Written by | Nagashi
<h1>Abstract: It is estimated that more than 30% of humans worldwide are infected with Toxoplasma gondii, and Toxoplasma gondii infection poses a significant threat to immunocompromised people and pregnant women. There are also studies that suggest that Toxoplasma gondii infection changes host behavior, making it more eager to explore and take risks. A new study used CRISPR gene editing technology to build a mutant strain of Toxoplasma gondii that can act as a vaccine to block the spread of toxoplasma gondii from cats to humans. </h1>
Up to 30% of humans are infected with Toxoplasma gondii
Toxoplasma gondii is an intestinal coccidiosis of felines, discovered in 1908 by French scholars Nicollle and Manceaux in the hepatosplenome of the Gangdiss toe rat in North Africa.
Toxoplasma gondii is widely distributed all over the world, people and many animals can be infected, with the increase of the cat population, nearly one-third of the world's population is infected, The positive infection rate in China is 5%-20%, and in some areas up to more than 30%.
Toxoplasma gondii has a complex life cycle, consisting of both asexual and asexual stages. Although the parasite is capable of infecting many mammals, it can only complete its life cycle in felines, including domestic cats. That is, with the exception of the final host, Toxoplasma gondii can only reproduce asexually in other animals and cannot spread its offspring to the outside world.
Potential harm of Toxoplasma gondii infection
Toxoplasma gondii is an important opportunistic protozoan, and from the 1920s onwards, doctors began to recognize that if a woman is infected with Toxoplasma gondii during pregnancy, it can cause the baby to get sick and, in some cases, to blindness, mental retardation, and even severe brain damage or death.
Toxoplasma gondii is also a major threat to immunocompromised people: at the beginning of the AIDS epidemic, scientists had not yet developed effective antiretroviral drugs, and many AIDS patients suffered from dementia in the late stages of toxoplasmosis infection.
Some studies suggest that Toxoplasma gondii infections can potentially influence human behavior and even the culture of the world. For example, in the eight games in the knockout stage of the 2010 World Cup in South Africa, all countries with high rates of Toxoplasma gondii infection won.
Fortunately, healthy children and adults usually have the same symptoms as the ordinary flu in the early stages of infection with Toxoplasma gondii, but after the patient resists the invasion of Toxoplasma gondii, Toxoplasma gondii is not completely eliminated and may also lurk in brain cells.
Toxoplasma gondii is able to lurk in the brain and exercise mind control
Early studies have found that Toxoplasma gondii has a strange "mind control" ability over rodents (mice, rabbits, etc.), and once infected with this brain parasite, the brains and behaviors of mice are greatly affected, and they seem to be no longer afraid of cats and become more easily eaten, so that cats will also be more infected with Toxoplasma gondii.
It can be said that this parasite is quite "smart" and can manipulate the behavior of infected people through "mind control" to achieve the purpose of reproduction. Some studies have even linked human infection with toxoplasmosis with mental health conditions such as impulsivity/schizophrenia.
But there has been intense scientific debate about exactly how Toxoplasma gondii affects host behavior and how well it has the ability to "mind control."
In January 2020, researchers at the University of Geneva in Switzerland published the Following research paper in Cell Reports, a sub-journal of Cell Journal: Neuroinflammation-Associated Aspecific Manipulation of Mouse Predator Fear by Toxoplasma gondii.
The study showed that toxoplasma gondii infection made mice more eager to explore and eliminated fear of predators (not just cats), and found that the severity of behavioral changes was positively correlated with the number of Toxoplasma cysts in the brain, pointing to a wide range of immune-related behavioral changes.
The findings suggest that Toxoplasma gondii has found an "excellent location" that parasitizes the brain: invading the brain is enough to trigger an immune response that brings the host closer to the predator, but not enough to kill the host immediately. This can be called "a very clever strategy". In a way, Toxoplasma is a "crazy genius".
CRISPR gene editing brings the solution
About one-third of humans worldwide are infected with and carry Toxoplasma gondii, which pose a high potential risk to immunocompromised people, and toxoplasmosis infection is a potential threat for pregnant women that cannot be ignored. Therefore, the prevention and control of Toxoplasma gondii infections has great significance for human health and public health.
In December 2020, researchers at the University of Zurich in Switzerland published a research paper titled A streamlined CRISPR/Cas9 approach for fast genome editing in Toxoplasma gondii and Besnoitia besnoiti in the Journal of Biological Methods.
Using CRISPR gene editing, the research team created a toxoplasma mutant strain that exhibited poor fertilization, reduced fecundity, and prevented its oocysts from producing sporozoites. Infecting felines with this gene-edited modified Toxoplasma gondii completely prevents the spread of oocysts and sporospores after Toxoplasma gondii infection.
This suggests that this gene-edited Toxoplasma gondii can act as an attenuated vaccine that can stop the spread of Toxoplasma gondii.
What's more, the research team said that the study used electrotransfection of the Cas9 protein and chemically synthesized sgRNA, a transient component that does not contain plasmids, and that after editing the Toxoplasma gondii gene, the component is rapidly degraded, minimizing the potential risk of off-target effects.
Toxoplasma gondii has a complex life cycle and can infect almost all warm-blooded animals, including wild rodents, birds, mammals, and humans. It is estimated that more than 2 billion people worldwide are infected with and carry Toxoplasma gondii, and humans are infected mainly through three pathways: foodborne infection; maternal and infant infection; and animal-to-human infection (mainly pet cats).
The CRISPR gene-edited Toxoplasma gondii mutant strain developed in this study can effectively prevent the transmission of Toxoplasma gondii in felines, thereby cutting off the last transmission route mentioned above.
Thesis Link:
https://doi.org/10.1016/j.celrep.2019.12.019
https://www.jbmethods.org/jbm/article/view/343