bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2026–01–25
twelve papers selected by
Lakesh Kumar, BITS Pilani
  1. Editorial: Molecular mechanisms of the host immune response to Toxoplasma gondii infection.
  2. Unraveling the role of host kinase PIM1 in Toxoplasma gondii infection: Implications for therapies.
  3. Toxoplasma gondii-induced region-specific disintegration in glutamatergic neurotransmission is linked to cognitive impairments in mice.
  4. Global Profiling of Lysine Succinylation Reveals Acetylation Crosstalk Underlying Metabolic Regulation in Chlamydomonas reinhardtii.
  5. Linking cellular metabolism to chromatin modifications in plants.
  6. Genome-wide identification and multi-dimensional functional characterization of the SIR2 family in Brassica napus L.
  7. Acetylation dynamics of MrATG4 governing autophagy-mediated conidiation in an entomopathogenic fungus.
  8. Histone and non-histone (de)acetylation impact on the blood-brain barrier.
  9. Insect Lipidomics: Advances, Applications, and Physiological Insights.
  10. Transcriptional Control of Lipid Metabolism.
  11. Erratum for Moss et al., "Apicomplexan phosphodiesterases in cyclic nucleotide turnover: conservation, function, and therapeutic potential".
  12. Positive feedback regulation between USP8 and Hippo/YAP axis drives triple-negative breast cancer progression.
  1. Front Immunol. 2025 ;16 1754559
    Editorial: Molecular mechanisms of the host immune response to Toxoplasma gondii infection.
    Jing Yang, Rui Fang.
      
    Keywords:  GBPs (guanylate-binding proteins); IFNs (interferons); IRGs (immunity-related GTPases); P2X7R; Toxoplasma gondii; dual single-cell sequencing; ocular toxoplasmosis; scDual-Seq
    DOI:  https://doi.org/10.3389/fimmu.2025.1754559
  2. PLoS Negl Trop Dis. 2026 Jan 20. 20(1): e0013915
    Unraveling the role of host kinase PIM1 in Toxoplasma gondii infection: Implications for therapies.
    Lijie Pan, Fan Zhang, Yun Yang, Yue Sun, Lingling Song, Famin Zhang, Jinjin Zhu, Yang Wang, Chong Wang, Qingli Luo, Wen Zhang, Li Yu, Yuanyuan Cao.
      Toxoplasma gondii, a widespread intracellular protozoan parasite, infects a significant portion of the global human population. Restricted to an acute-infection model, this study elucidates the role of the host protein PIM1, a serine/threonine protein kinase, in facilitating T. gondii proliferation and its potential as a therapeutic target. Employing both in vitro and in vivo models, we establish that PIM1 enhances the intracellular proliferation of T. gondii by suppressing host cell apoptosis. Our findings underscore the necessity of PIM1's kinase activity in this process, as evidenced by the significant reduction in T. gondii proliferation upon treatment with either a kinase-dead PIM1 mutant or the PIM1 inhibitor AZD1208. In murine models, AZD1208 treatment resulted in decreased T. gondii load and elevated pro-apoptotic markers in tissues, indicating that PIM1 inhibition bolsters the host's immune response against the parasite. Since the role of PIM1 in chronic infection remains unexplored, follow-up studies using chronic models are essential. Collectively, our findings illuminate host-parasite interplay during acute toxoplasmosis and position PIM1 as a promising target for anti-T. gondii therapeutics.
    DOI:  https://doi.org/10.1371/journal.pntd.0013915
  3. iScience. 2026 Jan 16. 29(1): 114415
    Toxoplasma gondii-induced region-specific disintegration in glutamatergic neurotransmission is linked to cognitive impairments in mice.
    Iurii Savaateev, Lorena Morton, Henning Peter Düsedau, Johannes Steffen, Sanja Mikulovic, Dirk Montag, Björn H Schott, Ildiko Rita Dunay.
      Chronic infection with the protozoan parasite Toxoplasma gondii (T. gondii) elicits distinct alterations in both the immune and nervous system of the host. Previous studies correlated the persistent neuroinflammatory response triggered by chronic T. gondii infection to specific behavioral alterations. Here, we causally link chronic cerebral T. gondii infection to cognitive and motor impairments in mice, as well as to the altered brain glutamatergic signaling in hippocampus, striatum, and cortex. By combining synaptic composition analysis assessed via flow synaptometry with the standard sulfadiazine treatment, we demonstrated the regional specificity of the detected alterations of cerebral T. gondii infection. Importantly, our behavioral analysis exposed the restoration of behavioral flexibility in shifting between goal-directed and habitual action control, with more motorically demanding skills such as social novelty recognition and locomotion being only partially restored. We argue that the revealed regional effects of both T. gondii and sulfadiazine treatment may be a key factor accounting for treatment-resistant behavioral traits.
    Keywords:  Cognitive neuroscience; Immunology; Neuroscience; Parasitology
    DOI:  https://doi.org/10.1016/j.isci.2025.114415
  4. J Agric Food Chem. 2026 Jan 20.
    Global Profiling of Lysine Succinylation Reveals Acetylation Crosstalk Underlying Metabolic Regulation in Chlamydomonas reinhardtii.
    Shengchao Yu, Xiaoyun Liu, Aijie Tian, Ying Zhang, Zhiying Yue, Zhangfeng Hu.
      Lysine succinylation is an evolutionarily conserved post-translational modification (PTM) involved in cellular metabolic regulation. Chlamydomonas reinhardtii, a GRAS-certified microalga and emerging chassis for biofuel and biobased production, has not yet been systematically characterized for succinylation. Here, we present a comprehensive proteome-wide lysine succinylome map of Chlamydomonas and identify 2806 high-confidence succinylation sites across 791 proteins. These proteins were predominantly distributed in chloroplasts, cytoplasm, and mitochondria and were significantly enriched in pathways central to carbon and lipid metabolism. Comparative analyses revealed extensive crosstalk between succinylation and acetylation with distinct sequence patterns and functional preferences. Site-directed mutagenesis and enzymatic assays revealed that succinylation at K597 of Acetyl-CoA synthetase 3 (ACS3) markedly reduced enzymatic activity, with an inhibitory effect stronger than that of acetylation. These findings establish succinylation as a key metabolic regulator and provide a valuable resource for advancing metabolic engineering in algae.
    Keywords:  Chlamydomonas reinhardtii; acetyl-CoA synthetase; acylation crosstalk; lysine succinylation; metabolic regulation
    DOI:  https://doi.org/10.1021/acs.jafc.5c12224
  5. J Integr Plant Biol. 2026 Jan 21.
    Linking cellular metabolism to chromatin modifications in plants.
    Jaewoong Hwang, Pil Joon Seo.
      Beyond their traditional roles as biological building blocks and energy sources, metabolites also influence gene expression, exerting direct effects on the epigenetic landscape. For example, core metabolites such as acetyl coenzyme A (acetyl-CoA) and S-adenosylmethionine (SAM) serve as substrates or cofactors for chromatin-modifying enzymes, thereby modulating transcription through the chemical modification of histones and DNA. In addition, metabolites regulate the transcription of the genes encoding these chromatin modifiers, as well as the post-translational modifications and enzymatic activities of these proteins. Therefore, we propose that the metabolic state of a cell or organism is a dynamic and active driver of epigenomic reprogramming, adjusting gene expression in response to fluctuations in the environment.
    Keywords:  DNA methylation; allosteric control; chromatin modifier; enzyme substrate; epigenetics; histone PTMs; metabolism
    DOI:  https://doi.org/10.1111/jipb.70150
  6. PLoS One. 2026 ;21(1): e0340688
    Genome-wide identification and multi-dimensional functional characterization of the SIR2 family in Brassica napus L.
    Hanbing Hu, Ling He, Rui Chen, Ziheng Jing, Heping Wan, Zilan Xiao, Hongtao Cheng, Chunhong Wu, Xiaoyun Liu.
      Silent Information Regulator 2 (SIR2) family proteins are NAD+-dependent histone deacetylases that play key roles in epigenetic regulation, plant development, and stress responses; however, systematic characterization of this family (hereafter SRTs) in the important oilseed crop Brassica napus (rapeseed) remains limited. In this study, we identified 4 SRT genes in the rapeseed genome, designated BnaASRT1/2 and BnaCSRT1/2, based on their homology to Arabidopsis SRTs and chromosomal localization. These genes encode proteins with conserved SIR2 domains, sharing >80% sequence identity and >95% coverage with Arabidopsis SRTs, and exhibit similar subcellular localizations (SRT1s in the nucleus, SRT2s in mitochondria). Phylogenetic and synteny analyses confirmed the evolutionary conservation of rapeseed SRTs, which originated from whole-genome duplication events and were stably inherited from its diploid ancestors (Brassica rapa and Brassica oleracea). Structural analysis indicates that gene structure, motifs, and promoter elements related to stress and hormone responses are conserved, although subtle differences in the promoters suggest functional specialization. Notably, GO enrichment and molecular docking assays demonstrated that BnaSRTs possess histone deacetylase activity, with strong binding affinity to key acetylation sites (e.g., H3K9ac). Treatment with the SIRT-specific inhibitor nicotinamide (NAM) significantly elevated histone acetylation levels and altered the expression of genes involved in photosynthesis, metabolism, and stress responses-further supporting BnaSRTs' ole in epigenetic regulation. Furthermore, expression profiling via the BnIR database showed tissue-specific expression of BnaSRTs (e.g., high BnaASRT2 expression in buds, flowers, and siliques) and dynamic responses to abiotic stresses (salt, drought, cold) and hormones (ABA, JA, IAA), with BnaSRT2s showing the most prominent expression changes. Collectively, these findings clarify the evolutionary conservation, structural features, and functional roles of the SIR2 family in rapeseed, laying a foundation for epigenetic improvement of its agronomic traits.
    DOI:  https://doi.org/10.1371/journal.pone.0340688
  7. PLoS Pathog. 2026 Jan 20. 22(1): e1013883
    Acetylation dynamics of MrATG4 governing autophagy-mediated conidiation in an entomopathogenic fungus.
    Deshui Yu, Yulong Wang, Rui Xie, Rong Zhou, Zhenbang Liu, Najie Shi, Xiangyun Xie, Yang Yang, Jiaojiao Qu, Guang Yang, Bo Huang.
      Conidial production is a critical factor determining the efficacy of entomopathogenic fungi as biocontrol agents. Autophagy, a fundamental cellular degradation process, plays an essential role in regulating fungal conidiation. However, the modulation of autophagy through acetylation, particularly concerning the autophagy-related protein ATG4, remains poorly understood in fungi. Here, we investigate the roles of the deacetylase MrSIR2-3 and the acetyltransferase MrKAT1 in Metarhizium robertsii, focusing on their impacts on autophagy and conidiation. Our findings demonstrate that deletion of MrSIR2-3 (ΔMrsir2-3) leads to elevated autophagy levels, whereas loss of MrKAT1 (ΔMrkat1) suppresses autophagy initiation; both alterations consequently impair conidiation. Interaction assays further reveal that the key autophagy factor MrATG4 is regulated by opposing acetylation and deacetylation mediated by MrKAT1 and MrSIR2-3, potentially via modification of lysine residues K69 and/or K77. This dynamic acetylation balance is essential for maintaining autophagy homeostasis and ensuring efficient conidiation. Collectively, our results provide novel insights into how the acetylation of ATG4 modulates autophagy, advancing our understanding of conidiation regulation in entomopathogenic fungi and highlighting potential targets for enhancing fungal biocontrol efficacy.
    DOI:  https://doi.org/10.1371/journal.ppat.1013883
  8. Fluids Barriers CNS. 2026 Jan 21. 23(1): 13
    Histone and non-histone (de)acetylation impact on the blood-brain barrier.
    Mariana Melo, Ana Fortuna, João Laranjinha, Joana Bicker.
      
    Keywords:  Blood-brain barrier; Epigenetics; Histone acetylase activators; Histone acetylases; Histone deacetylase inhibitors; Histone deacetylases
    DOI:  https://doi.org/10.1186/s12987-026-00763-z
  9. Adv Exp Med Biol. 2026 ;1494 261-291
    Insect Lipidomics: Advances, Applications, and Physiological Insights.
    Laura Palanker Musselman, Doga Cedden, Gözde Güney, Umut Toprak.
      Lipidomics, a specialized branch of metabolomics, investigates the diversity and functionality of lipids in biological systems. Lipids serve crucial roles in energy storage, membrane composition, and environmental acclimation in insects, underpinning processes such as development and stress responses. Advances in analytical technologies, such as liquid chromatography-mass spectrometry (LC-MS), have enabled precise identification and quantification of lipid species, providing unprecedented insights into lipid metabolism and dynamics. Key lipid classes, including triacylglycerols and phospholipids, exhibit structural and functional versatility, adapting to environmental pressures through mechanisms like homeoviscous adaptation. These dynamic lipid responses are essential for maintaining cellular and cuticular integrity and functionality under stress. By exploring lipid diversity and adaptations, lipidomics offers valuable perspectives on insect physiology, survival strategies, and evolutionary ecology. This chapter summarizes methods used to study insect lipidomes and highlights comparative lipidomic studies that have advanced our understanding of insect biology.
    Keywords:  Cuticular hydrocarbons; Diapause; Ecdysteroids; Insect lipidomics; Mass spectrometry
    DOI:  https://doi.org/10.1007/978-3-032-04842-4_878
  10. Adv Exp Med Biol. 2026 ;1494 163-200
    Transcriptional Control of Lipid Metabolism.
    Laura Palanker Musselman, Huy G Truong, Justin R DiAngelo.
      Transcriptional control of lipid metabolism uses a framework that parallels the control of lipid metabolism at the protein or enzyme level, via feedback and feed-forward mechanisms. Increasing the substrates for an enzyme often increases enzyme gene expression, for example. A paucity of product can likewise potentiate transcription or stability of the mRNA encoding the enzyme or enzymes needed to produce it. In addition, changes in second messengers or cellular energy charge can act as on/off switches for transcriptional regulators to control transcript (and protein) abundance. Insects use a wide range of DNA-binding transcription factors (TFs) that sense changes in the cell and its environment to produce the appropriate change in transcription at gene promoters. These TFs work together with histones, spliceosomes, and additional RNA processing factors to ultimately regulate lipid metabolism. In this chapter, we will first focus on the important TFs that control lipid metabolism in insects. Next, we will describe non-TF regulators of insect lipid metabolism such as enzymes that modify acetylation and methylation status, transcriptional coactivators, splicing factors, and microRNAs. To conclude, we consider future goals for studying the mechanisms underlying the control of lipid metabolism in insects.
    Keywords:  Insect; Lipid; Lipogenesis; Lipolysis; Metabolism; Splicing; Transcription factor; Transcriptional coactivator; Triglyceride; microRNA
    DOI:  https://doi.org/10.1007/978-3-032-04842-4_808
  11. mBio. 2026 Jan 21. e0000226
    Erratum for Moss et al., "Apicomplexan phosphodiesterases in cyclic nucleotide turnover: conservation, function, and therapeutic potential".
    William J Moss, Lorenzo Brusini, Ronja Kuehnel, Mathieu Brochet, Kevin M Brown.
      
    DOI:  https://doi.org/10.1128/mbio.00002-26
  12. Cell Death Dis. 2026 Jan 21.
    Positive feedback regulation between USP8 and Hippo/YAP axis drives triple-negative breast cancer progression.
    Xin Li, Penghe Yang, Tianshi Wang, Peng Su, Chenmiao Zhang, Shen Fangyu, Huijie Yang, Jian Zhu, Xiaodong Tan, Ting Zhuang.
      The hyper-activation of the Hippo/YAP axis was observed in triple-negative breast cancer (TNBC), which was crucial for tumor progression. The over-activation of YAP in TNBC remains unexplained, despite the continued functionality of the inhibitory phospho-cascade. Recently, studies revealed that the ubiquitin modifications of YAP also play important roles in the Hippo/YAP axis and cancer progression. In order to understand the potential mechanisms of ubiquitination and deubiquitination process in YAP function, we carried out siRNA screening for critical deubiquitinases in TNBC. Via the deubiquitinases (DUB) library, we identified Ubiquitin Specific Peptidase 8 (USP8) as an important effector in YAP function and TNBC progression. Inhibition of USP8 hampered TNBC progression via Hippo signaling. Clinical data revealed that USP8 expression correlated with YAP protein level and poor survival in TNBC patients. Biochemical evaluations revealed that USP8 has the ability to connect with YAP and suppress K48-linked polyubiquitination, thereby enhancing the stability of YAP. Interestingly, YAP directly binds to the USP8 promoter region, enhancing its transcription in TNBC. Our study revealed a forward feedback loop between USP8 and Hippo signaling in TNBC, indicating USP8 as a potential therapeutic drug targets in TNBC.
    DOI:  https://doi.org/10.1038/s41419-025-08356-8
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