Effect of deletion of gra17 and gra23 genes on the growth, virulence, and immunogenicity of type II Toxoplasma gondii

Li, Tingting; Wang, Jin‐Lei; Liang, Qin‐Li; Sun, Li-Xiu; Zhang, Hai-Sheng; Zhang, Zhiwei; Zhu, Xing‐Quan; Elsheikha, Hany M.

doi:10.1007/s00436-020-06815-z

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…Although the GRA proteins appear to act synergistically, it remains unclear if they have separate or overlapping functions. Studies in mice have revealed that GRA17-mediated PVM permeability is important for the growth of tachyzoites (the rapidly growing life stage of T. gondii) and virulence in mice, whereas both GRA17 and GRA23 are important for the viability of the T. gondii life stage inside cysts (Gold et al, 2015;Paredes-Santos et al, 2019;Li et al, 2020). Interestingly, GRA17 and GRA23 show predicted structural similarity to Plasmodium EXP2, the pore-forming component of the Plasmodium translocon of exported proteins (PTEX) that is also secreted from dense granules.…”

Section: Nutrient Transfer Across the Pvmmentioning

confidence: 99%

How Malaria Parasites Acquire Nutrients From Their Host

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Koning-Ward

2021

Front. Cell Dev. Biol.

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Plasmodium parasites responsible for the disease malaria reside within erythrocytes. Inside this niche host cell, parasites internalize and digest host hemoglobin to source amino acids required for protein production. However, hemoglobin does not contain isoleucine, an amino acid essential for Plasmodium growth, and the parasite cannot synthesize it de novo. The parasite is also more metabolically active than its host cell, and the rate at which some nutrients are consumed exceeds the rate at which they can be taken up by erythrocyte transporters. To overcome these constraints, Plasmodium parasites increase the permeability of the erythrocyte membrane to isoleucine and other low-molecular-weight solutes it requires for growth by forming new permeation pathways (NPPs). In addition to the erythrocyte membrane, host nutrients also need to cross the encasing parasitophorous vacuole membrane (PVM) and the parasite plasma membrane to access the parasite. This review outlines recent advances that have been made in identifying the molecular constituents of the NPPs, the PVM nutrient channel, and the endocytic apparatus that transports host hemoglobin and identifies key knowledge gaps that remain. Importantly, blocking the ability of Plasmodium to source essential nutrients is lethal to the parasite, and thus, components of these key pathways represent potential antimalaria drug targets.

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Section: Nutrient Transfer Across the Pvmmentioning

confidence: 99%

How Malaria Parasites Acquire Nutrients From Their Host

Counihan

Modak

Koning-Ward

2021

Front. Cell Dev. Biol.

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“…Some GRAs contribute to parasite virulence in mice ( 11 , 22 , 38 , 57 , 59 , 60 ). This effect was also observed in TGME49_266410 in the present study.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of 15 Novel Dense Granule Proteins in Toxoplasma gondii Using the CRISPR-Cas9 System

et al. 2023

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“…For example, GRA23 and GRA17 control the delivery of small metabolites to the PV and promotes the structural stability of the PV (110). More recently, GRA17 and GRA23 have been shown to mediate the growth, virulence, cyst burden, and immunogenicity of the type II PRU strain (111). GRA39 contributes to parasite virulence and tissue cyst burden (108).…”

Section: What Mediates the Course Of A Persistent Brain Infection?mentioning

confidence: 99%

Epidemiology, Pathophysiology, Diagnosis, and Management of Cerebral Toxoplasmosis

2020

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SUMMARY Toxoplasma gondii is known to infect a considerable number of mammalian and avian species and a substantial proportion of the world’s human population. The parasite has an impressive ability to disseminate within the host’s body and employs various tactics to overcome the highly regulatory blood-brain barrier and reside in the brain. In healthy individuals, T. gondii infection is largely tolerated without any obvious ill effects. However, primary infection in immunosuppressed patients can result in acute cerebral or systemic disease, and reactivation of latent tissue cysts can lead to a deadly outcome. It is imperative that treatment of life-threatening toxoplasmic encephalitis is timely and effective. Several therapeutic and prophylactic regimens have been used in clinical practice. Current approaches can control infection caused by the invasive and highly proliferative tachyzoites but cannot eliminate the dormant tissue cysts. Adverse events and other limitations are associated with the standard pyrimethamine-based therapy, and effective vaccines are unavailable. In this review, the epidemiology, economic impact, pathophysiology, diagnosis, and management of cerebral toxoplasmosis are discussed, and critical areas for future research are highlighted.

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Effect of deletion of gra17 and gra23 genes on the growth, virulence, and immunogenicity of type II Toxoplasma gondii

Cited by 9 publications

References 37 publications

How Malaria Parasites Acquire Nutrients From Their Host

How Malaria Parasites Acquire Nutrients From Their Host

Functional Characterization of 15 Novel Dense Granule Proteins in Toxoplasma gondii Using the CRISPR-Cas9 System

Epidemiology, Pathophysiology, Diagnosis, and Management of Cerebral Toxoplasmosis

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