bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2025–01–05
eleven papers selected by
Lakesh Kumar, BITS Pilani
  1. Erratum: Toxoplasma Gondii-Derived Exosomes: A Potential Immunostimulant and Delivery System for Tumor Immunotherapy Superior to Toxoplasma Gondii [Corrigendum].
  2. Association Between Toxoplasma gondii Infection and Serum Neurotransmitter Levels in Major Depressive Disorder Patients: A Case-Control Study in Bangladesh.
  3. A scaleable inducible knockout system for studying essential gene function in the malaria parasite.
  4. Targeting sirtuins in neurological disorders: A comprehensive review.
  5. Identification of Toxoplasma gondii in wild rodents in Poland by molecular and serological techniques.
  6. Genetic identification of acetyl-CoA synthetases involved in acetate activation in Haloferax mediterranei.
  7. Histone deacetylases synergistically regulate juvenile hormone signaling in the yellow fever mosquito, Aedes aegypti.
  8. Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress.
  9. H3K56 acetylation regulates chromatin maturation following DNA replication.
  10. Imaging malaria parasites across scales and time.
  11. The Warburg Effect: Is it Always an Enemy?
  1. Int J Nanomedicine. 2024 ;19 14019-14020
    Erratum: Toxoplasma Gondii-Derived Exosomes: A Potential Immunostimulant and Delivery System for Tumor Immunotherapy Superior to Toxoplasma Gondii [Corrigendum].
      [This corrects the article DOI: 10.2147/IJN.S483626.].
    DOI:  https://doi.org/10.2147/IJN.S513024
  2. J Parasitol Res. 2024 ;2024 7054920
    Association Between Toxoplasma gondii Infection and Serum Neurotransmitter Levels in Major Depressive Disorder Patients: A Case-Control Study in Bangladesh.
    Jerin E Gulshan, Samia Sultana Lira, M M A Shalahuddin Qusar, Md Ismail Hosen, Atiqur Rahman, Md Rabiul Islam, Taibur Rahman.
      Toxoplasma gondii (T. gondii) is an obligate, intracellular, neurotropic protozoan parasite. After primary infection, T. gondii parasite undergoes stage conversion from fast-replicating tachyzoites to slow-replicating dormant bradyzoites, particularly in the brain, and persists for a lifetime of an individual. In this study, the impact of T. gondii infection in individuals with psychological disorder, that is, major depressive disorder (MDD) has been studied. Ninety-five MDD (n = 95) patients were enrolled with age and sex-matched healthy controls (HCs, n = 90). The seroprevalence of T. gondii infection among these individuals was determined using the TOXO IgM/IgG Rapid Test Cassette that determines the anti-T. gondii IgM and IgG antibodies in the serum samples. Furthermore, to understand the impact of T. gondii in developing major depression, the serum level of neurotransmitters (i.e., dopamine, adrenaline, and noradrenaline) was determined using an enzyme-linked immunosorbent assay (ELISA). Our data suggest that anti-T. gondii IgG was slightly higher in MDD patients than in HCs. The level of dopamine was significantly lower in T. gondii-infected MDD patients than in HCs. However, adrenaline and noradrenaline levels showed increasing levels in T. gondii-infected MDD patients. The level of neurotransmitters was correlated with the DSM-D scores of MDD patients. These data, nevertheless, confirm that T. gondii might affect the level of neurotransmitters in MDD patients. However, whether the reduced level of dopamine and increased level of adrenaline and noradrenaline act as contributing factors for the development of MDD is yet to be known.
    Keywords:  Toxoplasma gondii; adrenaline; dopamine; major depression; noradrenaline
    DOI:  https://doi.org/10.1155/japr/7054920
  3. Nucleic Acids Res. 2024 Dec 31. pii: gkae1274. [Epub ahead of print]
    A scaleable inducible knockout system for studying essential gene function in the malaria parasite.
    Abhinay Ramaprasad, Michael J Blackman.
      The malaria parasite needs nearly half of its genes to propagate normally within red blood cells. Inducible ways to interfere with gene expression like the DiCre-lox system are necessary to study the function of these essential genes. However, existing DiCre-lox strategies are not well-suited to be deployed at scale to study several genes simultaneously. To overcome this, we have developed SHIFTiKO (frameshift-based trackable inducible knockout), a novel scaleable strategy that uses short, easy-to-construct, barcoded repair templates to insert loxP sites around short regions in target genes. Induced DiCre-mediated excision of the flanked region causes a frameshift mutation resulting in genetic ablation of gene function. Dual DNA barcodes inserted into each mutant enables verification of successful modification and induced excision at each locus and collective phenotyping of the mutants, not only across multiple replication cycles to assess growth fitness but also within a single cycle to identify specific phenotypic impairments. As a proof of concept, we have applied SHIFTiKO to screen the functions of malarial rhomboid proteases, successfully identifying their blood stage-specific essentiality. SHIFTiKO thus offers a powerful platform to conduct inducible phenotypic screens to study essential gene function at scale in the malaria parasite.
    DOI:  https://doi.org/10.1093/nar/gkae1274
  4. Int J Biol Macromol. 2024 Dec 28. pii: S0141-8130(24)10069-4. [Epub ahead of print]292 139258
    Targeting sirtuins in neurological disorders: A comprehensive review.
    Sen-Yu Zhang, Ni Yang, Peng-Hui Hao, Ri Wen, Tie-Ning Zhang.
      The sirtuin (SIRT) family is a group of seven conserved nicotinamide adenine dinucleotide-dependent histone deacetylases (SIRT1-SIRT7), which play crucial roles in various fundamental biological processes, including metabolism, aging, stress responses, inflammation, and cell survival. The role of SIRTs in neuro-pathophysiology has recently attracted significant attention. Notably, SIRT1-SIRT3 have been identified as key players in neuroprotection as they reduce neuroinflammation and regulate mitochondrial function. This review summarizes the latest research advancements in the role of the SIRT family in neurological diseases, mainly including neurodegenerative diseases, ischemia-related diseases, bleeding-related diseases, nervous system injury and other nervous system diseases, emphasizing their critical functions and associated signaling pathways, (e.g., AMPK/SIRT1/PGC-1α, AMPK/SIRT1/IL-1β/NF-κB, STAT2-SIRT4-mTOR, SIRT3/FOXO3α, and other signaling pathways in disease progression, particularly their protective roles in neurodegenerative diseases, ischemic injuries, and neural damage. Additionally, this review discusses progress in clinical studies targeting SIRT-specific small-molecule agonists and inhibitors. Further research on SIRTs may provide new insights into potential therapeutic strategies for the prevention and treatment of neurological disorders.
    Keywords:  Neurological disorders; Neuroprotection; Sirtuin
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139258
  5. Ann Agric Environ Med. 2024 Dec 22. pii: 184723. [Epub ahead of print]31(4): 626-630
    Identification of Toxoplasma gondii in wild rodents in Poland by molecular and serological techniques.
    Joanna Nowicka, Daniela Antolova, Anna Lass, Beata Biernat, Karolina Baranowicz, Aleksander Goll, Martyna Krupinska, Bartlomiej Ferra, Aneta Strachecka, Jerzy M Behnke, Anna Bajer, Maciej Grzybek.
      Rodents are recognized as reservoirs for Toxoplasma gondii, playing a crucial role in maintaining the parasite's presence in the environment. Biomonitoring was conducted to assess the role of sylvatic rodents in maintaining T. gondii, and to analyse the prevalence and seroprevalence of the parasite in seven wild rodent species. Rodents were collected in an open grassland study site located in northeastern Poland, and dissected. Brain, spleen, blood and serum samples were collected. Molecular (PCR assay, nested-PCR assay) and serological (ELISA and agglutination tests) methods were applied to indicate the best approach for application in the biomonitoring of T. gondii in small mammals. Samples were screened from 68 individuals using PCR assays but no T. gondii DNA were found. The agglutination test showed no signal. Antibodies against T. gondii were found in 5 sera samples out of 56 analysed (seroprevalence = 8.9% [4.4-16.8]). The results confirmed that rodents participate in the life cycle of T. gondii as reservoirs of this parasite in the sylvatic environment. However, for effective bio-monitoring of T. gondii in small mammals, the results suggest a preference for utilizing ELISA tests to detect T. gondii antigens, as opposed to relying solely on molecular methods.
    Keywords:  Toxoplasma gondii; biomonitoring; environment contamination; rodent-borne diseases; rodents; wildlife
    DOI:  https://doi.org/10.26444/aaem/184723
  6. Appl Environ Microbiol. 2024 Dec 31. e0184324
    Genetic identification of acetyl-CoA synthetases involved in acetate activation in Haloferax mediterranei.
    Ruchira Mitra, Yang Xu, Lin Lin, Jing Guo, Tong Xu, Mengkai Zhou, Feng Guo, Hao Li, Hua Xiang, Jing Han.
      Acetate/acetyl-CoA interconversion is an interesting metabolic node, primarily catalyzed by a set of various enzymes in prokaryotes. Haloferax mediterranei is a promising haloarchaeaon, capable of utilizing acetate as a sole carbon source for biosynthesis of high value-added products. Here, we have reported the key enzymes that catalyzed acetate activation in H. mediterranei. Based on bioinformatic and transcript analysis, thirteen possible candidate genes were screened. Simultaneous deletion of eleven genes led to a mutant strain (named as Δ11) that failed to grow on acetate. Gene complementation in Δ11 revealed six AMP-ACS (encoded by HFX_0870, HFX_1242, HFX_1451, HFX_6342, HFX_5131, and HFX_1643) and one ADP-ACS (encoded by HFX_0998) to be functional in acetate activation. Furthermore, heterologous expression of ADP-ACS genes from Haloarcula hispanica and Haloferax volcanii catalyzed acetate activation in Δ11. Subsequently, it was observed that, deletion of the six AMP-ACS genes in H. mediterranei ceased the cell growth of the resulting mutant (Δ6AMP-ACS) on acetate. An in vivo function of ADP-ACS in acetate activation could be excluded since ADP-ACS was downregulated on acetate. However, plasmid-based overexpression of ADP-ACS enabled Δ6AMP-ACS to grow on acetate, even better than the parent strain. Thus, it can be inferred that native ADP-ACS with low expression level was unable to mediate cell growth of Δ6AMP-ACS on acetate. This is the first genetic evidence exhibiting that overexpression of haloarchaeal ADP-ACS catalyzed acetate activation in vivo. Collectively, this is a comprehensive study of acetate activation in H. mediterranei, and the current findings would surely enrich the understanding of acetate metabolism in archaea.
    IMPORTANCE: Owing to the high demand and supply challenge of glucose, acetate might be considered a potential alternative carbon source for microbial growth and fermentation. Haloferax mediterranei is capable of utilizing acetate as a carbon source for growth and subsequent value-added product synthesis. Thus, it is essential to identify the genes responsible for acetate utilization in H. mediterranei. As per available literature, haloarchaeal ADP-forming acetyl-CoA synthetase (APD-ACS) catalyzes the reversible conversion of acetate to acetyl-CoA in vitro. However, in vivo, acetate activation and acetate formation are catalyzed by AMP-forming acetyl-CoA synthetase (AMP-ACS) and ADP-ACS, respectively. In this study, we have identified six AMP-ACS enzymes that catalyzed acetate activation in H. mediterranei. Deletion of these six genes abolished the growth of the resulting mutant (Δ6AMP-ACS) in acetate medium. The natively expressed ADP-ACS was unable to mediate its acetate activation in vivo. Interestingly, an artificial system based on plasmid overexpression of ADP-ACS in Δ6AMP-ACS restored its growth on acetate. This finding suggested that native ADP-ACS was unable to catalyze acetate activation in H. mediterranei due to its low expression level. Together, our study explored the acetate activation in H. mediterranei, and the obtained results would enrich the knowledge of acetate metabolism in archaea. Furthermore, the information offered in this study would benefit the improvement of acetate utilization in haloarchaea for value-added product synthesis.
    Keywords:  ADP-acetyl-CoA synthetase; AMP-acetyl-CoA synthetase; acetate activation; haloarchaea
    DOI:  https://doi.org/10.1128/aem.01843-24
  7. Insect Biochem Mol Biol. 2024 Dec 30. pii: S0965-1748(24)00187-5. [Epub ahead of print] 104256
    Histone deacetylases synergistically regulate juvenile hormone signaling in the yellow fever mosquito, Aedes aegypti.
    Sharath Chandra Gaddelapati, Subba Reddy Palli.
      Controlling Aedes aegypti mosquitoes is crucial for managing mosquito-transmitted diseases like dengue, zika, chikungunya, and yellow fever. One of the efficient methods to control mosquitoes is to block their progression from the larval to the adult stage. Juvenile hormones (JH) maintain the larval stage and ensure proper developmental timing for transitioning from larval-pupal-adult stages. Our previous studies showed that histone deacetylases (HDACs) regulate JH signaling and metamorphosis in the red flour beetle Tribolium castaneum. However, the role of HDACs in regulating JH signaling in Ae. aegypti mosquito is unknown. To investigate the role of HDACs in JH signaling, we knockdown each HDAC coding gene in Aag-2 cells derived from Ae. aegypti. Knockdown of HDAC1, HDAC4, and HDAC11 increased the expression of the JH primary response gene, Krüppel homolog 1 (Kr-h1), which represses the larval-pupal metamorphosis. Moreover, the simultaneous knockdown of these three HDACs synergistically increased the Kr-h1 promoter activity and its expression, mimicking JH action in inducing Kr-h1. Nevertheless, each HDAC regulates the transcription of different sets of genes, except for a few common genes involved in JH signaling. Furthermore, the knockdown of these HDACs in Ae. aegypti larvae caused different phenotypes apart from delayed pupation: HDAC1 knockdown caused larval growth retardation, body shrinkage, and eventual death; HDAC4 knockdown led to incomplete head capsule shedding after metamorphosis; and HDAC11 knockdown caused higher pupal mortality. Our data demonstrates functional overlap and distinct functions for HDAC1, HDAC4, and HDAC11 in modulating JH signaling, with each HDAC having a unique role in mosquito development.
    Keywords:  Epigenetics; HDAC; JH; Kr-h1; Metamorphosis
    DOI:  https://doi.org/10.1016/j.ibmb.2024.104256
  8. Transl Oncol. 2024 Dec 27. pii: S1936-5233(24)00385-1. [Epub ahead of print]52 102259
    Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress.
    Zejun Fang, Chaoju Gong, Yanyan Hu, Tingting Cui, Min Lin, Sha Lin, Ming Ye.
      E2F1 is a critical transcription factor that regulates cell cycle progression, is expressed at high levels in most cancer cells, and activates the biogenesis of proteins related to the cell cycle. Over recent years, researchers have demonstrated that E2F1 could also facilitate cellular apoptosis under conditions of cellular stress, thus creating a double-edged sword associated with both the regulation of cellular survival and death. However, the mechanisms responsible for these actions remain poorly understood. In this study, we demonstrated that serum stress could activate the acetylation of E2F1 at K125. Further analysis indicated that the acetylation of E2F1 at K125 could facilitate its interaction with the promoter of FAS and upregulate the levels of Fas. Furthermore, the acetylation of E2F1 attenuated its interaction with p53, thus leading to the transactivation of BAX. The upregulation of Fas and Bax activated the cleavage of caspase-3 and facilitated the apoptosis of HCC cells experiencing serum stress. Collectively, our findings indicated that the acetylation of E2F1 at K125 under serum stress leads to a functional change and a new role as an executor of cell death instead of an oncoprotein.
    Keywords:  Cell apoptosis; E2F1; HDAC5; Hepatocellular carcinoma; Serum stress
    DOI:  https://doi.org/10.1016/j.tranon.2024.102259
  9. Nat Commun. 2025 Jan 02. 16(1): 134
    H3K56 acetylation regulates chromatin maturation following DNA replication.
    Shoufu Duan, Ilana M Nodelman, Hui Zhou, Toshio Tsukiyama, Gregory D Bowman, Zhiguo Zhang.
      Following DNA replication, the newly reassembled chromatin is disorganized and must mature to its steady state to maintain both genome and epigenome integrity. However, the regulatory mechanisms governing this critical process remain poorly understood. Here, we show that histone H3K56 acetylation (H3K56ac), a mark on newly-synthesized H3, facilitates the remodeling of disorganized nucleosomes in nascent chromatin, and its removal at the subsequent G2/M phase of the cell cycle marks the completion of chromatin maturation. In vitro, H3K56ac enhances the activity of ISWI chromatin remodelers, including yeast ISW1 and its human equivalent SNF2h. In vivo, a deficiency of H3K56ac in nascent chromatin results in the formation of closely packed di-nucleosomes and/or tetra-nucleosomes. In contrast, abnormally high H3K56ac levels disrupt chromatin maturation, leading to genome instability. These findings establish a central role of H3K56ac in chromatin maturation and reveal a mechanism regulating this critical aspect of chromosome replication.
    DOI:  https://doi.org/10.1038/s41467-024-55144-7
  10. J Microsc. 2025 Jan 03.
    Imaging malaria parasites across scales and time.
    Julien Guizetti.
      The idea that disease is caused at the cellular level is so fundamental to us that we might forget the critical role microscopy played in generating and developing this insight. Visually identifying diseased or infected cells lays the foundation for any effort to curb human pathology. Since the discovery of the Plasmodium-infected red blood cells, which cause malaria, microscopy has undergone an impressive development now literally resolving individual molecules. This review explores the expansive field of light microscopy, focusing on its application to malaria research. Imaging technologies have transformed our understanding of biological systems, yet navigating the complex and ever-growing landscape of techniques can be daunting. This review offers a guide for researchers, especially those working on malaria, by providing historical context as well as practical advice on selecting the right imaging approach. The review advocates an integrated methodology that prioritises the research question while considering key factors like sample preparation, fluorophore choice, imaging modality, and data analysis. In addition to presenting seminal studies and innovative applications of microscopy, the review highlights a broad range of topics, from traditional techniques like white light microscopy to advanced methods such as superresolution microscopy and time-lapse imaging. It addresses the emerging challenges of microscopy, including phototoxicity and trade-offs in resolution and speed, and offers insights into future technologies that might impact malaria research. This review offers a mix of historical perspective, technological progress, and practical guidance that appeal to novice and advanced microscopists alike. It aims to inspire malaria researchers to explore imaging techniques that could enrich their studies, thus advancing the field through enhanced visual exploration of the parasite across scales and time.
    Keywords:  Plasmodium; history; in vivo imaging; live cell imaging; malaria; microscopy; superresolution
    DOI:  https://doi.org/10.1111/jmi.13384
  11. Front Biosci (Landmark Ed). 2024 Nov 27. 29(12): 402
    The Warburg Effect: Is it Always an Enemy?
    Christos Papaneophytou.
      The Warburg effect, also known as 'aerobic' glycolysis, describes the preference of cancer cells to favor glycolysis over oxidative phosphorylation for energy (adenosine triphosphate-ATP) production, despite having high amounts of oxygen and fully active mitochondria, a phenomenon first identified by Otto Warburg. This metabolic pathway is traditionally viewed as a hallmark of cancer, supporting rapid growth and proliferation by supplying energy and biosynthetic precursors. However, emerging research indicates that the Warburg effect is not just a strategy for cancer cells to proliferate at higher rates compared to normal cells; thus, it should not be considered an 'enemy' since it also plays complex roles in normal cellular functions and/or under stress conditions, prompting a reconsideration of its purely detrimental characterization. Moreover, this review highlights that distinguishing glycolysis as 'aerobic' and 'anaerobic' should not exist, as lactate is likely the final product of glycolysis, regardless of the presence of oxygen. Finally, this review explores the nuanced contributions of the Warburg effect beyond oncology, including its regulatory roles in various cellular environments and the potential effects on systemic physiological processes. By expanding our understanding of these mechanisms, we can uncover novel therapeutic strategies that target metabolic reprogramming, offering new avenues for treating cancer and other diseases characterized by metabolic dysregulation. This comprehensive reevaluation not only challenges traditional views but also enhances our understanding of cellular metabolism's adaptability and its implications in health and disease.
    Keywords:  Warburg effect; cancer metabolism; cellular metabolism; glycolysis; metabolic reprogramming
    DOI:  https://doi.org/10.31083/j.fbl2912402
This page is being maintained by Thomas Krichel. It was last updated on 2025‒01‒05 at 2:02.