Tag: Toxoplasma gondii

Cat-borne Toxoplasma Gondii Linked to Frailty in the Elderly

Photo by FOX: https://www.pexels.com/photo/brown-tabby-cat-scratching-head-1265613/

Toxoplasma gondii, a common, cat-borne parasite already associated with risk-taking behaviour and mental illness in humans may also contribute to exhaustion, loss of muscle mass, and other signs of frailty in older adults, suggests a study published in the Journal of Gerontology: Medical Science.

The research, by an international team of scientists including University of Colorado Boulder, University of Maryland School of Medicine and the University of A Coruña in Spain, is the latest to explore how the tiny, single-celled organism T. gondii could have big impacts on human health.

“We often think of T. gondii infection as relatively asymptomatic, but this study highlights that for some people it may have significant health consequences later on,” said co-author Christopher Lowry, a professor at CU Boulder.

Some 11%–15% of people in the US have been infected with T. gondii at some point and rates tend to be far higher in older individuals. In some countries, more than 65% have been infected. Once infected, people can unknowingly harbour the parasite for life.

For the study, the team examined the blood of 601 Spanish and Portuguese adults over 65, along with measures of a common geriatric syndrome known as frailty – which includes unintentional weight loss, tiredeness, loss of cognitive sharpness and other indications of declining health.

A whopping 67% of study subjects were “seropositive” showing markers in their blood of a latent infection.

The researchers did not, as they originally hypothesized, find an association between any infection to T. gondii and frailty. But they did find that, among those infected, those with higher “serointensity” or a higher concentration of antibodies to the parasite, were significantly more likely to be frail.

Higher serointensity could reflect a more virulent or widespread infection, multiple infections or recent reactivation of a latent infection, the authors said.

“This paper is important because it provides, for the first time, evidence of the existence of a link between frailty in older adults and intensity of the response to T. gondii infection,” said co-author Blanca Laffon, a professor of psychobiology at the Interdisciplinary Centre of Chemistry and Biology at University of A Coruña.

How cats spread T. gondii

Wild and domestic felines are considered the definitive host of the parasite, while warm-blooded animals like birds and rodents serve as secondary hosts: When cats eat infected animals, T. gondii takes up residence and multiplies in their intestines, shedding eggs in their faeces.

People are typically infected via exposure to those eggs (via litter boxes, contaminated water or dirty vegetables) or by eating undercooked pork, lamb or other meat that’s infested.

Most people never know they’ve been infected, with only about 10% initially having brief flu-like symptoms. But T. gondii tends to linger dormant for decades, cloaked in cysts in muscle and brain tissue (specifically the emotion-processing region known as the amygdala) with some insidious impacts, mounting research suggests.

In a creepy evolutionary trick seemingly designed to benefit the parasite’s favourite host, rodents infected with T. gondii tend to lose their fear of felines, making it easier for cats to catch rats and mice. In the wild, infected chimpanzees have been shown to actually grow attracted to the smell of the urine of their feline predator, the leopard.

People who have been infected also tend to engage in risky behaviour, with research showing they tend to be more impulsive, more entrepreneurial and more likely to get in a car accident. They also have higher rates of schizophrenia, certain mood disorders, cognitive problems and are more likely to attempt suicide, according to research by Lowry and Dr Teodor Postolache, a professor in the Department of Psychiatry at University of Maryland School of Medicine and senior author on the new study.

A declining immune response?

The authors caution that the new study does not prove causation, but suggests the association should be researched.

They found that frail people with high T. gondii seropositivity also had higher levels of certain inflammatory markers, suggesting that infection with the parasite could exacerbate inflammation that already occurs with aging – aka. “inflammaging.”

Because latent T. gondii tends to hide out in muscle tissue, Postolache suspects it could also play a role in hastening sarcopenia.

Lowry’s research focuses on the impact microorganisms have on the immune system and, thus, mental health. He notes that many microbes that humans have evolved with impact health in a positive way – a theory known as the ‘Old Friends’ hypothesis. Even T. gondii may have health benefits we aren’t yet aware of, he said. But in some cases, a switch flips, and friends become enemies.

In the case of T. gondii, certain medications or immune compromising diseases like HIV or cancer can enable a latent infection to escape suppression and reactivate, with adverse effects. Even in people with healthy immune systems, Lowry notes, immune function can decline with age, potentially wakening dormant dormant T. gondii.

The researchers hope their study will inspire more research into the relationship between T. gondii and frailty, and ultimately lead to new ways of keeping the parasite from doing harm.

For now, they encourage people – especially pregnant and immunocompromised people – to take steps to avoid infection.

Tips for preventing infection:

Change litter box daily, and wash hands afterward.

Avoid eating undercooked meat.

Rinse fruits and vegetables.

If pregnant or immunocompromised:

Avoid changing the litter box if possible (T. gondii infection during pregnancy can cause serious problems to a developing foetus).

Keep cats indoors.

Avoid stray cats.

Source: University of Colorado at Boulder

New Treatment for Toxoplasmosis Could Target Parasite Cysts

Toxoplasma gondii. Source: Wikimedia CC0

Findings from a new University of Kentucky College of Medicine study published in the Journal of Biological Chemistry could lead to a new treatment for Toxoplasma gondii, the parasite that causes toxoplasmosis.

An estimated 40 million people in the US carry the parasite T. gondii, according to the Centers for Disease Control and Prevention, but most are asymptomatic because the immune system usually keeps the parasite from causing illness. However, for women newly infected during pregnancy and anyone with a compromised immune system, toxoplasmosis can cause severe illness or even death.

In individuals with severe toxoplasmosis, cyst version of the parasite may be present within brain and muscle tissue. These cysts are responsible for causing serious disease, especially in people who are immunocompromised. While there are FDA-approved drugs to treat the symptoms of toxoplasmosis, no current therapeutics target the cyst form of the parasite.

The labs of Matthew Gentry, PhD, and Craig Vander Kooi, PhD, at UKCM and Zhong-Yin Zhang, PhD, at the Purdue Institute for Drug Discovery, collaborated to develop a drug that targets the cyst form of the parasite.

In previous research, Dr Gentry identified an enzyme in T. gondii called TgLaforin, which he hypothesised was critical in allowing the parasite to access energy from a carbohydrate storage molecule. The team developed a new drug that inhibits TgLaforin with the goal of preventing enzymes from accessing and providing energy to the parasite.

The new discovery was made possible thanks to the multidisciplinary collaboration of experts from the four labs, said Dr Gentry.

Robert Murphy, PhD, a member of the Gentry and Sinai labs, conducted initial experiments that characterised TgLaforin and provided a baseline for understanding the enzyme’s function.

Tiantian Chen, a graduate student in Vander Kooi’s lab, generated models of TgLaforin using a new program called AlphaFold2, an AI algorithm that provides valuable insights into research. Chen generated models that provided a picture of the enzyme that demonstrated TgLaforin was a unique and possible drug target.

Jianping Lin, PhD, a postdoc in Dr Zhang’s lab, then used information generated by Dr Murphy and Chen in combination with novel techniques in chemistry to generate the first version of a future anti-Toxoplasma drug.

“I was excited to find that the drug was effective against TgLaforin in test tubes and that it prevented TgLaforin from performing its normal activity against a variety of substrates, including carbohydrates,” said Dr Murphy.

The labs will next test the drug on parasites, and try to increase its potency and selectivity and adapt its chemical properties to allow for animal studies.

“This study is a great example of what Provost DiPaola consistently promotes regarding transdisciplinary research,” Dr Gentry said. “This work was a true team effort and it is very exciting to see where we take it next.”

Source: University of Kentucky College of Medicine

Treating Cancer with the Toxoplasma Gondii Parasite

Source: National Cancer Institute on Unsplash

Scientists have discovered that Toxoplasma gondii, a parasite known to cause illness in pregnant women and immunocompromised patients, could potentially enhance the treatment of various types of tumours.

The parasite Toxoplasma gondii is a single-celled opportunistic protozoan capable of infecting a broad range of warm-blooded animals and has been reported in nearly one-third of the world’s human population. It has a number of health effects, including a strong link to schizophrenia and has even been associated with increased suicide attempts in mothers.

While many treatments have been able to treat tumours and prolong the lives of patients, there is a need to further enhance these. In the study, published in the Journal for ImmunoTherapy Cancer, scientists found that the commonly found parasite  is able to sensitise ‘cold’  tumours, that is, tumours unlikely to trigger a strong immune response, to immune checkpoint blockade therapy.

The researchers believe that this finding could have broader therapeutic implications for many types of cancers.

T. gondii has to live inside the cells of its host and secretes numerous proteins to counter the host’s immune defences and to facilitate their own invasion and colonisation of the host cells. The researchers first built a T. gondii mutant strain with limited growth and disease-causing ability, but which is also able to manipulate the host immune system.

By directly injecting this mutant parasite into solid tumours, it induces inflammatory responses in those tumours and even in tumours located in a distant location in the mouse body. The researchers further demonstrated that this treatment approach has made tumours more responsive to treatment with immune checkpoint inhibitors.

This dual treatment significantly extended the survival of mice and reduced tumour growth in mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma.

Dr Hany Elsheikha, Associate Professor in the School of Veterinary Medicine and Science at the University of Nottingham, and one of the lead authors of the study, said: “The use of a mutant version of Toxoplasma gondii in the treatment of certain tumours in mice models has been previously reported. What makes this study different is the confirmation that intratumoural injection with mutant Toxoplasma gondii strain boosts antitumour immunity and the effectiveness of checkpoint inhibition therapy.

“These are significant findings and are relevant to future tumour therapy. The marked reduction in tumour size and the significant improvement in the survival of mice that received this novel combinational therapy is promising but should be interpreted with caution as further research is needed.”

Source: University of Nottingham