4.7 Article

Metabolic flexibilities and vulnerabilities in the pentose phosphate pathway of the zoonotic pathogen Toxoplasma gondii

期刊

PLOS PATHOGENS
卷 18, 期 9, 页码 -

出版社

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1010864

关键词

-

资金

  1. National Natural Science Foundation of China [32002305]
  2. Laboratory for Lingnan Modern Agriculture Project [NT2021007]
  3. Natural Science Foundation of Guangdong Province [2022A1515011104]
  4. Sino-German Center for Research Promotion [M-0074]
  5. Science and Technology Program of Guangzhou, China [202201010500]
  6. 111 Project [D20008]
  7. Innovation Team Project of Guangdong University [2019KCXTD001]

向作者/读者索取更多资源

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.
Metabolic pathways underpin the growth and virulence of intracellular parasites and are therefore promising antiparasitic targets. The pentose phosphate pathway (PPP) is vital in most organisms, providing a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose sugar for nucleotide synthesis; however, it has not yet been studied in Toxoplasma gondii, a widespread intracellular pathogen and a model protozoan organism. Herein, we show that T. gondii has a functional PPP distributed in the cytoplasm and nucleus of its acutely-infectious tachyzoite stage. We produced eight parasite mutants disrupting seven enzymes of the PPP in T. gondii. Our data show that of the seven PPP proteins, the two glucose-6-phosphate dehydrogenases (TgG6PDH1, TgG6PDH2), one of the two 6-phosphogluconate dehydrogenases (Tg6PGDH1), ribulose-5-phosphate epimerase (TgRuPE) and transaldolase (TgTAL) are dispensable in vitro as well as in vivo, disclosing substantial metabolic plasticity in T. gondii. Among these, TgG6PDH2 plays a vital role in defense against oxidative stress by the pathogen. Further, we show that Tg6PGDH2 and ribulose-5-phosphate isomerase (TgRPI) are critical for tachyzoite growth. The depletion of TgRPI impairs the flux of glucose in central carbon pathways, and causes decreased expression of ribosomal, microneme and rhoptry proteins. In summary, our results demonstrate the physiological need of the PPP in T. gondii while unraveling metabolic flexibility and antiparasitic targets.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Parasitology

Detection of unusual Cryptosporidium parvum subtype in patients with gastrointestinal cancer in Egypt

Mona I. Ali, Wegdan M. Abd El Wahab, Ahmed Hassan, Una Ryan, Lihua Xiao, Waleed M. Arafa, Doaa A. Hamdy

Summary: This study aimed to assess the occurrence and genetic characteristics of Cryptosporidium spp. in patients with gastrointestinal cancer in Egypt. The study found that only 7% of GI cancer patients were positive for Cryptosporidium, and male sex and younger age were major risk factors for infection.

PARASITOLOGY RESEARCH (2023)

Editorial Material Public, Environmental & Occupational Health

First human infection with Cryptosporidium erinacei XIIIb - a case report from Denmark

Tine Graakjaer Larsen, Jonas Kahler, Marianne Lebbad, Huma Aftab, Luise Mueller, Steen Ethelberg, Lihua Xiao, Christen Rune Stensvold

TRAVEL MEDICINE AND INFECTIOUS DISEASE (2023)

Article Microbiology

Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins

Xianghui Liang, Xiaoyuan Chen, Junqiong Zhai, Xiaobing Li, Xu Zhang, Zhipeng Zhang, Ping Zhang, Xiao Wang, Xinyuan Cui, Hai Wang, Niu Zhou, Zu-Jin Chen, Renwei Su, Fuqing Zhou, Edward C. Holmes, David M. Irwin, Rui-Ai Chen, Qian He, Ya-Jiang Wu, Chen Wang, Xue-Qing Du, Shi-Ming Peng, Wei-Jun Xie, Fen Shan, Wan-Ping Li, Jun-Wei Dai, Xuejuan Shen, Yaoyu Feng, Lihua Xiao, Wu Chen, Yongyi Shen

Summary: Using CT scans, histological examination, blood gas tests, and transcriptome analysis, this study reveals the pathogenicity and tissue tropism of SARSr-CoV-2 in Malayan pangolins. The virus infects multiple organs, with the lungs being the major target. The study also provides initial evidence for vertical transmission of the virus in pangolin fetuses.

PLOS PATHOGENS (2023)

Article Microbiology

The Mitochondrial Pyruvate Carrier Coupling Glycolysis and the Tricarboxylic Acid Cycle Is Required for the Asexual Reproduction of Toxoplasma gondii

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

Mitochondrial ADP/ATP Carrier 1 Is Important for the Growth of Toxoplasma Tachyzoites

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 Public, Environmental & Occupational Health

High zoonotic potential and heavy environmental burden of Cryptosporidium spp. and Enterocytozoon bieneusi in farmed and pet African pygmy hedgehogs (Atelerix albiventris)

Xinan Meng, Wenlun Chu, Yongping Tang, Weijian Wang, Yuxin Chen, Na Li, Yaoyu Feng, Lihua Xiao, Yaqiong Guo

Summary: This study investigated the prevalence and zoonotic potential of Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis in farmed and pet African pygmy hedgehogs in southern China. The results showed that Cryptosporidium spp. and E. bieneusi were common in these hedgehogs, indicating a potential risk for zoonotic transmission. The detection rates were influenced by living conditions and hygiene practices. Preventive measures should be taken to reduce the risk of transmission and environmental contamination.

ONE HEALTH (2023)

Article Biology

Synthesis vs. salvage of ester- and ether-linked phosphatidylethanolamine in the intracellular protozoan pathogen Toxoplasma gondii

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

AP2XII-1 is a negative regulator of merogony and presexual commitment in Toxoplasma gondii

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.
Article Microbiology

Exploring genetic variability of Giardia duodenalis and Enterocytozoon bieneusi in raw vegetables and fruits: implications for food safety and public health in Mozambique

Catia Salamandane, Maria Luisa Lobo, Sonia Afonso, Lihua Xiao, Olga Matos

Summary: This study assessed the genetic pattern of Giardia duodenalis and Enterocytozoon bieneusi in vegetables and fruits sold in Maputo markets, Mozambique, and determined their public health importance. The results showed that 2.8% and 1.3% of the monitored samples were positive for G. duodenalis and E. bieneusi, respectively. Additionally, these microorganisms were found and characterized for the first time in horticultural products in Maputo markets.

FRONTIERS IN MICROBIOLOGY (2023)

Article Biotechnology & Applied Microbiology

Role of 6-phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine

Qinghong Guo, Xuefang Guo, Nuo Ji, Bang Shen, Xinhua Zhong, Lihua Xiao, Yaoyu Feng, Ningbo Xia

Summary: Toxoplasma gondii is a widespread pathogen that infects various warm-blooded animals, including humans, leading to significant socioeconomic and healthcare burdens. Despite the lack of an ideal toxoplasmosis vaccine, targeting key pathways in the parasite's metabolism shows promise for new antiparasitic strategies.

MICROBIAL BIOTECHNOLOGY (2023)

Article Genetics & Heredity

High subtelomeric GC content in the genome of a zoonotic Cryptosporidium species

Jiayu Li, Na Li, Dawn M. Roellig, Wentao Zhao, Yaqiong Guo, Yaoyu Feng, Lihua Xiao

Summary: The genome of Cryptosporidium canis has a higher GC content and this is mainly found in subtelomeric regions. Genes with balanced GC content encode Cryptosporidium-specific proteins that participate in host-parasite interactions. Natural selection plays a significant role in the evolution of codon usage in GC-balanced C. canis. The genome of the fox-derived isolate differs more from the mink and dog-derived isolates, suggesting the presence of a new Cryptosporidium species.

MICROBIAL GENOMICS (2023)

Article Biochemistry & Molecular Biology

Apically-located P4-ATPase1-Lem1 complex internalizes phosphatidylserine and regulates motility-dependent invasion and egress in Toxoplasma gondii

Kai Chen, Xiyu Huang, Ute Distler, Stefan Tenzer, Ozlem Guenay-Esiyok, Nishith Gupta

Summary: This study reveals the working mechanism and importance of PtdSer flipping during the lytic cycle of Toxoplasma gondii. P4-ATPase1 and TgLem1 work together to translocate PtdSer across the plasma membrane, and their interaction is crucial for the reproduction, motility, egress, and invasion of tachyzoites. The P4-ATPase1-Lem1 heterocomplex could be a potential drug target in T. gondii.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2023)

暂无数据