Article
Microbiology
Xiao-Nan Zheng, Jin-Lei Wang, Hany M. M. Elsheikha, Meng Wang, Zhi-Wei Zhang, Li-Xiu Sun, Xin-Cheng Wang, Xing-Quan Zhu, Ting-Ting Li
Summary: The analysis of the subcellular localization and function of dense granule proteins is crucial for understanding the pathogenesis of Toxoplasma gondii infection. This study identified 15 novel GRAs and determined their localization and functions in different life cycle stages and strains of T. gondii. Deletion of TGME49_266410 and TGME49_315910 significantly affected parasite growth and virulence, demonstrating their importance in T. gondii pathogenicity.
MICROBIOLOGY SPECTRUM
(2023)
Review
Immunology
Chanjin Yoon, Yu Seong Ham, Woo Jin Gil, Chul-Su Yang
Summary: This review article provides an overview of the activation and specific role of the NLRP3 inflammasome in Toxoplasma gondii infection. It points out that the role of NLRP3 inflammasome in T. gondii infection is still uncertain and the mechanisms of its activation in different cell types are still unknown.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Tadakimi Tomita, Debanjan Mukhopadhyay, Bing Han, Rama Yakubu, Vincent Tu, Joshua Mayoral, Tatsuki Sugi, Yanfen Ma, Jeroen P. J. Saeij, Louis M. Weiss
Summary: The study reveals that the cyst matrix protein MAG1 functions as a secreted immunomodulatory effector, regulating parasite virulence and dissemination by suppressing inflammasome activation. The balance between GRA15-induced inflammasome activation and MAG1-mediated suppression plays a crucial role in host-parasite interactions and the establishment of chronic infection.
Review
Biology
Tadakimi Tomita, Rebekah B. Guevara, Lamisha M. Shah, Andrews Y. Afrifa, Louis M. Weiss
Summary: Toxoplasma gondii is an obligate intracellular parasite that chronically infects a third of humans. Recent advancements in T. gondii research have revealed a plethora of parasite-secreted proteins that suppress as well as activate immune responses. The parasite has developed various mechanisms to suppress host immune responses and ensure its own survival and transmission.
Article
Microbiology
Nicholas Rinkenberger, Alex Rosenberg, Joshua B. Radke, Jaya Bhushan, Tadakimi Tomita, Louis M. Weiss, L. David Sibley
Summary: Autophagy plays a role in innate immunity by targeting intracellular pathogens for elimination. Genetic differences in LC3 recruitment between resistant and susceptible strains of Toxoplasma gondii were investigated, revealing a new mechanism for cell-autonomous restriction of intracellular pathogens.
Review
Microbiology
Michael B. Griffith, Camille S. Pearce, Aoife T. Heaslip
Summary: This review provides an overview of the current understanding and outstanding questions regarding the biogenesis, trafficking, and regulation of secretion of dense granules in Toxoplasma gondii. It also highlights the functions of dense granule proteins upon secretion, with a focus on recently identified proteins.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Biology
Juliana A. Portes, Rossiane C. Vommaro, Lucio Ayres Caldas, Erica S. Martins-Duarte
Summary: Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis and can infect up to 50% of the world population. It invades host cells and forms a parasitophorous vacuole (PV) to ensure its survival. Secretion of proteins from specialized organelles allows T. gondii to modify the PV environment and manipulate host cell functions, enabling it to access nutrients and remain undetected. This review focuses on the formation of PV and its differentiation into tissue cyst, with emphasis on strategies for nutrient acquisition and host cell modification proteins.
Article
Biology
Daniel N. A. Tagoe, Allison A. Drozda, Julia A. Falco, Tyler J. Bechtel, Eranthie Weerapana, Marc-Jan Gubbels
Summary: The invasion process of apicomplexan parasites like Toxoplasma gondii into host cells is facilitated by the sequential exocytosis of microneme, rhoptry, and dense granule organelles. The DOC2 protein family plays a key role in this exocytosis process and Ca2+ helps engage C2 domains with lipids, membranes, and proteins for vesicular trafficking and membrane fusion. Ferlins are important for microneme and rhoptry exocytosis in T. gondii, with ferlins facilitating membrane fusion without SNAREs, especially in apicomplexan parasites.
Review
Biochemistry & Molecular Biology
Michael W. Panas, John C. Boothroyd
Summary: Toxoplasma gondii relies on exporting effector proteins to interfere with host cellular processes, including transcription, immune responses, and cell cycle. This coordinated action of a large collection of effectors is both elegant and complex, allowing the parasite to control the host cell effectively.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Joshua Mayoral, Rebekah B. Guevara, Yolanda Rivera-Cuevas, Vincent Tu, Tadakimi Tomita, Julia D. Romano, Leslie Gunther-Cummins, Simone Sidoli, Isabelle Coppens, Vernon B. Carruthers, Louis M. Weiss
Summary: This study investigates the interaction between the secreted protein GRA64 of Toxoplasma gondii and host endosomal sorting complexes required for transport (ESCRT), and reveals the important role of GRA64 in tissue cyst formation. This study lays the foundation for further understanding the mechanics and consequences of host ESCRT-parasite protein interactions.
Article
Immunology
Min Chen, Pei Yang, Zixuan Xin, Jiating Chen, Weihao Zou, Lijuan Zhou, Lili Yang, Jiao Peng, Hongjuan Peng
Summary: Toxoplasma gondii is a pathogen causing toxoplasmosis and has similarities with immunotherapy for cancers. The knockout of GRA5 gene in T. gondii resulted in an avirulent strain that stimulated immune responses. ME49 & UDelta;gra5 vaccination provided protection against T. gondii infection and breast cancer by boosting anti-tumor responses. The vaccine upregulated Th1 cytokines and tumor-infiltrating T cells, and increased the number of immune cells in the spleen.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Esther Rajendran, Morgan Clark, Cibelly Goulart, Birte Steinhofel, Erick T. Tjhin, Simon Gross, Nicholas C. Smith, Kiaran Kirk, Giel G. van Dooren
Summary: This study reveals the regulation mechanism by which the apicomplexan parasite senses and responds to changes in arginine availability, showing that the expression of TgApiAT1 is modulated by the arginine concentration in the environment. The regulation is post-transcriptional and mediated by an upstream open reading frame (uORF) encoded peptide, highlighting the parasite's ability to adapt to different nutrient environments through modulating arginine uptake.
Article
Biochemical Research Methods
Rosalba Cruz-Miron, Carlos J. Ramirez-Flores, Noe Lagunas-Cortes, Monica Mondragon-Castelan, Emmanuel Rios-Castro, Sirenia Gonzalez-Pozos, M. Magdalena Aguirre-Garcia, Ricardo Mondragon-Flores
Summary: Toxoplasma gondii, a successful intracellular parasite, relies on a complex machinery located in the pellicle for its dynamic functions. The protein composition of the pellicle is not well understood, but recent research identified new SRS proteins that could potentially be targets for designing immunoprotective strategies or drugs against Toxoplasma. Further studies are needed to explore the roles of these proteins in host immune response activation and invasion mechanisms.
JOURNAL OF PROTEOMICS
(2021)
Article
Biochemistry & Molecular Biology
Heng Zhang, Yangfei Xue, Xu Yang, Jing Liu, Qun Liu
Summary: Toxoplasma gondii UBL-UBA shuttle proteins regulate crucial cellular processes, with ROP18 mislocalization potentially representing an abnormal homeostasis due to shuttle protein mutation.
Review
Immunology
Eva-Maria Frickel, Christopher A. Hunter
Summary: Toxoplasma gondii is a valuable experimental system for studying how the immune system deals with intracellular infections, particularly in relation to the cytokine IFN-gamma and the strategies pathogens use to evade antimicrobial responses. Its genetic tractability allows for research on the basis of latency and continues to provide insights into host-pathogen interactions.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Xiaohan Liang, Jianmin Cui, Xuke Yang, Ningbo Xia, Yaqiong Li, Junlong Zhao, Nishith Gupta, Bang Shen
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Parasitology
Yaqiong Li, Yue Zhang, Ningbo Xia, Taifang Zhou, Bang Shen
Summary: The concept of using pathogens as drugs has been recognized for over a century and has gained recent research attention for fighting diseases such as immune disorders. Studies have shown that Toxoplasma gondii mutants lacking two lactate dehydrogenases have high antitumor activity, inhibiting tumor growth in mouse models. Chronic Toxoplasma infection also demonstrates antitumor activity, and pre-existing chronic infections do not affect the efficacy of the mutant in repressing tumor growth.
PARASITOLOGY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Congcong Lyu, Xuke Yang, Jichao Yang, Lun Hou, Yanqin Zhou, Junlong Zhao, Bang Shen
Summary: This study identified a starch synthase required for amylopectin synthesis in Toxoplasma gondii, which plays a critical role in parasite growth, development, and virulence. Disrupting this enzyme may impact the pathogen's proliferation and ability to move between different life cycle stages, highlighting a potential drawback in using such mutants as vaccine candidates.
Article
Microbiology
Xuke Yang, Xiaoyan Yin, Jiaojiao Liu, Zhipeng Niu, Jichao Yang, Bang Shen
Summary: PPi-PFK plays a crucial role in glycolysis, coordinating anabolism and catabolism in parasites by maintaining pyrophosphate homeostasis and maximizing nutrient utilization efficiency. Its physiological significance in Toxoplasma and other organisms has been highlighted, suggesting a potential drug target for combating toxoplasmosis.
Article
Microbiology
Jingwen Zhang, Fuqiang Fan, Lihong Zhang, Bang Shen
Summary: The transcription factor TgAP2X-4 plays a crucial role in the growth and life cycle progression of Toxoplasma gondii. It regulates the expression of cell cycle-regulated genes and genes involved in the development of chronic infection. Inactivation of TgAP2X-4 severely impairs parasite growth, attenuates virulence, and prevents the formation of chronic infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Ningbo Xia, Xuefang Guo, Qinghong Guo, Nishith Gupta, Nuo Ji, Bang Shen, Lihua Xiao, Yaoyu Feng
Summary: This study reveals the importance of the pentose phosphate pathway (PPP) in the growth and virulence of the intracellular parasite Toxoplasma gondii, and uncovers the metabolic flexibility and potential antiparasitic targets of the parasite.
Article
Microbiology
Jianmin Cui, Xuke Yang, Jichao Yang, Ruilian Jia, Yaoyu Feng, Bang Shen
Summary: Toxoplasma gondii relies on phosphate transporters TgPiT, TgPT2, and TgmPT to acquire necessary nutrients for survival. TgPT2 is essential for parasite growth and its depletion impairs motility, invasion, and growth of the parasites. Toxoplasma is also capable of scavenging host ATP, indicating its ability to obtain energy from the environment.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Yongle Song, Longjiao Li, Xinyu Mo, Ming Pan, Bang Shen, Rui Fang, Min Hu, Junlong Zhao, Yanqin Zhou
Summary: Toxoplasma gondii is a pathogen that poses a threat to human and animal health. Calcium ions play a crucial role in regulating important biological processes in the parasite. This study explored the function of calmodulin (CaM), a calcium-binding protein, in T. gondii and identified more than 300 interacting proteins using BioID technology.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Zhipeng Niu, Shu Ye, Jiaojiao Liu, Mengyu Lyu, Lilan Xue, Muxiao Li, Congcong Lyu, Junlong Zhao, Bang Shen
Summary: This study investigates the physiological roles of glycolytic enzymes in the apicoplast of the parasite Toxoplasma gondii. It is found that TPI2 and GAPDH2 are critical for parasite growth, while PYK2 and PGK2 are dispensable. TPI2 provides carbon source for isoprenoid precursor synthesis, while GAPDH2 supplies reducing power for metabolic pathways in the parasite.
Article
Microbiology
Congcong Lyu, Yukun Chen, Yanan Meng, Jichao Yang, Shu Ye, Zhipeng Niu, Issam EI-Debs, Nishith Gupta, Bang Shen
Summary: Toxoplasma gondii is capable of infecting humans and animals, and its metabolic flexibility plays a crucial role in its parasitic life cycle. This study identified the mitochondrial pyruvate carrier (MPC) complex in T. gondii, which is responsible for transporting cytosolic pyruvate into the mitochondrion. The deletion of MPC subunits resulted in impaired synthesis of acetyl-CoA and reduced carbon flux through glycolysis and the tricarboxylic acid (TCA) cycle. Although disruption of MPC proteins had only a modest effect on the parasite's virulence in mice, it highlights the metabolic plasticity of T. gondii.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Jiahui Qian, Tongjie Zhao, Liyu Guo, Senyang Li, Zhengming He, Mingfeng He, Bang Shen, Rui Fang
Summary: Metabolism associated with energy production is compartmentalized in eukaryotic cells, and transporters that move metabolites across organelle membranes play key roles. In this study, researchers identified and characterized two putative ADP/ATP carriers in Toxoplasma gondii. They found that TgAAC1 functions as the mitochondrial ADP/ATP carrier and is critical for parasite growth.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biology
Bingjian Ren, Xiaohan Liang, Jos F. Brouwers, Rosalba Cruz Miron, Bang Shen, Nishith Gupta
Summary: A genetic and lipidomic investigation showed that depletion of ECT in Toxoplasma gondii disrupts PtdEtn synthesis and results in parasite death. T. gondii salvages ether-PtdEtn from its host cells. This study reveals the diverse mechanisms employed by T. gondii to produce different forms of PtdEtn.
COMMUNICATIONS BIOLOGY
(2023)
Article
Microbiology
Fuqiang Fan, Lilan Xue, Xiaoyan Yin, Nishith Gupta, Bang Shen
Summary: Transition from asexual to sexual development in Toxoplasma gondii is controlled by a novel transcription factor, TgAP2XII-1. This factor represses the presexual development in the asexual tachyzoite stage. Parasites lacking AP2XII-1 exhibit a merozoite-type transcriptional profile. This study provides insight into the sexual commitment of T. gondii and suggests a potential method for culturing presexual stages.