Researchers provide new insight into toxoplasmosis infection
UK and Swiss researchers have shed new light on the way in which the parasite that causes toxoplasmosis invades human cells. Their findings, reported in the latest edition of the EMBO Journal, could pave the way for new therapeutic strategies to fight the disease. Toxoplasmosis is caused by a parasitic protozoan, Toxoplasma gondii, and is a disease carried primarily by cats and other mammalian species. Humans can catch the disease from eating undercooked infected meat, particularly lamb and pork, or from contact with cat faeces. The organism may also be present in some unpasteurised dairy products, such as goat's cheese, and can even be found in soil. Although the incidence of toxoplasmosis among humans has probably not changed significantly over the years, awareness and concern about the disease has increased. It has been estimated that about 50% of the world's human population has been infected with Toxoplasma, and harbours the clinically inapparent cyst form. No vaccine is as yet available to prevent either Toxoplasma infection or toxoplasmosis in cats, humans, or other species. The risk of infection is a cause of concern for mothers-to-be, since the disease can lead to birth defects in infants. In people with a weakened immune system, such as HIV patients, the disease can cause a variety of symptoms, including enlargement of the lymph nodes, ocular and central nervous-system disturbances, respiratory disease, and heart disease. In these patients, relapses of the disease are common, and the mortality rate is high. Now researchers from Imperial College London and the University of Geneva have uncovered new information about the atomic structure of a key protein called TgMIC1, which is released onto the surface of the parasite just before it invades host cells in the human body. This is one of first micronemal proteins (MICs) to be discovered in T. gondii, which functions in cell adhesion. Recent studies have shown that a purified TgMIC1 subcomplex is a potent antigen and acts as an effective vaccine in the mouse model. The researchers found that the protein binds to certain sugars on the surface of the host cell, which helps the parasite stick and then enter human cells. Using a novel carbohydrate microarray, they were able to able to identify for the first time the precise sugars to which the parasite protein binds. Combining NMR spectroscopy and cellular studies allowed the researchers to then characterise the behaviour and interactions of the parasite protein and host cell sugars. This has provided a much-needed detailed picture of how the Toxoplasma gondii attacks its host. 'Understanding the fundamental, atomic-level detail of how diseases like toxoplasmosis pick out and invade host cells in the human body is vital if we want to fight these diseases effectively,' said Professor Steve Matthews from Imperial College London's Division of Molecular Biosciences, one of the paper's authors. 'Now that we understand that it's a key interaction between a protein on the parasite's surface and sugars on the human cell which lead to the cell's invasion, there is potential to develop therapeutics that are targeted at disrupting this mechanism, therefore thwarting infection,' he added.
Switzerland, United Kingdom