bims-toxgon Biomed News
on Toxoplasma gondii metabolism
Issue of 2025–08–24
fifteen papers selected by
Lakesh Kumar, BITS Pilani
  1. A novel YGGT family protein is localized in the apicoplast and is essential for the organelle inheritance.
  2. AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment.
  3. Cross-lineage 5-methylcytosine methylome profiling reveals methylated divergence among Toxoplasma gondii tachyzoites of the three major clonal lineages.
  4. Toxoplasma gondii endodyogeny: how to make perfect daughters.
  5. Anti-Toxoplasma gondii studies of the venom peptide XYP4 from the Lycosa coelestis.
  6. Mitochondrial hyper-acetylation induced by an engineered acetyltransferase promotes cellular senescence.
  7. Sirtuin 3 in diabetic kidney disease: mechanisms and pharmacotherapy.
  8. CREB binding protein (CREBBP): Structure-based perspectives for the development of clinical inhibitors.
  9. Plasmodium falciparum PP1 phosphatase is a key regulator of malaria parasite transmission.
  10. Interactome Profiling of a Lysine Deacetylase Trapping Probe Library Uncovers Crosstalk Between HDAC6 and NF-κB Signaling.
  11. Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.
  12. Discovery of an Atypical Arp2/3 Complex in Malaria Parasites Sheds New Light on Nuclear Actin.
  13. Exploring the metabolic signaling network of GFPT in cancer.
  14. Targeting invasion-associated proteins PfSUB2 and PfTRAMP in Plasmodium falciparum: identification of potential inhibitors via molecular docking.
  15. Molecular detection of Toxoplasma gondii in paraffin blocks from patients diagnosed with various cancers.
  1. Front Cell Infect Microbiol. 2025 ;15 1642716
    A novel YGGT family protein is localized in the apicoplast and is essential for the organelle inheritance.
    Wenqiang Su, Haorong Gu, Jun Zheng, Honglin Jia.
      Toxoplasma gondii is an obligate intracellular apicomplexan parasite. Most apicomplexan parasites contain an endosymbiont-derived organelle called the apicoplast. This organelle is critical for the survival of parasites because it plays a role in several essential metabolic pathways. However, the molecular mechanisms involved in maintaining the apicoplast have not been well understood. In this study, we investigated the function of an apicoplast-residing protein called TgYCAP in the inheritance of the apicoplast. Our results showed that conditional knockdown of TgYCAP severely inhibited the growth of the parasite and disrupted the inheritance of the apicoplast. In addition, the YGGT domain is essential for its function in the apicoplast.
    Keywords:  TgYCAP; Toxoplasma gondii; YGGT family protein; apicoplast; biogenesis
    DOI:  https://doi.org/10.3389/fcimb.2025.1642716
  2. mBio. 2025 Aug 15. e0005225
    AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment.
    Li-Xiu Sun, Meng Wang, Tian-Yu Zhang, Hany M Elsheikha, Zhi-Wei Zhang, Xiao-Nan Zheng, Bao-Quan Fu, Xing-Quan Zhu, Guo-Hua Liu, Jin-Lei Wang.
      Toxoplasma gondii is a widespread protozoan with a complex life cycle, characterized by transitions between various hosts and developmental stages, each tailored to a specific niche within its host. However, the regulatory mechanisms governing these life cycle transitions are not well understood. In this study, we investigated the AP2 factor AP2X-1, which is expressed during the tachyzoite and bradyzoite stages but decreases in the mature merozoite stage. Knockout of ap2X-1 significantly impaired tachyzoite invasion and replication while increasing the frequency of bradyzoite differentiation. As a component associated with the HDAC3/MORC complex, loss of ap2X-1 led to the upregulation of bradyzoite- and sexual stage-specific genes. Single-cell sequencing revealed that the ap2X-1 knockout strain exhibited a mixed population of tachyzoite-, bradyzoite-, merozoite-, and sporozoite-like parasites. Cleavage under targets and tagmentation analysis revealed a substantial overlap between AP2X-1 and the HDAC3/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes. Additionally, assay for transposase-accessible chromatin with high-throughput sequencing analysis demonstrated that AP2X-1 influences chromatin compaction and accessibility, suggesting that AP2X-1 may modulate the function of the HDAC3/MORC complex to facilitate the repression of bradyzoite differentiation and sexual commitment. Loss of ap2X-1 resulted in significant attenuation of T. gondii virulence and decreased brain cyst formation in vivo. These findings identify AP2X-1 as a critical negative regulator of T. gondii sexual development.IMPORTANCEToxoplasma gondii undergoes a complex life cycle characterized by alternating developmental stages. The genetic reprogramming mechanisms driving these stage transitions remain largely unknown. In this study, we identified the AP2 factor AP2X-1 as a critical regulator important for T. gondii growth and life cycle progression. Our findings suggest that AP2X-1 functions as a repressor by modulating the function or influencing the association of the HDAC3/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes, leading to chromatin compaction, restricting DNA accessibility and thereby repressing the transcription of genes required for bradyzoite formation and sexual commitment. Deletion of ap2X-1 significantly reduced T. gondii virulence and its ability to form brain cysts. These findings reveal a previously unknown regulatory pathway controlling sexual development in T. gondii, providing new insights into its underlying mechanisms.
    Keywords:  AP2X-1; HDAC3/MORC complex; Toxoplasma gondii; gene expression; sexual development; transcription
    DOI:  https://doi.org/10.1128/mbio.00052-25
  3. Infect Dis Poverty. 2025 Aug 19. 14(1): 87
    Cross-lineage 5-methylcytosine methylome profiling reveals methylated divergence among Toxoplasma gondii tachyzoites of the three major clonal lineages.
    Xiao-Nan Zheng, Hong-Yu Song, Hany M Elsheikha, Chen-Ran Tian, Xing Tian, Qing Liu, Wen-Bin Zheng, Xing-Quan Zhu.
       BACKGROUND: Toxoplasma gondii is a globally widespread zoonotic parasite, infecting nearly one-third of the human population, often leading to chronic, latent infections. Among the emerging layers of gene regulation, 5-methylcytosine (m5C) has emerged as a pivotal post-transcriptional modification in eukaryotes. Despite its growing recognition in various species, the epitranscriptomic landscape of m5C in the tachyzoite stage of T. gondii remains largely unexplored. To address this gap, we performed the first comprehensive m5C methylation profiling across three major T. gondii genotypes-RH (type I), ME49 (type II), and VEG (type III).
    METHODS: The comparative m5C methylation analysis was carried out using methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA sequencing (RNA-Seq). Differentially m5C-methylated genes (DMMGs) were functionally annotated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. By combining methylation and transcriptomic data, we uncovered strain-specific correlations between m5C modifications and gene expression. Additionally, expression and methylation patterns of potential regulators identified via BLASTP searches were examined. Statistical analyses were determined by one-way ANOVA.
    RESULTS: Our analysis revealed a total of 5129, 4968, and 4577 m5C-methylated genes in RH, ME49, and VEG tachyzoites, respectively, with methylation predominantly enriched in the coding sequences. Comparative analysis across different strains uncovered 1710, 1131, and 784 DMMGs in RH versus ME49, RH versus VEG, and ME49 versus VEG, respectively. Functional enrichment analysis highlighted key biological processes, including catalytic activity, transport, phospholipid metabolism and transcription regulation. Furthermore, KEGG pathway analysis identified critical m5C-regulated processes such as nucleocytoplasmic transport, DNA replication, and ATP-dependent chromatin remodeling. Virulence-associated secretory effectors exhibited hypermethylation in more virulent strains, such as GRA39 and ROP35. Additionally, several putative m5C regulators displayed genotype-specific or conserved expression and methylation patterns.
    CONCLUSIONS: This study presents the first m5C epitranscriptomic atlas of T. gondii tachyzoites, revealing both conserved and genotype-specific mRNA modification networks. These insights significantly increased the understanding of the regulatory role of m5C in T. gondii pathogenesis and open promising avenues for the development of vaccines and therapeutics aimed at combating zoonotic toxoplasmosis.
    Keywords:   Toxoplasma gondii ; 5-methylcytosine; Epitranscriptomic regulation; Methylated RNA immunoprecipitation sequencing; RNA sequencing; Toxoplasmosis
    DOI:  https://doi.org/10.1186/s40249-025-01358-w
  4. Trends Parasitol. 2025 Aug 16. pii: S1471-4922(25)00201-6. [Epub ahead of print]
    Toxoplasma gondii endodyogeny: how to make perfect daughters.
    Maanasa Bhaskaran, Venkat Mudiyam, Mathieu Gissot.
      The pathogenesis of Toxoplasma gondii in humans is largely attributed to its capacity for rapid multiplication via a streamlined division process known as endodyogeny. The assembly of the daughter cell scaffold, occurring through a process termed budding, necessitates strict temporal and spatial regulation. Recent advances have elucidated remarkable details of the early stages of daughter cell formation, underscoring the pivotal role of the apical polar ring during the initial phases. Furthermore, emerging evidence implicates ApiAP2 transcription factors in the regulation of gene expression essential for the synthesis of daughter cell components. This transcriptional control is complemented by post-translational regulatory mechanisms governing both the initiation and maturation of the daughter cell cytoskeleton. Both processes are critical for the successful production of invasive zoites.
    Keywords:  Toxoplasma; apicomplexa; endodyogeny; expansion microscopy; phosphorylation; transcription factor
    DOI:  https://doi.org/10.1016/j.pt.2025.07.012
  5. Toxicon. 2025 Aug 14. pii: S0041-0101(25)00315-0. [Epub ahead of print] 108540
    Anti-Toxoplasma gondii studies of the venom peptide XYP4 from the Lycosa coelestis.
    Dongqian Yang, Xiaohua Liu, Jing Li, Kaijuan Wu, Jing Xie, Yixiao Wang, Zheng Wang, Liping Jiang.
      Toxoplasma gondii (T. gondii) is an intracellular parasite with multiple routes of infection that poses a serious health risk to pregnant women, fetuses, and immunocompromised populations. Currently, clinical drugs in the treatment of toxoplasmosis continue to face challenges such as drug resistance. In the face of this challenge, researchers have gradually focused on the potential medicinal value of animal venoms in the fight against T. gondii, especially venom peptides showing advantages such as high potency, membrane targeting, and immunomodulation. The present study aimed to explore whether XYP4, a peptide derived from the venom of the Lycosa coelestis (L. coelestis), possesses better anti-T. gondii activity and its mode of action. The experimental results showed that XYP4 is an amphiphilic cationic linear polypeptide with an α-helix, which can exert anti-toxoplasma activity at low concentrations, affecting the lytic cycle. This polypeptide showed moderate survival benefits in mice infected with T. gondii. The main modes of action of XYP4 include inhibition of tachyzoites' intracellular proliferation, modulation of inflammatory factor expression in the host cells, and disruption of tachyzoite membrane integrity.
    Keywords:  Lycosa coelestis; Toxoplasma gondii; XYP4; membrane-targeted
    DOI:  https://doi.org/10.1016/j.toxicon.2025.108540
  6. iScience. 2025 Sep 19. 28(9): 113233
    Mitochondrial hyper-acetylation induced by an engineered acetyltransferase promotes cellular senescence.
    Tadahiro Shimazu, Ayane Kataoka, Takehiro Suzuki, Naoshi Dohmae, Yoichi Shinkai.
      Protein acetylation plays crucial roles in diverse biological functions, including mitochondrial metabolism. Although SIRT3 catalyzes the removal of acetyl groups in mitochondria, the addition of the acetyl groups is thought to be primarily controlled in an enzyme-independent manner due to the absence of potent acetyltransferases. In this study, we developed an engineered mitochondria-localized acetyltransferase, named engineered mitochondrial acetyltransferase (eMAT). eMAT localized in the mitochondrial matrix and introduced robust global protein lysine acetylation, including 413 proteins with 1,119 target lysine residues. Notably, 74% of the acetylated proteins overlapped with previously known acetylated proteins, indicating that the eMAT-mediated acetylation system is physiologically relevant. Functionally, eMAT negatively regulated mitochondrial energy metabolism, inhibited cell growth, and promoted cellular senescence, suggesting that mitochondrial hyper-acetylation drives metabolic inhibition and cellular senescence. SIRT3 counteracted eMAT-induced acetylation and metabolic inhibition, restored cell growth, and protected cells from senescence, highlighting the contribution of SIRT3 in maintaining energy metabolism and preventing cellular senescence.
    Keywords:  Metabolic flux analysis; Metabolomics; Protein
    DOI:  https://doi.org/10.1016/j.isci.2025.113233
  7. Ren Fail. 2025 Dec;47(1): 2543927
    Sirtuin 3 in diabetic kidney disease: mechanisms and pharmacotherapy.
    Yinfeng Chen, Ying Wang, Dongrong Yu, Hailing Zhao, Ping Li.
      Diabetic kidney disease (DKD) is a microvascular complication of diabetes and a major cause of kidney failure; current treatment methods still need improvement. Sirtuin 3 (SIRT3) is an NAD+-dependent protein deacetylase located in the mitochondria, where it regulates the activity and biological functions of diverse proteins and influences various mitochondrial functions via deacetylation. Increasing research indicates that SIRT3 holds promise as a therapeutic target for DKD. This review examines SIRT3's impact on mitochondrial functions, including mitochondrial biogenesis, autophagy, dynamics, oxidative homeostasis, and energy metabolism. We summarize that SIRT3 delays the progression of DKD by inhibiting oxidative stress, reducing inflammation, regulating cell death, and modulating energy metabolism. Finally, we categorize the applications of SIRT3 activators in renal diseases. In summary, this review provides a thorough understanding of SIRT3's functional role in DKD and proposes a potential therapeutic approach pending clinical validation.
    Keywords:  Sirtuin 3; diabetic kidney disease; mitochondrion; molecular mechanisms; pharmacotherapy
    DOI:  https://doi.org/10.1080/0886022X.2025.2543927
  8. Transl Oncol. 2025 Aug 18. pii: S1936-5233(25)00238-4. [Epub ahead of print]61 102507
    CREB binding protein (CREBBP): Structure-based perspectives for the development of clinical inhibitors.
    Rongxing Liu, Jiaxin Li, Qing Nian, Gao Tu, Zhenqiang Wang, Rong Zhang, Guobing Li.
      Acetylation is an essential process in biological processes. In tissues, protein acetylation occurs mainly at lysine (K) residues. The balance between acetylation and deacetylation is under the control of two enzyme families, histone acetyltransferase (HAT) and histone deacetylase (HDAC), respectively. Although there are many highly selective and potent HDAC inhibitors (such as romidepsin and belinostat), few HAT inhibitors are undergoing clinical trials. CREBBP, also known as CBP, is a member of the HAT family and plays a key role in several diseases, especially in hematopoietic malignancies, through the modulation of different signaling pathways. Studies have shown that CBP is highly expressed and activated in a variety of different tumors; therefore, its inhibitors have attracted increasing research attention. In this review, we discuss the importance of the structure of CBP in the development of potential inhibitors to provide a reference for the development of new selective CBP inhibitors.
    Keywords:  Acetylation; CBP; Inhibitor; Structure
    DOI:  https://doi.org/10.1016/j.tranon.2025.102507
  9. mBio. 2025 Aug 18. e0087425
    Plasmodium falciparum PP1 phosphatase is a key regulator of malaria parasite transmission.
    Ludivine Royer, Emma Colard-Itté, Tatyana Tavella, Audrey Lorthiois, Stéphane Goussin, Marie-Esther N'Dri, Reem Sabra, Auréline Deiss, Sabine Thiberge, Mauld H Lamarque, Catherine Lavazec.
      For the successful transmission of malaria parasites from humans to mosquitoes, Plasmodium falciparum gametocytes must remain in the bloodstream long enough to be taken up by a mosquito. Once ingested, they are then activated into gametes to continue the parasite life cycle in the mosquito midgut. Both persistence of gametocytes in the blood and their activation into gametes are tightly regulated by phospho-signaling. While the serine-threonine phosphatase PfPP1 is an essential enzyme for asexual blood stage parasite proliferation, its role during transmission of sexual stages remains elusive. Here, we employed a conditional depletion strategy to conduct a functional analysis of PfPP1 during gametocyte development, gamete formation, and transmission to mosquitoes. We show that PfPP1 regulates the deformability and the permeability of mature gametocyte-infected erythrocytes through the dephosphorylation of protein kinase A (PKA) substrates, thus highlighting a key role for PfPP1 in modulating the host cell mechanical properties, which are crucial for gametocyte persistence in the bloodstream. We also provide evidence that PfPP1 controls crucial steps of gametocyte activation via stimulation of the cyclic GMP (cGMP)/protein kinase G (PKG) pathway. Collectively, these results underscore the pivotal role of PfPP1 in the transmission of P. falciparum to the mosquito during both gametocyte development and gamete formation.
    IMPORTANCE: The protein phosphatase PP1 is a major contributor to total cellular phosphatase activity in eukaryotes and plays a critical role during various cellular processes. Here, we have unraveled novel mechanisms regulated by the phosphatase PfPP1 in the human malaria parasite Plasmodium falciparum. While PfPP1 is known to be essential for the parasite's asexual proliferation, in the present study, we demonstrate that PfPP1 is also required during the sexual parasite stages, called gametocytes, that ensure parasite transmission from humans to mosquitoes. PfPP1 regulates the mechanical properties of the gametocyte-infected host cell, a process necessary for gametocyte persistence in blood circulation. Moreover, PfPP1 also contributes to the activation of gametocytes into gametes, the stages that pursue the parasite life cycle in mosquitoes. In addition to providing insights into novel mechanisms involved in parasite transmission, this study also highlights the possibility of interfering with the PfPP1 signaling pathway for blocking malarial parasite transmission.
    Keywords:  PP1; Plasmodium falciparum; cell signaling; gametocytes; gametogenesis; phosphatase; transmission
    DOI:  https://doi.org/10.1128/mbio.00874-25
  10. Angew Chem Int Ed Engl. 2025 Aug 18. e202510967
    Interactome Profiling of a Lysine Deacetylase Trapping Probe Library Uncovers Crosstalk Between HDAC6 and NF-κB Signaling.
    Julian Seidel, Caroline Schönfeld, Julia Sindlinger, Jürgen Eirich, Sören Kirchgäßner, Nina Kreienkamp, Klaus Schulze-Osthoff, Iris Finkemeier, Stephan Hailfinger, Dirk Schwarzer.
      Lysine or histone deacetylases (HDACs) remove acetyl groups from lysine residues of numerous proteins, thereby regulating their function and activity. HDAC6 is involved in multiple cellular processes, yet its protein interaction network remains poorly understood. To uncover novel HDAC6 substrates, we performed an acetylome analysis of HDAC6 knockdown cells, which served as a basis for the design of an HDAC6-trapping peptide library containing hydroxamic acids. Most probes enriched HDAC6 from cell lysates stronger than HDAC1. Proteomic profiling of the trapping probes revealed a preferential enrichment of HDAC6 and resulted in the identification of novel putative HDAC6 interaction partners. Among those were several components of the pro-inflammatory transcription factor NF-κB that were independently confirmed as HDAC6 binders. Mechanistically, HDAC6 counteracted NF-κB activity induced upon p300-catalyzed acetylation of NF-κB p50. These findings indicate a potential anti-inflammatory function of HDAC6 in NF-κB signaling.
    Keywords:  HDAC inhibitor; HDAC6; Lysine acetylation; NF‐κB; Peptide probes
    DOI:  https://doi.org/10.1002/anie.202510967
  11. Biochem Soc Trans. 2025 Aug 18. pii: BST20253050. [Epub ahead of print]
    Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.
    Nicoletta T Basilone, Viveka M Pimenta, Gary S Shaw.
      Parkin, a Ring-InBetweenRING-Rcat E3 ubiquitin ligase, plays a vital role in the clearance of damaged mitochondria (mitophagy) by ubiquitylating a broad spectrum of mitochondrial proteins. Mutations in the PRKN gene alter parkin ubiquitylation activity and are a leading cause of early-onset Parkinsonism, underlining its critical function in maintaining mitochondrial homeostasis. The structures, substrates, and ubiquitylation mechanisms used by parkin in mitophagy are well established. Yet, early studies as well as more recent proteomics studies identify alternative substrates that reside in the cytosol or other cellular compartments, suggesting potential roles for parkin beyond mitophagy. In addition to its well-documented activation via S65 phosphorylation, numerous other post-translational modifications (PTMs) have been identified in parkin. Some of these modifications have the potential to serve key regulatory mechanisms, perhaps fine-tuning parkin activity or potentially signaling the involvement in alternative cellular pathways beyond mitochondrial quality control. This review examines the canonical mechanism of parkin-mediated ubiquitylation while also exploring alternative regulatory influences that may modulate its enzyme activity. By analyzing emerging evidence on PTMs including phosphorylation, acetylation, ubiquitylation, oxidation, and interaction with alternative activating molecules, we highlight the broader functional landscape of parkin and its implications for cellular stress response.
    Keywords:  Parkinson's disease; mitochondrial dysfunction; parkin; protein structure; ubiquitin ligases
    DOI:  https://doi.org/10.1042/BST20253050
  12. Cytoskeleton (Hoboken). 2025 Aug 19.
    Discovery of an Atypical Arp2/3 Complex in Malaria Parasites Sheds New Light on Nuclear Actin.
    Franziska Hentzschel, Friedrich Frischknecht, Matthias Marti.
      The Arp2/3 complex is a key actin nucleator essential for cytoskeletal dynamics in eukaryotes. Previously believed absent in apicomplexan parasites, we recently identified an atypical Arp2/3 complex in malaria parasites consisting of five divergent subunits and a putative kinetochore-associated factor. This complex ensures proper kinetochore-spindle attachment during male gametogenesis, likely by nucleating actin at the mitotic spindle. Disruption of Arp2/3 function or actin polymerization leads to defective DNA segregation into gametes and developmental arrest of the parasite in the mosquito. Our findings reveal unexpected diversity in Arp2/3 complex composition and function, highlighting specialized adaptations in malaria parasites and expanding our understanding of the Arp2/3 complex and actin functions during mitosis. Here, we discuss some of the open questions that need to be addressed to fully understand the molecular mechanism of this unusual Arp2/3 complex and its essential role in malaria transmission.
    Keywords:   Plasmodium ; Arp2/3 complex; actin; mitosis
    DOI:  https://doi.org/10.1002/cm.70030
  13. Cell Death Discov. 2025 Aug 19. 11(1): 388
    Exploring the metabolic signaling network of GFPT in cancer.
    Chibuzo Sampson, Pengfei Li, Yiqian Wang, Jing Liu, Jing Lv, Tian Xia, Hai-Long Piao, Yegang Ma.
      Metabolic homeostasis is essential for cellular function in living organisms. In cancer cells, metabolic processes are reprogrammed to meet the energy demands and biosynthetic needs for rapid growth. This reprogramming enhances nutrient flux through the glycolytic pathway, supporting ATP production and branching into pathways that synthesize macromolecules required for cell proliferation. One critical branching pathway is the hexosamine biosynthesis pathway (HBP), which, driven by metabolic reprogramming, facilitates the synthesis of uridine-5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), a glycosylation substrate. This pathway is regulated by the rate-limiting enzyme glutamine-fructose-6-phosphate transaminase (GFPT), a key controller of cellular UDP-GlcNAc levels and protein glycosylation. Dysregulation of GFPT is linked to metabolic disorders, like in diabetes, and it is also frequently upregulated in cancers. Given that GFPT plays a pivotal role in cancer metabolism, elucidating its regulatory interactions with other metabolic signaling pathways under metabolic stress is crucial to identifying therapeutic vulnerabilities in cancer. This review discusses the interaction network of GFPT with other metabolic pathways, its role in nutrient sensing, and the implications of GFPT deregulation in cancer.
    DOI:  https://doi.org/10.1038/s41420-025-02687-3
  14. BMC Infect Dis. 2025 Aug 19. 25(1): 1038
    Targeting invasion-associated proteins PfSUB2 and PfTRAMP in Plasmodium falciparum: identification of potential inhibitors via molecular docking.
    Esther O Okafor, Mercy Bella-Omunagbe, Temitope Elugbadebo, Titilope M Dokunmu, Ezekiel Adebiyi.
      Plasmodium falciparum subtilisin-like protease 2 (PfSUB2) is responsible for processing Plasmodium falciparum thrombospondin-related apical merozoite protein (PfTRAMP). These proteins are essential for asexual blood stage growth and RBC invasion and have, therefore, been identified as potential drug targets. This study predicted the three-dimensional structure of PfSUB2 and PfTRAMP and identified potential inhibitors using molecular docking methods. Five hundred nineteen compounds were docked against both proteins with AutoDock Vina in PyRx. Compounds 139,974,934 and 154,414,021 exhibited better binding affinities when compared to the standard inhibitors, PMSF, which highlights them as suitable inhibitors and potential antimalarials targeting PfTRAMP and PfSUB2. It also highlights 155,204,487 as a compound with dual antimalarial target potential, exhibiting a better binding affinity to PfTRAMP and PfSUB2. The study recommends 139,974,934, 154,414,021, and 155,204,487 as possible compounds for antimalarial drug development.
    Keywords:   Plasmodium falciparum ; Malaria; Molecular Docking; Subtilisin-like protease 2; Thrombospondin-related apical merozoite protein
    DOI:  https://doi.org/10.1186/s12879-025-11380-w
  15. Trans R Soc Trop Med Hyg. 2025 Aug 18. pii: traf083. [Epub ahead of print]
    Molecular detection of Toxoplasma gondii in paraffin blocks from patients diagnosed with various cancers.
    Azadeh Pourahmad, Babak Shirazi Yeganeh, Amir Abdoli, Zahra Kargar Jahromi, Akbar Kazemi, Ali Taghipour, Ali Rezanezhad, Hassan Rezanezhad.
      This study aimed to investigate the prevalence of Toxoplasma gondii DNA in cancer tissue samples and explore potential associations with different cancer types. A total of 338 paraffin blocks from patients diagnosed with nine different cancers, including brain, lung, colon, breast, testis, prostate, uterus, ovary and eye, were analysed. The age distribution of the patients ranged from ≤30 to >70 y. The analysed sample consisted of 204 female and 134 male subjects. The molecular analysis revealed an overall prevalence of T. gondii DNA presence in 9.75% (33 cases) of the cancer tissue samples: 19 lung tissue samples, 6 colon samples, 5 breast samples and 1 sample each from the testis, prostate and uterus. Conversely, no T. gondii DNA was detected in the brain, ovary and eye samples. Statistical analysis using the χ2 test indicated a significant association between T. gondii and the type of cancer tissue, with a higher frequency in lung and colon tissues (p<0.001). However, there was no significant correlation observed between T. gondii infection and age or gender. These findings highlight potential links between T. gondii infection and specific cancer types, suggesting a need for further research to elucidate the underlying mechanisms and implications for cancer pathogenesis. Understanding the role of T. gondii in cancer development may offer new insights into preventive strategies and targeted treatments for T. gondii-associated malignancies. Further investigations are warranted to validate these associations, expand the sample size and explore the clinical significance of T. gondii infection in cancer patients.
    Keywords:   Toxoplasma gondii ; cancer; molecular detection
    DOI:  https://doi.org/10.1093/trstmh/traf083
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