bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2026–05–10
eleven papers selected by
Lakesh Kumar, BITS Pilani
  1. Evolutionary remodeling of ubiquinone biosynthesis in Toxoplasma gondii reveals an essential bi-functional monooxygenase.
  2. Organization of Myosin H in the Apical Complex of Toxoplasma Gondii Revealed by 3D Single-Molecule Super-Resolution Microscopy.
  3. Cysteine cathepsin proteases in apicomplexan parasites.
  4. Toxoplasma gondii GRA12 Inhibits the NF-ΚB Signaling Pathway by Targeting P65 and the IKK Complex.
  5. Toxoplasma gondii hijacks host S100A6 to enhance cell migration and brain cyst formation.
  6. Lipidomic Profiling of Colonic Contents in Mice with Acute Toxoplasma gondii Infection.
  7. A New Conditional Transcription Factor for Use in Toxoplasma Gondii.
  8. Toxoplasma GRA72 is Involved in Membrane-Associated Functions and Metabolic Homeostasis Revealed by Transcriptomic Analysis.
  9. Host-cell dependent epigenetic profiles associated with survival outcomes in T. gondii infection.
  10. Toxoplasma gondii and a Cancer Biology Dichotomy: A Systematic Review of Experimental Studies of Its Antitumor and Pro-Tumor Effects.
  11. Live attenuated RHΔtkl1 and PruΔpp2a-c mutants of Toxoplasma gondii are promising vaccine candidates conferring protection in pigs.
  1. Nat Commun. 2026 May 07.
    Evolutionary remodeling of ubiquinone biosynthesis in Toxoplasma gondii reveals an essential bi-functional monooxygenase.
    Baihetiya Baierna, Taufiq Rahman, Scott Latimer, Gilles J Basset, Silvia N J Moreno.
      Apicomplexan parasites like Toxoplasma gondii harbor a divergent mitochondrial proteome, much of which remains uncharacterized despite its essentiality for parasite survival. One such essential pathway is ubiquinone (UQ) biosynthesis. Here, we characterize the UQ synthesis machinery in T. gondii and show that conserved enzymes, TgCoq3 and TgCoq5, are essential for growth and mitochondrial function, and associate in a multi-protein complex. Using proximity labeling and subcellular fractionation, approaches suited to detect low-abundance proteins, we identify TgCoqFMO, a FAD-dependent monooxygenase required for UQ synthesis. Unlike canonical eukaryotic systems that employ multiple monooxygenases to modify specific carbons on the UQ aromatic ring, TgCoqFMO catalyzes two distinct hydroxylation steps, an activity not previously reported in eukaryotes. Molecular docking and chemical screening identified TgCoqFMO inhibitors that impair tachyzoite growth and reduce bradyzoite viability. These findings reveal a divergent UQ biosynthesis pathway with fewer components in apicomplexans and establish TgCoqFMO as a promising antiparasitic target.
    DOI:  https://doi.org/10.1038/s41467-026-71902-1
  2. bioRxiv. 2026 Apr 27. pii: 2026.04.23.720434. [Epub ahead of print]
    Organization of Myosin H in the Apical Complex of Toxoplasma Gondii Revealed by 3D Single-Molecule Super-Resolution Microscopy.
    Ashwin Balaji, Li-Av Segev Zarko, Andrew E S Barentine, John C Boothroyd, W E Moerner.
      Toxoplasma gondii is a single-celled eukaryotic parasite with prolific invasion capability. The parasite uses an apical complex comprised of proteinaceous structures and secretory organelles to efficiently enter host cells. As a result, the apical complex remains a vital structure of interest, with many studies dedicated to understanding its protein organization. One such protein is the motor Myosin H (MyoH), which is indispensable for parasite motility and host cell invasion. Given the small size of the complex, roughly a diffraction-limited volume in the visible, high-resolution techniques are required to make precise determinations of protein organization. In this work, we use 3D single-molecule localization microscopy in both traditionally fixed and gel-expanded parasites to localize the indispensable motor Myosin H within the apical complex. Labeling of the N- and C-terminus of MyoH in fixed parasites resolved the orientation of the motor protein in the apical complex, showing the motor head radially exterior to the tail. Two-color imaging of MyoH with tubulin in fixed parasites allowed for localization of the MyoH termini relative to the conoid, a barrel of tubulin-based fibers in the apical complex and showed the MyoH tail toward the interior face of the conoid and the head at the conoid exterior. Gel expansion showed improved labeling density for both tubulin and MyoH but altered MyoH localization, highlighting the nuanced effects of gel expansion on protein organization.
    Statement of Significance: This work employs 3D single-molecule super-resolution microscopy to provide quantitative physical analysis of the spatial organization of a vital myosin motor, MyoH, in the model apicomplexan parasite Toxoplasma gondii . While previous studies have provided high-resolution views of the parasite's invasion machinery, MyoH has remained elusive at the nanoscale. We resolved differences in radial organization between the N- and C-termini of the motor, thus determining the orientation of the protein in the apical space. Two-color imaging revealed the organization of the motor in the greater context of the parasite's invasion complex. 3D single-molecule imaging in gel-expanded samples revealed an increase in labeling efficiency but perturbed localization of only the MyoH C-terminus, highlighting the nuanced effects of gel expansion on protein organization.
    DOI:  https://doi.org/10.64898/2026.04.23.720434
  3. Biol Chem. 2026 May 07.
    Cysteine cathepsin proteases in apicomplexan parasites.
    Antoine Mayté, Anne Silvestre, Florian Veillard, Sonia Lacroix-Lamandé, Gilles Lalmanach, Julie Tottey.
      Cysteine cathepsins are papain-like proteases which play key roles in a large range of organisms, including apicomplexan parasites. These obligate endoparasites are responsible for many devastating diseases in human and/or animal hosts, for which available treatments are limited or face the emergence of resistance. This review presents the cysteine cathepsins expressed by five major Apicomplexa (Plasmodium falciparum, Cryptosporidium parvum, Toxoplasma gondii, Eimeria tenella and Babesia bovis), highlighting available data on their structures, specific or common features, and biological functions in the parasite biology and host-parasite interactions. Although they belong to the same phylum, apicomplexan parasites have very distinct life cycles and biology, which are well adapted to the hosts they infect and to the tissues within which they develop. Accordingly, apicomplexan cysteine cathepsins display a wide variety of functions, associated with shared (e.g., invasion of and egress from host cells) or unique (e.g., degradation of haemoglobin in P. falciparum) biological pathways. Through their crucial functions and involvement in multiple parasite stages, these parasitic proteases represent assumed therapeutic targets. The description of apicomplexan cysteine cathepsins also appears uneven within the phylum, and further exploration of their biology and role is needed to drive novel preventive or curative intervention strategies.
    Keywords:  apicomplexa; cathepsin inhibitors; cysteine cathepsins; host-parasite interactions; parasites
    DOI:  https://doi.org/10.1515/hsz-2025-0240
  4. Genes (Basel). 2026 Apr 17. pii: 476. [Epub ahead of print]17(4):
    Toxoplasma gondii GRA12 Inhibits the NF-ΚB Signaling Pathway by Targeting P65 and the IKK Complex.
    Meiling Ou, Xiaowen Fang, Ying Yuan, Zhizhuo Huang, Boren Bai, Xiuying Hou, Yongjun Li, Chunxia Jing, Guang Yang.
       BACKGROUND: The NF-κB signaling pathway plays a critical role in innate immune defense against infections. However, many pathogens secrete toxins or effectors into host cells to manipulate cellular functions for their survival and proliferation. Toxoplasma gondii is known to establish chronic infections by employing sophisticated immune evasion strategies. Dense granule (GRA) proteins are essential for the survival and pathogenesis of T. gondii.
    METHODS: In this study, plasmid transfection, cell culture, luciferase reporter assay, quantitative PCR, and western blot were employed to identify T. gondii GRA proteins that regulate the NF-κB pathway.
    RESULTS: We demonstrate that GRA12, a specific GRA protein, significantly inhibits NF-κB promoter activity and the transcriptional expression of key cytokines, including IL-6, IL-12, TNF-α, and IFN-β. Western blot analysis further revealed that GRA12 suppresses the activation of the IKK complex and p65. Moreover, GRA12 prevents the nuclear translocation of p65.
    CONCLUSIONS: Our findings demonstrate that GRA12 is involved in immune evasion by inhibiting the NF-κB pathway, thereby facilitating T. gondii dissemination and infection.
    Keywords:  GRA12; NF-κB signaling pathway; Toxoplasma gondii; dense granule protein
    DOI:  https://doi.org/10.3390/genes17040476
  5. Commun Biol. 2026 May 05.
    Toxoplasma gondii hijacks host S100A6 to enhance cell migration and brain cyst formation.
    Lijuan Zhou, Weihao Zou, Shuyu Zheng, Zixuan Xin, Jiao Peng, Min Chen, Chi Zhang, Zihan Yang, Hongjuan Peng.
      Toxoplasma gondii (T. gondii) has the ability to disseminate widely in the host, including crossing the blood brain barrier (BBB) to establish persistent brain cysts. However, the molecular mechanism by which T. gondii hijacks host immune cell migration to facilitate its own dissemination remain incompletely understood. Here we show that T. gondii infection upregulates S100A6 via a calcium and P65-dependent pathway; This elevated S100A6 expression promoted its interaction with filamin A, leading to promoted cytoskeletal reorganization, enhanced cell migration and T. gondii replication. Furthermore, S100A6 knockout in C57BL/6 J mice decreases BBB permeability, inhibits tachyzoite traversal into the brain, and results in fewer and smaller brain cysts. These findings identify S100A6 as a critical regulator of T. gondii induced cell migration and dissemination, and suggest that targeting S100A6 or its downstream signaling can offer therapeutic strategies to limit parasite spread and prevent chronic neuro-toxoplasmosis.
    DOI:  https://doi.org/10.1038/s42003-026-10155-6
  6. Microorganisms. 2026 Apr 03. pii: 824. [Epub ahead of print]14(4):
    Lipidomic Profiling of Colonic Contents in Mice with Acute Toxoplasma gondii Infection.
    Cai-Qin Deng, Wen-Jie Cheng, Yuan-Lan Wang, Yi-Dan Wang, Feng-Cai Zou, Xing-Quan Zhu, Zhao Li.
       BACKGROUND: While Toxoplasma gondii infection poses a significant health threat, its impact on the localized intestinal lipid metabolism remains unclear.
    METHODS: Thus, this study established an acute infection model in BALB/cJ mice and analyzed the colonic contents collected 10 days post-infection via untargeted lipidomics. The lipid profiles of the two groups diverged substantially, with a clear separation evident between infection and control conditions.
    RESULTS: We identified 65 upregulated and 87 downregulated differential lipids, primarily falling into the glycerophospholipids and sphingolipids categories. Pathway enrichment analysis revealed that the choline metabolism in cancer and glycerophospholipid metabolism pathways was pinpointed as being among the most perturbed following infection. Correlation and network analyses further suggested that key molecules, such as LPC (20:4) and LPA (18:0), may mediate these metabolic pathway abnormalities by regulating related enzymatic activities.
    CONCLUSIONS: This systematic characterization of the intestinal lipid metabolic landscape in mice during acute T. gondii infection revealed the host intestinal lipid metabolic reprogramming induced by T. gondii infection. The findings offer a novel metabolic perspective for understanding T. gondii pathogenesis and host-parasite interactions.
    Keywords:  Toxoplasma gondii; acute infection; colonic contents; lipidomics
    DOI:  https://doi.org/10.3390/microorganisms14040824
  7. Biotechnol J. 2026 May;21(5): e70240
    A New Conditional Transcription Factor for Use in Toxoplasma Gondii.
    Mohammad Farouq Sharifpour, Shadi Khadiv, Alessandro D Uboldi, Amalie A Jayawickrama, Sarah Manning, Jonathan Whittall, Cynthia D K Bottema, John T Ellis, Daniel K Howe, Danny W Wilson, Farhid Hemmatzadeh, Christopher J Tonkin, Milton M McAllister.
      Toxoplasma gondii is an intracellular eukaryotic parasite in the phylum Apicomplexa. Reversible, conditional control of gene transcription was achieved previously in this organism using a tet-off system that was controlled by tetracycline. Although revolutionary for the field at the time, that system in Toxoplasma yielded modest signal-to-noise ratios (SNR) and proved to be leaky in the "off" state (i.e., it suffered from high background expression). Here we report the development of a new reversible and robust Conditional Transcription Factor (CTF) that is controlled by rapamycin. Although we originally intended to design a dimerizable drug-on transcription control system, the CTF unexpectedly functions in a drug-off fashion. In stably-transfected tachyzoites, CTF regulates a fluorescent reporter gene in Toxoplasma to achieve almost no background expression in the presence of rapamycin (i.e. near-zero leakiness), while in the absence of rapamycin 84% of tachyzoites express EYFP in comparison with 87% of constitutively-expressed positive controls, with 59% mean fluorescence intensity relative to positive controls. Conditional regulation of the median fluorescence intensity of the reporter gene reached an impressive SNR averaging 1489, approximating an "on/off" switch. The modular design of the CTF is expected to facilitate application to varied genes, incremental modifications, and adaptation for use in other apicomplexan organisms.
    Keywords:  FKBP; apicomplexa; artificial transcription factor; conditional gene expression; gene regulation; rapamycin; signal‐to‐noise ratio
    DOI:  https://doi.org/10.1002/biot.70240
  8. Acta Parasitol. 2026 May 02. pii: 100. [Epub ahead of print]71(3):
    Toxoplasma GRA72 is Involved in Membrane-Associated Functions and Metabolic Homeostasis Revealed by Transcriptomic Analysis.
    Xin-Sheng Lu, Xing Tian, Jing Li, Chen-Ran Tian, Xing-Quan Zhu, Xiao-Nan Zheng.
      
    Keywords:   Toxoplasma gondii ; GO; GRA72; KEGG; Transcriptomics
    DOI:  https://doi.org/10.1007/s11686-025-01190-0
  9. Epigenetics Chromatin. 2026 May 05.
    Host-cell dependent epigenetic profiles associated with survival outcomes in T. gondii infection.
    Loic Ciampossin, Arzu Ulu, Todd Lenz, Zehao Li, Steven Abel, Sandeep Srivastava, Michael White, Emma Wilson, Karine G Le Roch.
      Toxoplasmosis is a widespread parasitic disease affecting roughly one-third of the global population. In immunocompromised individuals or during pregnancy, infection can result in severe complications. Following primary infection, Toxoplasma gondii forms dormant bradyzoite cysts in tissues such as the brain and eyes. These cysts can rupture, particularly in immunocompromised hosts, releasing active parasites and triggering recrudescence. Efforts to experimentally induce and study bradyzoite cyst recrudescence have been hindered by the limited capacity of cell culture adapted strains to form tissue cysts in vivo. T. gondii employs diverse strategies to persist within host cells, including manipulation of host metabolism and immune responses, and these strategies may vary by host cell type. Here, we profiled epigenomic and transcriptomic features associated with differential parasite survival in distinct cell types. Using an ex vivo model of the Type II ME49 strain unadapted to fibroblast culture, we compared parasite survival and epigenetic profiles in neonatal mouse astrocytes (AST) and human foreskin fibroblasts (HFF). Comparative analyses revealed marked divergence in parasite population dynamics, accompanied by reduced H3K4me3 enrichment at promoter regions in parasites grown in HFF. This epigenetic shift correlated with transcriptomic changes in genes linked to cell cycle progression, growth, and development, including a subset of AP2 transcription factors, underscoring the influence of host cell type on parasite biology.
    DOI:  https://doi.org/10.1186/s13072-026-00678-x
  10. Pathogens. 2026 Mar 26. pii: 351. [Epub ahead of print]15(4):
    Toxoplasma gondii and a Cancer Biology Dichotomy: A Systematic Review of Experimental Studies of Its Antitumor and Pro-Tumor Effects.
    Saachi Jhandi, Brenda Anissa Vera, Julian Galindo, Jose G Montoya, Despina G Contopoulos-Ioannidis.
      Toxoplasma gondii (T. gondii) is an intracellular parasite known to modulate host immunity and cellular signaling, raising interest in its potential influence on cancer biology. A systematic review was conducted to evaluate experimental evidence on the antitumor or pro-tumor effects of T. gondii infection and parasite-derived antigens and to categorize the underlying mechanisms. PubMed was searched through 9 September 2024, and 54 eligible experimental studies were included (41 in vivo, 10 in vitro, and three combined). Forty-six studies reported antitumor effects, two pro-tumor effects, one stage-dependent divergent effects (acute infection/antitumor vs. chronic infection/pro-tumor), and five highlighted T. gondii-associated cancer-pertinent signaling pathways. Antitumor effects were observed following acute infection and exposure to parasite antigens, certain recombinant proteins, and exosomal microRNA miR-155-5p. Dominant mechanistic categories included activation of innate and adaptive immunity and reversal of tumor microenvironment immunosuppression (notably Th1-driven IL-12/IFN-γ responses, antitumor M1 macrophage polarization), induction of apoptosis, anti-angiogenesis, molecular mimicry and modulation of cancer-pertinent pathways. Conversely, pro-tumor effects were seen with chronic infection and exposure to ROP18 effector protein and miR-21. Future translational research should focus on rigorous evaluation of the safety and efficacy of attenuated non-replicating T. gondii strains and/or select recombinant antigens for potential cancer T. gondii-based immunotherapy.
    Keywords:  T. gondii; Toxoplasma gondii; acute infection; antitumor; cancer biology; cancer immunotherapy; chronic infection; experimental studies; in vitro; in vivo; parasite antigens; pro-tumor; protumor; recombinant antigens; systematic review; translational research
    DOI:  https://doi.org/10.3390/pathogens15040351
  11. Infect Dis Poverty. 2026 May 06. pii: 49. [Epub ahead of print]15(1):
    Live attenuated RHΔtkl1 and PruΔpp2a-c mutants of Toxoplasma gondii are promising vaccine candidates conferring protection in pigs.
    Ze-Xuan Wu, Yu Kang, Zhi Zheng, Wen-Bo Hao, Shi-Bo Huang, Yu-Xuan Wang, Xiao-Nan Zheng, Xing-Quan Zhu.
       BACKGROUND: Toxoplasma gondii is an apicomplexan parasite which infects nearly all warm-blooded animals and humans, causing zoonotic toxoplasmosis. Pork infected with T. gondii is considered a significant source of human infection. Currently, no commercial vaccines are available for porcine toxoplasmosis globally, thus a safe and effective vaccine is urgently needed. This study evaluated the immuno-protective effects of two T. gondii gene knockout attenuated strains, RHΔtkl1 and PruΔpp2a-c, in pigs.
    METHODS: Pigs immunized by intramuscular injection with 1 × 107 tachyzoites of attenuated RHΔtkl1 or PruΔpp2a-c strains were challenged orally with 1.000 sporulated oocysts of the Pru strain at 28 days post-vaccination (dpv), followed by a secondary challenge via intraperitoneal injection of 1 × 107 Pru strain tachyzoites at 70 dpv. Clinical signs were monitored. T. gondii-specific antibody levels were examined by enzyme-linked immunosorbent assay. The protective efficacy was evaluated by analyzing pathological lesions, pathological score, parasite load, brain cyst burden, and by mouse bioassay. GraphPad Prism software was employed to perform the log-rank (Mantel Cox) test, Student's t test and one-way ANOVA.
    RESULTS: Pigs immunized with either RHΔtkl1 or PruΔpp2a-c exhibited only low-grade fever. Combined with pathological changes and pathological scores, these findings support the moderate safety of both strains. Pigs immunized with either RHΔtkl1 or PruΔpp2a-c and subsequently challenged with T. gondii Pru oocysts and tachyzoites exhibited a sharp increase in T. gondii-specific antibodies, which remained high for 5 weeks (P < 0.01). Pathological lesions were alleviated after immunization, with a significant reduction in parasite load observed in tissues including the brain, heart, gastrocnemius, longissimus dorsi, psoas major, and diaphragm (P < 0.01). Furthermore, a marked decrease in brain cyst burden was recorded (P < 0.0001). Mouse bioassay results confirmed a significant reduction in the proportion of mouse brain tissues positive for T. gondii genomic DNA in the group immunized and then challenged, compared to the non-immunized challenged group (P < 0.0001).
    CONCLUSIONS: The two live attenuated RHΔtkl1 and PruΔpp2a-c mutants of demonstrated moderate safety, immunogenicity, and protective efficacy in pigs, identifying them as potential candidate vaccines against porcine toxoplasmosis.
    Keywords:   Toxoplasma gondii ; Immunization; Live attenuated vaccine; Pig; RHΔtkl1 and PruΔpp2a-c mutants
    DOI:  https://doi.org/10.1186/s40249-026-01451-8
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