bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2026–07–19
nine papers selected by
Lakesh Kumar, BITS Pilani
  1. TgRON3 Links the Moving Junction to Microneme Secretion and Parasite Motility in Toxoplasma gondii.
  2. The Live-Attenuated PruΔgra47 Strain of Toxoplasma gondii Confers Protective Immunity Against Acute and Chronic Toxoplasmosis in Mice.
  3. A pooled image-based CRISPR screen identifies EAF1 as a T. gondii modulator of ESCRT subversion.
  4. Toxoplasma gondii Microneme Protein 3 (TgMIC3): Computational Probing for Improved Vaccine Design.
  5. The SIRT Family: Subcellular Localization and Main Functions.
  6. Interference of phototherapy with blue LED light on the behaviour of mice infected with Toxoplasma gondii.
  7. Structural dissection of apicomplexan gliding motility.
  8. Site-Specific incorporation of lysine acetyl-methylation into proteins.
  9. The pyruvate dehydrogenase complex at the crossroads of cancer metabolism and cell death.
  1. FASEB J. 2026 Jul 31. 40(14): e72079
    TgRON3 Links the Moving Junction to Microneme Secretion and Parasite Motility in Toxoplasma gondii.
    Yanqun Pei, Jing Peng, Zhu Ying, Zifu Zhu, Yong Fu, Qun Liu, Jing Liu.
      Toxoplasma gondii invades host cells through a highly coordinated process centered on the moving junction (MJ). Although core MJ components are essential for efficient invasion, parasites lacking these factors retain limited invasive capacity, suggesting the involvement of additional regulatory elements. To identify such factors, we applied proximity labeling to systematically characterize proteins associated with the MJ component TgRON8. This strategy identified multiple essential proteins, including TgRON3 and TgAPH. Disruption of either gene resulted in a pronounced defect in host cell invasion. Structural modeling and co-immunoprecipitation assays demonstrated that TgRON3 associates with the canonical MJ proteins TgRON2 and TgRON4. In addition, TgRON3 also interacted with two previously uncharacterized transmembrane proteins, TgHTM7 and TgHTM9. Deletion of either TgHTM7 or TgHTM9 led to reduced microneme secretion and substantial transcriptional downregulation of invasion-associated adhesins, including MIC2 and M2AP. Consistent with these molecular defects, parasites lacking TgHTM7 or TgHTM9 exhibited impaired motility, host cell attachment, invasion, and plaque formation. Together, our findings define a regulatory module that links MJ-associated components to microneme secretion and parasite motility, providing new insights into the molecular mechanisms governing T. gondii invasion.
    Keywords:   Toxoplasma gondii ; host cell invasion; microneme secretion; moving junction; parasite motility
    DOI:  https://doi.org/10.1096/fj.202600838RR
  2. Animals (Basel). 2026 Jun 25. pii: 1964. [Epub ahead of print]16(13):
    The Live-Attenuated PruΔgra47 Strain of Toxoplasma gondii Confers Protective Immunity Against Acute and Chronic Toxoplasmosis in Mice.
    Chen-Ran Tian, Xing Tian, Shu-Min Zhao, Zhi Zheng, Wen-Bo Hao, Xing-Quan Zhu, Xiao-Nan Zheng.
      Toxoplasma gondii is an apicomplexan parasite that causes toxoplasmosis, a widespread zoonotic disease leading to serious public health concerns and economic losses to animal husbandry. Currently, highly effective vaccines against toxoplasmosis remain unavailable. This study aimed to investigate the safety, immunogenicity, and protective efficacy of the gra47-deficient mutant strain PruΔgra47 as a live-attenuated vaccine candidate. We evaluated the virulence of PruΔgra47 in a mouse model, determined the optimal immunization dose, and measured serum antibody levels and cytokine profiles. Then, mice immunized with PruΔgra47 were challenged with different T. gondii strains to assess protection against acute and chronic infection. PruΔgra47 displayed significantly attenuated virulence and its ability to form cysts was weakened. Vaccination with 5 × 106 tachyzoites elicited predominantly Th1-skewed immune responses. Immunization with PruΔgra47 provided complete protection against challenge infection with relatively low-virulent PYS strain and homologous Pru strain, prolonged survival against the highly virulent RH strain, and achieved a 90% survival rate with reduced brain cyst burden under chronic challenge. In conclusion, PruΔgra47 is relatively safe and immunogenic in the murine model, and is worth being evaluated in food-producing animals and cats.
    Keywords:  PruΔgra47; Toxoplasma gondii; acute and chronic infection; immune responses; live-attenuated vaccine
    DOI:  https://doi.org/10.3390/ani16131964
  3. bioRxiv. 2026 Jul 09. pii: 2026.07.08.737057. [Epub ahead of print]
    A pooled image-based CRISPR screen identifies EAF1 as a T. gondii modulator of ESCRT subversion.
    Einar B Olafsson, Christophe-Sebastien Arnold, Jacob A Kellermeier, Patrick A Rimple, Hargobinder Kaur, Yifan Wang, Jonathan Z Sexton, Staffan Svärd, Vern B Carruthers, Matthew J O'Meara.
      Intracellular pathogens remodel host cells by redirecting cellular machinery to the host-pathogen interface. The protozoan parasite Toxoplasma gondii co-opts host ESCRT proteins at the parasitophorous vacuole membrane (PVM), where they support budding of host-derived vesicles into the vacuole. Yet the parasite effectors that direct this process remain largely unknown. Here we developed spaCR ( s patial p henotype a nalysis of CR ISPR-Cas9 screens), a pooled image-based screening framework that combines deep-learning classification of single-cell spatial phenotypes with well-level barcode genotyping and regression-based deconvolution of gene effects. Screening T. gondii secretory proteins recovered the known TSG101 recruiter GRA14 and identified an uncharacterized effector, ESCRT-association factor 1 (EAF1), that promoted TSG101 recruitment to the PVM. Targeted deletion confirmed its role across Type I and II lineages, and IP-MS recovered ESCRT-I and ESCRT-III components, including TSG101. Together, these findings identify EAF1 as an ESCRT-associated parasite effector and establish spaCR as a general framework for linking CRISPR perturbations to spatial phenotypes.
    DOI:  https://doi.org/10.64898/2026.07.08.737057
  4. Iran J Parasitol. 2026 Jan-Mar;21(1):21(1): 105-116
    Toxoplasma gondii Microneme Protein 3 (TgMIC3): Computational Probing for Improved Vaccine Design.
    Masoud Foroutan, Hamidreza Majidiani, Fatemeh Ghaffarifar, Elaheh Karimzadeh-Soureshjani, Amir Karimipour-Saryazdi, Ali Dalir Ghaffari, John Horton.
       Background: Microneme protein 3 (MIC3) is a key adhesion molecule in Toxoplasma gondii that is expressed during multiple stages of infection. We aimed to computationally characterize the immunological and structural features of the T. gondii MIC3 protein to assess its potential suitability as a vaccine candidate.
    Methods: A comprehensive set of bioinformatics tools and web servers was employed to predict the physicochemical properties, allergenicity, antigenicity, solubility, post-translational modification sites, subcellular localization, transmembrane domains, signal peptides, secondary and tertiary structures, potential B- and T-lymphocyte epitopes, and simulated immune responses of the TgMIC3 protein.
    Results: A total of 75 post-translational modification sites were predicted in TgMIC3. Furthermore, secondary structure analysis using GOR IV, SOPMA, and NetSurfP-3.0 indicated that random coils and extended strands were the predominant structural elements. In addition, several high-affinity B- and T-cell epitopes were identified across the protein sequence. Subsequent structural validation revealed that 82.91% and 98.60% of residues were located in favored regions in the initial and refined 3D models, respectively. The findings of the allergenicity and antigenicity assessments indicated that the MIC3 antigen seemed to be a non-allergen with an immunogenic nature. Moreover, immune simulation using the C-ImmSim server demonstrated that TgMIC3 could induce robust humoral and cell-mediated immune responses following three simulated antigen administrations. Conclusion: This study provides foundational computational evidence supporting the potential of TgMIC3 as a vaccine antigen and offers a useful framework for future experimental investigations targeting vaccine development against acute and latent toxoplasmosis.
    Keywords:  Bioinformatics; In silico; Microneme proteins; Toxoplasma gondii; Vaccine
    DOI:  https://doi.org/10.18502/ijpa.v21i1.21639
  5. Int J Mol Sci. 2026 Jul 06. pii: 6042. [Epub ahead of print]27(13):
    The SIRT Family: Subcellular Localization and Main Functions.
    Ping Quan, Christoph Schatz, Daria Maria Filippini, Johannes Haybaeck.
      The mammalian sirtuins (SIRTs), consisting of seven members (SIRT 1-7), are NAD+-dependent histone deacetylases (HDACs). Similar to other classical NAD+-independent HDACs, SIRTs regulate a wide range of key biological processes by deacetylating both histone and non-histone proteins. By linking cellular metabolism to tissue homeostasis, SIRTs play important roles in physiological regulation and are often deregulated in many human diseases including diabetes, neurodegeneration and cancer, particularly sarcomas. Here, we reviewed the expression and roles of SIRTs, especially the most studied family member SIRT 1, across several types of human sarcomas, including both bone and soft tissues sarcomas. We also discussed the clinical relevance of SIRTs and the potential of their modulation as a therapeutic strategy in sarcomas.
    Keywords:  expression; prognosis indicator; sarcoma; sirtuin (SIRT)
    DOI:  https://doi.org/10.3390/ijms27136042
  6. PLoS One. 2026 ;21(7): e0353740
    Interference of phototherapy with blue LED light on the behaviour of mice infected with Toxoplasma gondii.
    Marina Monteiro de Castro Burle, Ben-Hur Araújo Batista da Silva, Débora Nonato Miranda de Toledo, Lauro de Assis Duarte Junior, Rodrigo Fernando Bianchi, Érica S Martins-Duarte, André Talvani, Cristiano Schetini de Azevedo.
      Toxoplasma gondii is an intracellular protozoan capable of promoting physiological and behavioural changes in hosts. When female mammals acquire T. gondii for the first time during pregnancy, Congenital Toxoplasmosis (CT) can occur, posing a significant risk to the foetus. Due to challenges in diagnosing and treating CT, a new blue LED light therapy (BLLT) was proposed to eliminate parasites during placenta and tissue invasion in mice; however, its effects on the behaviour of the animals are unknown. Thus, behavioural analysis was carried out in pregnant infected Swiss mice under BLLT (applied continuously for 12 hours, from 7 am to 7 pm, maintaining an intensity of 460 nm and 7 μW/cm²). Infected mice, regardless of light exposure, exhibited increased inactivity and reduced maintenance behaviours. BLLT influenced certain behaviours, such as an increase in abnormal behaviours in infected mice and higher food and water intake in non-infected mice, suggesting a potential stress effect. Grooming decreased under BLLT in infected mice, while affiliative interactions were reduced in non-infected mice under conventional light. Activity levels were largely unaffected in infected mice, but blue light exposure increased activity in non-infected mice. While our study highlights the potential of BLLT to reduce parasite load, further research is needed to investigate the long-term behavioural and physiological effects, as well as to clarify the mechanisms involved. In conclusion, BLLT may mitigate parasite load and influence behavioural outcomes, while prolonged exposure can act as a stressor, moderately affecting welfare. Future research should explore optimized light regimens, integrate physiological and behavioural measures, and evaluate long-term effects to balance therapeutic efficacy and animal welfare.
    DOI:  https://doi.org/10.1371/journal.pone.0353740
  7. Curr Opin Struct Biol. 2026 Jul 17. pii: S0959-440X(26)00118-1. [Epub ahead of print]100 103336
    Structural dissection of apicomplexan gliding motility.
    Pankti Vaishnav, Josie L Ferreira.
      Malaria, toxoplasmosis, and cryptosporidiosis are caused by apicomplexan parasites, which invade host cells through gliding motility. A fundamental paradox defines this system: how do parasites achieve efficient gliding using the most unstable actin filaments known in eukaryotes? Recent structural advances have begun to resolve this question by revealing spatial mechanisms that compensate for this instability. Cryo-electron microscopy demonstrated how divergent actin isoforms, specialised connectors, and conserved nucleation sites orchestrate a molecular conveyor belt operating with spatial control. Filaments are nucleated apically, channelled via gates, guided along defined tracks, and recycled posteriorly. This continuous and rapid turnover prevents actin accumulation while enabling efficient motility, critical for parasite transmission.
    DOI:  https://doi.org/10.1016/j.sbi.2026.103336
  8. Med Chem Res. 2026 Apr;35(4): 770-777
    Site-Specific incorporation of lysine acetyl-methylation into proteins.
    Jingxiang Zhao, Xinlong Guo, Xuelian Ren, Jiyang Yu, Xiaohan Song, He Huang.
      Lysine acetyl-methylation (Kam) is a novel protein post-translational modification (PTM) recently identified on histone H4, yet its biological functions on non-histone proteins remain largely unexplored. Here, we engineered an orthogonal Methanosarcina barkeri pyrrolysyl-tRNA synthetase (MbPylRS) variant and tRNACUAPyl pair for site-specific Kam incorporation into proteins in mammalian cells. Using this system, we identified endogenous Kam sites at K28 of adenylate kinase 2 (AK2) and K207 of pyruvate kinase M2 (PKM2) through proteomic analysis. Functional characterization revealed that Kam at these evolutionarily conserved residues significantly attenuated enzymatic activity. These findings demonstrate that Kam serves as a regulatory mechanism for non-histone proteins, and the ability to generate proteins harboring Kam at defined sites provides a valuable approach for investigating the biological roles of this newly identified PTM.
    Keywords:  Functional characterization; Genetic Code Expansion; Lysine acetyl-methylation; Post-translational modification; Site-specific incorporation
    DOI:  https://doi.org/10.1007/s00044-026-03544-3
  9. Cell Chem Biol. 2026 Jul 16. pii: S2451-9456(26)00233-3. [Epub ahead of print]33(7): 966-981
    The pyruvate dehydrogenase complex at the crossroads of cancer metabolism and cell death.
    Xiutao Cai, Fangquan Chen, Ruirui Liang, Hu Tang, Qile Zhou, Junhao Lin, Rui Kang, Daolin Tang, Jiao Liu.
      The pyruvate dehydrogenase complex (PDHC) is a key metabolic hub that couples glycolysis-derived carbon flux to the tricarboxylic acid cycle and mitochondrial function. Its activity is regulated by pyruvate dehydrogenase kinases, phosphatases, and lysine acylation, enabling dynamic responses to metabolic and stress signals. In cancer, dysregulation of the PDK-PDHC axis reduces PDH flux, promotes aerobic glycolysis, and enhances adaptation to mitochondrial and oxidative stress, thereby influencing susceptibility to regulated cell death. Recent studies further suggest that PDHC exhibits considerable structural and functional plasticity under hypoxia and redox stress. Growing preclinical and translational evidence indicates that targeting the PDK-PDHC axis may redirect metabolic flux and improve therapeutic responses in selected tumor contexts. This review summarizes current understanding of PDHC regulation, its context-dependent roles in regulated cell death, and the therapeutic potential and challenges of exploiting PDH-related metabolic vulnerabilities in cancer.
    DOI:  https://doi.org/10.1016/j.chembiol.2026.06.009
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