026 08 26. pii: 9068. [Epub ahead of print]17(1):
    Dual apical methyltransferases orchestrate motility initiation in apicomplexan parasites.
    Peipei Qin, Thrishla Kumar, Oliwia Koczy, Wei Li, Ignasi Forne, Simone Mattei, Elena Jimenez-Ruiz.
      Apicomplexan parasites such as Toxoplasma gondii initiate motility through rapid, spatially confined cytoskeletal activation at their apical end. While calcium-, lipid-, and kinase-based signalling pathways have been partially elucidated, how these cues are translated into mechanical force remains unclear. Here, we uncover a dual methyltransferase mechanism that orchestrates this process. We characterise TgPCKMT, a PreConoidal ring-associated lysine (K) MethylTransferase, as an essential upstream regulator of motility. TgPCKMT anchors the actin nucleator Formin-1 (TgFRM1) at the conoid, enabling conoid protrusion and F-actin assembly. Loss of TgPCKMT abolishes TgFRM1 recruitment, blocks conoid extrusion, and arrests invasion and egress despite preserved conoid structure. In contrast, the apical methyltransferase TgAKMT, previously linked to motility through recruitment of the glideosome-associated connector (TgGAC), acts downstream, disengaging from the conoid upon activation and likely promoting TgGAC-dependent force transmission. TgPCKMT depletion prevents TgAKMT translocation, revealing that actin assembly and lysine methylation are mechanistically coupled. Together, these findings define a two-step methylation regulatory module that coordinates actin nucleation with force propagation, uncovering methylation as a central regulatory axis for motility initiation in apicomplexan parasites.
    DOI:  https://doi.org/10.1038/s41467-026-77078-y
  3. Microorganisms. 2026 Aug 06. pii: 1725. [Epub ahead of print]14(8):
    ROP64-Deficient Toxoplasma gondii Strain Confers Protection Against Acute and Chronic Toxoplasmosis in Mice.
    Zhi Zheng, Shi-Bo Huang, Yi-Rong Ma, Wen-Bo Hao, Xiao-Nan Zheng, Hong-Yu Song, Xing-Quan Zhu.
      Toxoplasmosis, caused by Toxoplasma gondii, remains an important zoonotic disease affecting both human and animal health, particularly in immunocompromised individuals and during pregnancy. Current treatments are unable to eliminate latent tissue cysts and are further limited by adverse effects and prolonged treatment regimens, highlighting the need for effective vaccines. In this study, we evaluated the virulence attenuation and protective efficacy of a CRISPR-Cas9-generated rhoptry protein 64 knockout strain (RHΔrop64) as a live attenuated vaccine candidate in Kunming mice. RHΔrop64 exhibited markedly reduced virulence, and mice tolerated doses of up to 1 × 102 tachyzoites without obvious clinical signs. Immunization provided substantial protection against acute challenge with the parental RHΔku80 and ToxoDB#9 (PYS) strains at 30 days post-vaccination and partial protection against type II (Pru) tachyzoites. In addition, all immunized mice survived following oral challenge with 10 or 40 Pru cysts and exhibited reduced brain cyst burdens among surviving mice. Vaccination also induced measurable humoral and cytokine responses, characterized by increased levels of T. gondii-specific IgG and cytokines that were maintained for at least 75 days post-vaccination. These results suggest that RHΔrop64 has the potential to serve as a live attenuated vaccine candidate, providing substantial, although incomplete, protection against acute challenge with the three T. gondii strains tested and being associated with reduced brain cyst burdens among surviving mice following chronic challenge. Further evaluation is required to determine its safety and applicability as a vaccine candidate for food-producing animals and cats.
    Keywords:  ROP64; Toxoplasma gondii; cyst burden; immune response; live attenuated vaccine; virulence attenuation
    DOI:  https://doi.org/10.3390/microorganisms14081725
  4. Microorganisms. 2026 Jul 23. pii: 1608. [Epub ahead of print]14(8):
    Affino-Proteomic Analysis of Bumped Kinase Inhibitor BKI-1708 in Toxoplasma gondii and Human Fibroblast Host Cells.
    Maria Cristina Ferreira de Sousa, Joachim Müller, Manfred Heller, Anne-Christine Uldry, Sophie Braga-Lagache, Kayode K Ojo, Wesley C Van Voorhis, Andrew Hemphill.
      Bumped kinase inhibitor 1708 (BKI-1708), previously demonstrated to target apicomplexan kinases and CDPK1 and MAPKL1, exhibits remarkable activity against Toxoplasma gondii infection both in vitro and in vivo. Notably, BKI-1708 does not affect the viability of mammalian cells. Upon exposure to BKI-1708, T. gondii tachyzoites form large multinucleated complexes named baryzoites and remain trapped within host cells. In this study, proteins binding to BKI-1708 were identified in soluble extracts of T. gondii ME49 tachyzoites and human foreskin fibroblasts (HFF) using differential affinity chromatography coupled to mass spectrometry (DAC-MS). Beyond kinases, secondary interactions in T. gondii involved the binding of proteins associated with cell division, cytoskeleton, vesicular trafficking, secretory organelles, and transcriptional and translational regulators. In non-infected HFFs, BKI-1708 interactors included cytoskeletal regulators along with multiple RNA/DNA-binding proteins. Upon infection, this profile shifted, with cytoskeletal components no longer detected, while nucleic acid-binding proteins remained present, consistent with infection-induced chromatin and transcriptional remodeling. These results suggest that multi-target interference could contribute to the impaired cytokinesis and the formation of multinucleated baryzoites, aligning with the concept that antiprotozoal drugs exert efficacy through coordinated perturbation of multiple cellular processes rather than a single dominant target.
    Keywords:  Toxoplasma gondii; affinity chromatography; bumped kinase inhibitors; drug targets; drug treatment; proteomics
    DOI:  https://doi.org/10.3390/microorganisms14081608
  5. Luminescence. 2026 Aug;41(8): e70583
    Photodynamic Therapy for Toxoplasma gondii Infections Using Rose Bengal.
    Wen Li, Jiating Chen, Jie Li, Qingqing Zhang, Jihong Chen, Pengfei Zhang, Fufeng Liu.
      Toxoplasma gondii is a globally prevalent obligate intracellular protozoan parasite that causes severe zoonotic disease. Given the limitations of conventional drug therapies, including susceptibility to drug resistance, and significant toxic side effects, this study aimed to evaluate the efficacy of photodynamic therapy (PDT) combined with the classic photosensitizer Rose Bengal in eradicating T. gondii tachyzoites, whilst elucidating its underlying mechanism of action. Experimental results demonstrate that Rose Bengal efficiently induces the generation of both Type I and Type II reactive oxygen species (ROS) under light exposure, exhibiting potent phototoxic killing effects against T. gondii. Further transcriptomic analysis revealed that this mechanism involves Rose Bengal disrupting metabolic and motility-related signaling pathways in T. gondii, thereby programmatically inducing T. gondii cell death. Both in vivo and in vitro experiments confirmed that this approach effectively eradicates T. gondii while demonstrating favorable biosafety. This study provides experimental evidence for developing novel photodynamic therapies against T. gondii, expanding the application potential of photodynamic therapy in combating parasitic infections.
    Keywords:   Toxoplasma gondii ; Rose Bengal; photodynamic therapy; reactive oxygen species; transcriptomic profiling
    DOI:  https://doi.org/10.1002/bio.70583
  6. Mol Biol Rep. 2026 Aug 25. pii: 1458. [Epub ahead of print]53(1):
    Lipid metabolism and chromatin-associated sirtuin-dependent epigenetic reprogramming in cancer.
    Francisco Alejandro Lagunas-Rangel.
      Lipids are essential components of cancer biology, serving not only as sources of energy and biomass but also as signalling molecules that influence gene regulation and cellular plasticity. Increasing evidence suggests that lipid metabolic rewiring can shape epigenetic states through the activity of sirtuins, a family of NAD+-dependent enzymes with deacetylase, deacylase and ADP-ribosyltransferase activities that couple metabolic cues to chromatin regulation. This narrative review examines how alterations in fatty acid oxidation, lipid uptake, cholesterol metabolism and lipid-derived metabolites converge on the sirtuin family of NAD+-dependent enzymes to regulate epigenetic states in cancer. Lipid metabolism shapes sirtuin function by influencing NAD+/NADH balance, acetyl-CoA availability and the production of diverse acyl-CoA species, thereby modulating histone acetylation, non-canonical lysine acylations and DNA methylation programmes. In parallel, lipid metabolites can directly regulate sirtuin abundance, activity and subcellular localization, with context-dependent consequences for chromatin regulation and transcriptional plasticity. Emerging evidence indicates that this lipid-sirtuin-epigenetic axis contributes to metabolic adaptation and tumour cell fitness, stemness, antitumour immunity and metastatic dissemination. The dual nature of sirtuin signalling is also discussed, as these enzymes can either promote or constrain tumour progression depending on the metabolic and microenvironmental context. Therapeutic opportunities targeting lipid metabolism and sirtuins are considered, together with the potential of lipid, sirtuin and epigenetic signatures as biomarkers for prognosis, patient stratification and precision oncology.
    Keywords:  Cancer stem cells; Chromatin regulation; Fatty acid oxidation; Histone deacylation; Tumour microenvironment
    DOI:  https://doi.org/10.1007/s11033-026-12653-6
  7. Proc Natl Acad Sci U S A. 2026 Sep;123(35): e2532225123
    SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation.
    Kaeden K Hill, Ashley P Barry, Nicolas M Reinoso-Vizcaino, Lauren E Haynes, Emmanuela N Bonglack, Davis F Ferreira, Sara E Miller, Matthew D Hirschey, Lillian W Chiang, Stacy Remiszewski, Micah A Luftig.
      Sirtuin-2 (SIRT2) is a cellular deacylase, regulating cell cycle progression and metabolic homeostasis. Recently, SIRT2 has emerged as a target with both anticancer and antiviral potential. However, the role and targetability of SIRT2 in viral-driven cancers remains unexplored. Epstein-Barr virus (EBV) is a ubiquitous herpesvirus with oncogenic potential that establishes latency in B lymphocytes and is typically controlled by a robust T cell immune response. In settings that compromise this response, such as immune suppression following transplant, EBV can cause B cell lymphomas. With broad immunosuppression and varying response rates limiting the effectiveness of existing lymphoma therapeutics, new strategies are necessary. Here, we report that SIRT2-selective compounds block EBV-mediated B cell transformation and EBV or mitogen-driven B cell division in vitro. SIRT2 modulation significantly alters gene expression and metabolism of EBV-infected B cells, reducing mitochondrial respiration, driving mitochondrial swelling, and inducing nutrient stress and autophagy. Treatment with SIRT2 modulators drives hyperacetylation of targets involved in lipid metabolism, central carbon metabolism, and oxidative phosphorylation. EBV-positive and EBV-negative B cell lymphomas rely on glycolysis to avoid cell death after SIRT2 modulation, revealing a metabolic vulnerability that can be harnessed to kill lymphoma cells. Overall, we have identified how SIRT2 could be implicated as a target of therapeutic potential for B cell lymphomas, while also defining fundamental roles for extranuclear lysine acetylation in regulating B cell proliferation and metabolism.
    Keywords:  B cell; Epstein–Barr virus; lymphoma; mitochondria; sirtuin
    DOI:  https://doi.org/10.1073/pnas.2532225123
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