Toxoplasmosis infection trick revealed by scientists

Toxoplasmosis

Scientists provide new insight into how toxoplasmosis parasite invades human cells - News Release

Imperial College London news release

Under strict embargo for
1700 hours British Summer Time
Thursday 10 May 2007

Scientists have provided new insight into how the parasite which causes toxoplasmosis invades human cells, says new research published today in The EMBO Journal.

Toxoplasmosis is a parasitic disease, primarily carried by cats. It is transmitted to humans by eating undercooked meat or through contact with cat faeces. It is particularly dangerous for pregnant women, whose foetuses can be infected via the placenta, and those with a weakened immune system, such as people infected with HIV. In severe cases, toxoplasmosis can cause damage to the brain and eyes, and even death.

Now researchers from London and Geneva have determined, for the first time, the atomic structure of a key protein which is released onto the surface of the parasite just before it invades host cells in the human body. They found that the protein known as TgMIC1 binds to certain sugars on the surface of the host cell, assisting the parasite to stick to, and then enter the human cell.

Using a novel carbohydrate microarray the team were able to identify the precise sugars to which the parasite protein binds. Following this the team used a combination of NMR spectroscopy and cellular studies to characterise the behaviour and interactions of the parasite protein and host cell sugars. This means that the team have a more detailed picture than ever before of exactly how the parasite recognises and attacks host cells in the body.

Professor Steve Matthews  from Imperial College London's Division of Molecular Biosciences, one of the paper's authors, explains the significance of the research, saying: "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.

"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."

Toxoplasma gondii, the parasite that causes toxoplasmosis, is one of the world's most common parasites. Around a quarter to half of the world's population is thought to be infected, and around 1 per cent of people in the UK catch toxoplasmosis each year. In the majority of cases, those affected don't have any symptoms. But for those with weakened immune systems, and unborn babies, toxoplasmosis can cause very serious health problems.

-Ends-

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Danielle Reeves, Imperial College London Press Office,
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Notes to Editors:

1. 'Atomic resolution insight into host cell recognition by Toxoplasma gondii', The EMBO Journal, 10 May 2007.

Tharin MA Blumenschein (1), Nikolas Friedrich (2), Robert A Childs (3), Savvas Saouros (1), Elisabeth P Carpenter (1), Maria A Campanero-Rhodes (3), Peter Simpson (1), Wengang Chai (3), Theodoros Koutroukides (4), Michael J Blackman (5), Ten Feizi (3), Dominique Soldati-Favre (2) and Stephen Matthews (1).

(1) Division of Molecular Biosciences, Imperial College London, London, UK.
(2) department of Microbiology and Genetics, Faculty of Medicine, university of Geneva CMU, Geneva, Switzerland.
(3) Glycosciences Laboratory, Division of Medicine, Imperial College London, Middlesex, UK.
(4) Medical Science division, Fox Chase Cancer Centre, Philadelphia, PA, USA.
(5)Division of Parasitology, National Institute for Medical Research, London, UK.

2. About Imperial College London

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Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

With 62 Fellows of the Royal Society among our current academic staff and distinguished past members of the College including 14 Nobel Laureates and two Fields Medallists, Imperial's contribution to society has been immense. Inventions and innovations include the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of our research for the benefit of all continues today with current focuses including interdisciplinary collaborations to tackle climate change and mathematical modelling to predict and control the spread of infectious diseases.

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