The molecular biology and immune control of chronic Toxoplasma gondii infection

Zhao, Xiao-Yu; Ewald, Sarah E.

doi:10.1172/jci136226

Cited by 68 publications

(51 citation statements)

References 168 publications

(173 reference statements)

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“…Although these methods offer good sensitivity, they are limited by various constraints such as susceptibility to false positives and lack of compatibility with point-of-need applications [7]. LAMP is characterized by a streamlined protocol and exemplary detection limit of 1 copy of T. gondii DNA per reaction, but spurious ampli cation can occasionally arise and is prone to aerosol pollution [5]. RAA-LFD is to perform isothermal ampli cation of the target gene or specimen by the RAA method and then combine with LFD technology, LFD is a technology that nally realizes the visual analysis of ampli ed products.…”

Section: Discussionmentioning

confidence: 99%

“…People with normal immune function may not have typical symptoms and show recessive infection after infection with T. gondii, but pregnant women infected with T. gondii can lead to premature delivery, abortion, teratosis, stillbirth, etc., and newborn is regularly accompanied by serious eye diseases [1,4]. For humans with weakened immune function or immunode ciency, such as AIDS patients, organ transplant recipients, tumor patients, etc., infection with T. gondii can cause extreme encephalitis and even death [5,6]. Therefore, effective, rapid and accurate diagnosis is needed to improve development of treatment approaches, enhance prognosis and control dissemination.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Rapid Visual Detection of Toxoplasma Gondii by Combining Recombinase Polymerase Amplification and Lateral Flow Dipstick Coupled With CRISPR-Cas13a Fluorescence Assay

Zhao¹,

Li²,

Xue³

et al. 2021

Preprint

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Background: Toxoplasmosis caused by infecting with Toxplasma gondii is a kind of parasitic disease that prevalent all over the world and does great harm to pregnant women and newborns. Effective, rapid and accurate diagnosis T. gondii is urgently needed to prevent and treatment the toxoplasmosis. The purpose of this study was to develop a rapid visual detection assay using recombinase aided amplification (RAA) and lateral flow dipstick (LFD) coupled with CRISPR-Cas13a fluorescence, henceforth RAA-Cas13a-LFD, for detection of T. gondii.Methods: Targeting 529bp gene of T. gondii, the primers and probes for RAA-Cas13a-LFD assay were designed and screened. The reaction time of RAA-LFD-Cas13a assay was optimized, as well as the sensitivity and specificity was further validated. Finally, the diagnostic performance of T. gondii was evaluated using the RAA-Cas13a-LFD assay for clinical blood samples.Results: The RAA-Cas13a-LFD assay was performed in an incubator block at 37℃ within 2h, and the amplicons were visible through LFD for naked eye visualization. The detection limit of the developed RAA-Cas13a-LFD assay was 1×10-6 ng/μL with high specificity for T. gondii. Compared with qPCR assay, there was a consistent positive rate among the clinical blood samples. Conclusion: In this study, A rapid and visual RAA-Cas13a-LFD assay was developed. It requires no sophisticated equipment and shows promise for on-site surveillance of T. gondii.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Rapid Visual Detection of Toxoplasma Gondii by Combining Recombinase Polymerase Amplification and Lateral Flow Dipstick Coupled With CRISPR-Cas13a Fluorescence Assay

Zhao¹,

Li²,

Xue³

et al. 2021

Preprint

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“…15 Toxoplasma gondii (re)activation may associate with chorioretinitis, encephalitis, and neuropsychiatric disorders such as schizophrenia. 16 • Plasmodium falciparum can reactivate during pregnancy after years of latency. 17 • Cryptococcus neoformans is a common central nervous system pathogen and causes fatal fungal meningoencephalitis, especially in immunocompromised subjects.…”

Section: Introductionmentioning

confidence: 99%

“… 15 Toxoplasma gondii (re)activation may associate with chorioretinitis, encephalitis, and neuropsychiatric disorders such as schizophrenia. 16 …”

Section: Introductionmentioning

confidence: 99%

Human Codon Usage: The Genetic Basis of Pathogen Latency

Kanduc

2021

Global Medical Genetics

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Infectious diseases pose two main compelling issues. First, the identification of the molecular factors that allow chronic infections, that is, the often completely asymptomatic coexistence of infectious agents with the human host. Second, the definition of the mechanisms that allow the switch from pathogen dormancy to pathologic (re)activation. Furthering previous studies, the present work (1) analyzes the frequency of occurrence of synonymous codons in coding DNA, that is, codon usage, as a genetic tool that rules protein expression; (2) describes how human codon usage can inhibit protein expression of infectious agents during latency, so that pathogen genes the codon usage of which does not conform to the human codon usage cannot be translated; and (3) frames human codon usage among the front-line instruments of the innate immunity against infections. In parallel, it is shown that, while genetics can account for the molecular basis of pathogen latency, the changes of the quantitative relationship between codon frequencies and isoaccepting tRNAs during cell proliferation offer a biochemical mechanism that explains the pathogen switching to (re)activation. Immunologically, this study warns that using codon optimization methodologies can (re)activate, potentiate, and immortalize otherwise quiescent, asymptomatic pathogens, thus leading to uncontrollable pandemics.

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“…A primary infection during pregnancy may result in congenital infection causing abortion or fetal abnormalities, including hydrocephalus, intracranial calcifications and retinochoroiditis (Montoya and Liesenfeld, 2004). In the last years, ocular toxoplasmosis was identified not only following congenital infection but also in cases of postnatally acquired infections (Smith et al, 2020;Zhao and Ewald, 2020).…”

Section: Introductionmentioning

confidence: 99%

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Mévélec

Lakhrif

Dimier‐Poisson

2020

Front. Cell. Infect. Microbiol.

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Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

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The molecular biology and immune control of chronic Toxoplasma gondii infection

Cited by 68 publications

References 168 publications

A Novel Rapid Visual Detection of Toxoplasma Gondii by Combining Recombinase Polymerase Amplification and Lateral Flow Dipstick Coupled With CRISPR-Cas13a Fluorescence Assay

A Novel Rapid Visual Detection of Toxoplasma Gondii by Combining Recombinase Polymerase Amplification and Lateral Flow Dipstick Coupled With CRISPR-Cas13a Fluorescence Assay

Human Codon Usage: The Genetic Basis of Pathogen Latency

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

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