bims-toxgon 2026-09-13 papers

bims-toxgon

Biomed News

on Toxoplasma gondii metabolism

Issue of 2026–09–13
thirteen papers selected by
Lakesh Kumar, BITS Pilani

Toxoplasma gondii SIR2A Promotes Tachyzoite Invasion via Lysine Deacetylase Activity.
Organization of Myosin H in the Apical Complex of Toxoplasma gondii Revealed by 3D Single-Molecule Super-Resolution Microscopy.
Toxoplasma gondii infection disrupts secondary bile acid transformation in feline gut microbiota.
Investigation of the classical histone deacetylases and sirtuins using peptide technologies.
Genome-resolved analysis reveals disruption of gut microbial vitamin B and K2 biosynthesis during Toxoplasma gondii infection in mice.
Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.
Endogenous Amphiregulin promotes muscle repair and function through expansion of fibro-adipogenic progenitors during chronic Toxoplasma gondii infection in mice.
Pyruvylation expands the redox repertoire of lysine acylation.
TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei.
Metabolite-driven protein modifications in immune signaling: from established principles to emerging pyruvylation.
Biological functions of FASN in tumor lipid metabolism and research advances in its covalent modifications.
Design, synthesis, and screening of novel thienopyrimidine derivatives as PI3K/HDAC dual inhibitors against cervical cancer cells.
Stage-specific expression and localization of ETRAMP4 during gametocyte development in the malaria parasite Plasmodium falciparum.

FASEB J. 2026 Sep 30. 40(18): e72295

Toxoplasma gondii SIR2A Promotes Tachyzoite Invasion via Lysine Deacetylase Activity.

Yantao Wu, Xiaona Liu, Xin Tian, Yangyang Xie, Yunjia Wu, Xiaozi Zheng, Xin Hu, Qianqian Hua, Wei Zhao, Yani Mou, Feng Tan.

  Accumulating evidence indicates that reversible acetylation modifications are critically involved in the regulation of gene expression, metabolic pathways, and the tachyzoite transformation in Toxoplasma gondii. Silent information regulator 2 (SIR2), an NAD+-dependent lysine deacetylase, contributes to the maintenance of specific silent chromatin domains in mammals. However, its exact functions in T. gondii are unclear. In this study, we systematically analyzed two SIR2 homologs, TgSIR2A, and TgSIR2B, in T. gondii. Our findings demonstrate that TgSIR2A exerts a more pronounced effect on tachyzoite growth compared to TgSIR2B. TgSIR2A is predominantly localized in the cytoplasm of tachyzoites and exhibits cell cycle-dependent expression. Conditional depletion of TgSIR2A significantly impairs tachyzoite invasion. Using gain- and loss-of-function approaches, we confirmed that the histidine at position 228 is essential for TgSIR2A's catalytic activity. Mutation of this residue elevates global acetylation levels and compromises tachyzoite invasion capacity. Furthermore, acetylated proteomics and interaction analyses suggest that TgSIR2A may regulate gene expression, protein translation, and maturation processes in tachyzoites. Notably, TgBip, an ER-associated chaperone, may be a substrate of TgSIR2A. Collectively, our results indicate that TgSIR2A plays an important role in tachyzoite invasion via its lysine deacetylase activity, making it a potential target for treating T. gondii infections.

Keywords:   Toxoplasma gondii ; deacetylase; silent information regulator 2

DOI:  https://doi.org/10.1096/fj.202602184R
Biophys J. 2026 Sep 10. pii: S0006-3495(26)00642-9. [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 MyoH within the apical complex. Labeling of the N- and C-termini 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 fibrils 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.

DOI: https://doi.org/10.1016/j.bpj.2026.09.012
Appl Environ Microbiol. 2026 Sep 11. e0067426

Toxoplasma gondii infection disrupts secondary bile acid transformation in feline gut microbiota.

Lu-Yao Tang, He Zhang, Ji-Xin Zhao, Ying-Qian Gao, Xuancheng Zhang, Shi-Chen Xie, Zhi Zheng, Xing-Quan Zhu, Xiao-Xuan Zhang, Changyou Xia, Rui Liu, He Ma.

  Bile acid (BA) transformation relies on gut microbiota and is vulnerable to Toxoplasma gondii infection, yet feline microbial BA-transforming capacity upon toxoplasmosis remains unclear. Here, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. The results revealed that the feline gut microbiome harbored widespread genetic potential for BA transformation but lacked a complete 7α-dehydroxylation pathway due to the absence of the key gene baiE. The BA transformation-related genomes (2,045 in total) were predominantly from the phyla Bacillota_A and Actinomycetota, among which only 37 encoded baiB, all belonging to Bacillota_A. The distribution of BA transformation-related genes varied across intestinal regions: genes encoding 7α-HSDH were primarily enriched in the small intestine, whereas genes encoding 3α-HSDH, baiCD, and baiH were more abundant in the large intestine. Additionally, the abundance of genes encoding BSH and 3α-HSDH increased significantly in the small intestine on day 3 post-infection, accompanied by increases in the phylum Bacillota_C and genera such as Blautia_A, Enterococcus_E, and Ligilactobacillus. Serum metabolomics revealed a significant increase in cholesterol levels post-infection, supporting the impact of T. gondii infection on intestinal BA transformation. These findings illustrated that the feline gut microbiota played an important role in BA transformation and that T. gondii infection disrupted the microbial potential for secondary BA transformation. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.
IMPORTANCE: Bile acid (BA) transformation plays a critical role in host metabolism and immune regulation. Although studies on BA transformation are increasing, the capacity for BA transformation within the feline gut microbiota and the impact of Toxoplasma gondii infection on this capacity remain unclear. To bridge this gap, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. Our findings revealed that the feline gut microbiome lacked a complete 7α-dehydroxylation pathway, and the specific functions involved in BA transformation may differ between the small and large intestines. Furthermore, integrated metagenomic and serum metabolomic analyses suggested that T. gondii infection disrupted BA transformation capacity in the small intestine. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.

Keywords:  Toxoplasma gondii; bile acid transformation; feline gut microbiota; metagenomic analysis

DOI:  https://doi.org/10.1128/aem.00674-26
Cell Chem Biol. 2026 Sep 08. pii: S2451-9456(26)00319-3. [Epub ahead of print]

Investigation of the classical histone deacetylases and sirtuins using peptide technologies.

Joseph M Rogers, Christian A Olsen.

  Histone deacetylase (HDAC) enzymes are hydrolases that remove acyl-based modifications from the side chains of lysine residues in our proteome. Originally named after their first identified substrates, the acetylated lysine residues in histone proteins, it has now become evident that individual isozymes of the HDAC class have different protein targets, cellular localization, and ε-N-acyllysine substrate specificities. To help elucidate the activities of the different HDACs, researchers have developed a variety of peptide-based tools, providing mechanistic insights and substrate preferences of the HDACs. Due to their central regulatory roles, HDACs have been investigated as drug targets, resulting in several drugs approved for clinical use, including the naturally occurring peptide, romidepsin, spurring the interest in peptide-based inhibitors. In this review, we provide a concise overview of important discoveries enabled by peptide chemistry in the HDAC field and discuss the future potential of high-throughput peptide technologies for HDAC profiling and inhibitor discovery.

Keywords:  enzyme inhibitors; enzyme substrates; mRNA display; peptide microarrays; post-translational modifications

DOI:  https://doi.org/10.1016/j.chembiol.2026.08.009
Microbiol Spectr. 2026 Sep 08. e0156426

Genome-resolved analysis reveals disruption of gut microbial vitamin B and K2 biosynthesis during Toxoplasma gondii infection in mice.

Hai-Long Yu, Hany M Elsheikha, Hai-Ping Wang, Ying-Qian Gao, Rui Liu, He Ma, Jing Jiang, Ying Li, Xiao-Xuan Zhang.

  Toxoplasma gondii infection remodels the gut microbiome, yet its impact on microbial vitamin biosynthetic potential and host redox metabolism remains unclear. Here, we integrated mouse gut metagenomes with publicly available metagenome-assembled genomes (MAGs) to construct a genome-resolved atlas of B-vitamin and vitamin K2 biosynthesis. From 45,697 MAGs, we curated 4,771 representative genomes, of which 2,682 met high-quality criteria (completeness ≥90%, contamination <5%). Functional annotation identified 229,717 vitamin-related genes corresponding to 177 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs across de novo pathways for eight B vitamins, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and vitamin K2. Among the high-quality genomes, 1,665 encoded complete de novo pathways for at least one vitamin, highlighting functional specialization and community-level complementarity. Transcripts per million-normalized metagenomic read counts revealed significant differences in KEGG ortholog abundances across six of the nine vitamin pathways. Reanalysis of metagenomic data from infected mice (acute, chronic, and control; n = 10 per group) revealed a stage-dependent reduction in α-diversity of vitamin biosynthesis pathways during acute infection, and a clear β-diversity separation from chronic and control groups. Core niacin biosynthesis genes (nadB, nadA, nadC) displayed phylum-specific redistribution, indicating selective remodeling of microbial NAD+ precursor production under infection-induced metabolic stress. These results suggest that T. gondii infection disrupts cooperative vitamin biosynthetic networks while specifically modulating niacin pathways linked to host NAD+ metabolism.
IMPORTANCE: Gut microbes can synthesize essential vitamins, but how infection alters this function is poorly understood. By integrating mouse gut metagenomes with genome-resolved microbial data, we show that Toxoplasma gondii infection reshapes the vitamin biosynthetic potential of the gut microbiome in a stage-dependent manner. Acute infection reduces the diversity of vitamin biosynthesis pathways and shifts the taxonomic distribution of key niacin biosynthesis genes involved in microbial NAD+ precursor production. These findings identify vitamin metabolism, especially niacin-related pathways, as a sensitive functional axis of microbiome remodeling during infection. Our work links microbial taxonomic changes to functional metabolic consequences and suggests that microbiome-mediated regulation of NAD+-related metabolism may contribute to host redox adaptation during T. gondii infection.

Keywords:  B vitamins; Toxoplasma gondii; gut microbiome; metagenome-assembled genomes; mouse; niacin; vitamin K2

DOI:  https://doi.org/10.1128/spectrum.01564-26
Sci Adv. 2026 Sep 11. 12(37): eaee4935

Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.

Julianna G Supplee, Pedro Costa-Pinheiro, Karl Wessendorf-Rodriguez, Stephanie Stransky, Qihua Yang, Christina Demetriadou, Nivitha Murali, Joy Li, Jennifer L Pennise, Mariola M Marcinkiewicz, Simone Sidoli, Nathaniel W Snyder, Christian M Metallo, Ronen Marmorstein, Kathryn E Wellen.

The cell nucleus is an active metabolic site. Numerous enzymes best known for their roles in cytosolic or mitochondrial pathways also function in the nucleus, where they contribute to gene regulation and DNA replication and repair. Although metabolites can diffuse through nuclear pores, it remains unclear the extent to which the nucleus and cytosol operate as continuous versus distinct metabolic spaces. Both compartments require acetyl-CoA-for example, for histone acetylation and lipid synthesis-and the acetyl-CoA generating enzyme ATP-citrate lyase (ACLY) resides in both locations, but the significance of its dual localization is incompletely understood. Using cell lines in which ACLY is localized to either compartment, we find that ACLY in either location supports fatty acid synthesis and histone acetylation, yet compartment-localized ACLY enables finer control. Nuclear ACLY preserves histone H3K23 acetylation under glucose limitation and modulates specific transcriptional programs, whereas cytosolic ACLY most efficiently supports lipid biosynthetic fluxes. Thus, local synthesis defines a preferential metabolic fate, providing more precise regulation.

DOI: https://doi.org/10.1126/sciadv.aee4935
Front Microbiol. 2026 ;17 1854938

Endogenous Amphiregulin promotes muscle repair and function through expansion of fibro-adipogenic progenitors during chronic Toxoplasma gondii infection in mice.

Ronzon Shihab, Andrea Alfaro-Chacon, Monica Humby, Caleb Buerger, Elizabeth A Wohlfert.

  Skeletal muscle regeneration relies on coordinated interactions between immune cells and resident stem cell populations. While most studies have focused on sterile injury, the impact of infections on muscle repair remains less understood. Toxoplasma gondii, a widespread parasite that establishes chronic infection in skeletal muscle and also the central nervous system, induces myositis, fibrosis, and loss of muscle function. In mice, a natural intermediate host, chronic infection sustains a robust Th1 response dominated by IFNγ-producing CD4+ and CD8+ T cells. Regulatory T cells (Tregs), which normally promote resolution of inflammation, instead adopt a pathogenic phenotype, increasing inflammation and impairing repair. Amphiregulin (Areg), a ligand of the epidermal growth factor receptor, has been implicated in tissue repair by enhancing Treg function, promoting macrophage polarization, and supporting mesenchymal differentiation. While exogenous Areg improves muscle function during chronic T. gondii infection, the role of endogenous Areg remains unknown. Here, we used Areg-deficient mice to investigate its contribution to muscle repair during chronic infection. We show that Areg deficiency impaired Areg deficiency impaired fibro-adipogenic progenitor (FAP) expansion, reduced IFNγ-producing CD8+ T cells, and diminished the frequency of Tbet+ Tregs. Additionally, following CTX injury, Areg-deficient mice, particularly females, exhibited impaired regeneration characterized by smaller, more heterogeneous myofibers, and increased damaged area. These findings reveal a critical role for endogenous Areg in timely FAP expansion, proper effector and regulatory T cell polarization, and efficient muscle regeneration in the setting of chronic T. gondii infection.

Keywords:  Amphiregulin; Toxoplasma gondii; fibro- adipogenic progenitor; immune response; inflammation; pathology

DOI:  https://doi.org/10.3389/fmicb.2026.1854938
Trends Biochem Sci. 2026 Sep 07. pii: S0968-0004(26)00253-7. [Epub ahead of print]

Pyruvylation expands the redox repertoire of lysine acylation.

Jun Seo Park, Sung Joong Lee.

  Song et al. establish lysine pyruvylation (Kpy) as an acylation response to glycolytic flux and pyruvate availability, detect pyruvyl-CoA, implicate histone acetyltransferase 1 and p300 as writers and sirtuin 3 as an eraser, and link promoter-associated histone Kpy to transcriptional regulation, defining a distinct C3 acylation alongside lactylation at the redox-coupled pyruvate-lactate node.

Keywords:  acylation; epigenetics; lactate dehydrogenase; post-translational modification; pyruvylation

DOI:  https://doi.org/10.1016/j.tibs.2026.08.008
PLoS Pathog. 2026 Sep 08. 22(9): e1014582

TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei.

Himadri Shukla, Nirdosh, Satish Mishra.

Malaria parasites must undergo complex developmental transitions to complete their life cycle and transmit between vertebrate and mosquito hosts. These transitions are tightly regulated by protein phosphorylation events, yet the specific kinases involved remain poorly characterized. Here, we investigate the role of a previously uncharacterized tyrosine kinase-like protein, TKL3, in the rodent malaria parasite Plasmodium berghei. We show that TKL3 is expressed in blood stages, schizonts, gametocytes, zygotes, and ookinetes and localizes to the cytoplasm. Targeted disruption of the TKL3 gene impairs asexual blood-stage growth, male gamete fertility, and consequently compromises ookinete development. Although oocyst numbers are significantly reduced in mosquitoes, the sporozoites that do form are morphologically normal, retain hepatocyte infectivity, and complete liver-stage development. However, TKL3 knockout sporozoites showed delayed blood-stage patency due to reduced asexual replication. These findings identify TKL3 as an important regulator of parasite growth and transmission, providing new insights into kinases involved in the Plasmodium life cycle.

DOI: https://doi.org/10.1371/journal.ppat.1014582
Front Immunol. 2026 ;17 1912474

Metabolite-driven protein modifications in immune signaling: from established principles to emerging pyruvylation.

Ziye Zhang, Mingze Xu, Sen Zhang, Zhikun Zhang, Hongguang Zhang, Zhenjie Wang, Min Zhu, Hongchang Zhao.

   Background: Immune signaling is tightly coupled to cellular metabolic state. Beyond supplying energy, metabolites can directly regulate immune responses by driving post-translational modifications of proteins and chromatin, shifting immunometabolism toward a model in which metabolic state encodes signaling outputs.
Findings: Protein pyruvylation has recently emerged as a metabolite-responsive lysine modification linking glycolytic metabolism to both immune signaling and transcriptional regulation. Established examples, including histone lactylation and acylation marks linked to acetyl-CoA and crotonyl-CoA, illustrate how metabolite availability shapes chromatin state and transcriptional competence. A recent Cell study showed that high glucose-enhanced glycolysis and pyruvate kinase M2 activity promotes STAT1 pyruvylation at Lys201, thereby disrupting STAT1-STAT2 interaction and suppressing type I interferon signaling. Complementing this signaling-centered mechanism, a subsequent Nature Metabolism study systematically characterized a broader lysine pyruvylation landscape, identified histone and non-histone substrates, linked pyruvylation to glycolytic flux and pyruvyl-CoA metabolism, and implicated HAT1 and p300 as pyruvylation writers and SIRT3 as an eraser. Together, these findings expand pyruvylation from a single signaling event into an emerging metabolite-responsive regulatory system operating across protein signaling and chromatin-associated transcriptional control. In this review, we summarize the conceptual framework of metabolite-driven protein modifications, compare established marks, and discuss the remaining questions surrounding pyruvylation chemistry, enzyme and substrate specificity, reader mechanisms, compartmentalization, detection strategies, physiological relevance, and potential immunopharmacological implications.
Conclusions: Metabolite-driven protein modifications represent an important regulatory layer linking metabolic rewiring to immune reprogramming. Elucidating the chemistry, regulatory machinery, substrate landscape, and physiological functions of pyruvylation will not only advance our understanding of immunometabolism but may also facilitate the development of metabolite-based biomarkers and therapeutic strategies for inflammatory and immune-related disease.

Keywords:  acetylation; crotonylation; immunometabolism; immunopharmacology; lactylation; pyruvylation

DOI:  https://doi.org/10.3389/fimmu.2026.1912474
Eur J Cell Biol. 2026 Sep 06. pii: S0171-9335(26)00044-0. [Epub ahead of print]105(4): 151573

Biological functions of FASN in tumor lipid metabolism and research advances in its covalent modifications.

Wei Duan, Na Jiang, Yan Wang, Xinyi Li, Chang Liu, Xinghui Liu.

  De novo lipogenesis (DNL) operates as a core metabolic pathway in cellular lipid homeostasis, yet its central effector enzyme fatty acid synthase (FASN) undergoes aberrant overexpression and hyperactivation in tumors and metabolic disorders. Herein, we systematically outline the versatile functions of FASN in tumor lipogenic metabolism and summarize recent advances in its covalent regulatory modifications. We highlight nucleic acids methylation modifications, acetylation, ubiquitination, glycosylation, ubiquitin-like modification, palmitoylation and phosphorylation modifications as an integrated network that tune FASN stability, catalytic activity, and subcellular localization. These modifications exhibit extensive crosstalk and disease-specific heterogeneity, offering potential molecular targets for therapeutic intervention in cancer and metabolic diseases.

Keywords:  Covalent modification; FASN; Lipid metabolism; Methylation; Post-translational modification; Ubiquitination

DOI:  https://doi.org/10.1016/j.ejcb.2026.151573
Eur J Med Chem. 2026 Sep 08. pii: S0223-5234(26)00760-9. [Epub ahead of print]320 119315

Design, synthesis, and screening of novel thienopyrimidine derivatives as PI3K/HDAC dual inhibitors against cervical cancer cells.

Weixu Wang, Naziyila Shayilan, Xijin Qi, Cheng Ma.

  Phosphatidylinositol 3-kinase (PI3K) and histone deacetylase (HDAC) inhibition is a potential tumor treatment strategy, including for cervical cancer. Herein, a novel series of thienopyrimidine derivatives was rationally designed, synthesized, and biologically evaluated as dual PI3K/HDAC inhibitors targeting cervical cancer. Compound B7 was evaluated for its inhibitory effects across the entire PI3K and HDAC families, and exhibited strong PI3Kα (IC50 = 25.41 ± 5.23 nM), PI3Kδ (IC50 = 41.58 ± 4.54 nM), HDAC6 (IC50 = 29.35 ± 3.41 nM), and moderate HDAC8 inhibition (IC50 = 157.27 ± 6.18 nM). In cellular assays, B7 suppressed the proliferation of four cervical cancer cell lines (HeLa, SiHa, Ca-Ski, and ME-180) with IC50 values below 5 μM. And B7 showed moderate selectivity in normal L-O2 and HEK-293T cell viability with IC50 values around 15 μM. Mechanistically, B7 induced HeLa cell S-phase arrest and apoptosis. Notably, it blocked the PI3K/AKT pathway and upregulated α-tubulin and SMC3 acetylation without altering Ac-H3/H4 levels, consistent with its enzymatic selectivity for HDAC6/8 over Class I HDACs. Molecular dynamics simulations revealed that B7 formed stable binding modes with PI3Kα and HDAC6/8. Although rapid systemic clearance currently limits its in vivo application, the potent cellular efficacy of B7 highlights its utility as a dual PI3K/HDAC lead compound, providing a distinct chemical scaffold for further structural optimization.

Keywords:  Cervical cancer; PI3Kα/HDAC6/8 inhibitor; Thienopyrimidine derivatives

DOI:  https://doi.org/10.1016/j.ejmech.2026.119315
Parasitol Int. 2026 Sep 11. pii: S1383-5769(26)00161-3. [Epub ahead of print] 103390

Stage-specific expression and localization of ETRAMP4 during gametocyte development in the malaria parasite Plasmodium falciparum.

Hideyuki Iriko, Ayaka Omoda, Hashida Aoi, Mayumi Tachibana, Tomoko Ishino, Hitoshi Otsuki, Takafumi Tsuboi.

  The early transcribed membrane protein 4 (ETRAMP4) is one of 14 predicted members of the ETRAMP family in the malaria parasite Plasmodium. All characterized ETRAMP proteins localize to the parasitophorous vacuole membrane (PVM) and associated membranous structures during the early stages of parasite infection of erythrocytes; and are thought to participate in host-parasite material transport, which is critical for parasite development. In this study, we investigated the stage-specific expression and subcellular localization of ETRAMP4 during the asexual and gametocyte intraerythrocytic stages. Indirect immunofluorescence assays revealed that ETRAMP4 is prominently detected in immature stage I and II gametocytes; whereas no detectable signal was observed in stage III to V gametocytes or in asexual blood-stage parasites under our experimental conditions. Immunoelectron microscopy demonstrated that ETRAMP4 predominantly localizes to the PVM and PVM-derived membranous structures extending into the host erythrocyte cytoplasm, suggesting a potential role in membrane dynamics during early gametocyte development.

Keywords:  Early transcribed membrane protein 4 (ETRAMP4); Gametocyte; Immunoelectron microscopy; Parasitophorous vacuole membrane; Plasmodium falciparum; Stage-specific expression

DOI:  https://doi.org/10.1016/j.parint.2026.103390