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Parasite invasion uncovered on path to a vaccine

On World Health Day, 7th April 2015, the World Health Organization (WHO) is advocating for food safety. They want everyone to question: What is in your meal? Where did the ingredients come from? Were they properly - and safely - handled from every stage, from farm to plate? The parasite, Toxoplasma gondii is one of the commonest food-borne diseases requiring hospitalisation and one of the deadliest. Professor Nick Smith and Dr Robert Walker, from CBTID at James Cook University, have published two papers that are critical for their vaccine development work for this common parasite.
Parasite invasion uncovered on path to a vaccine

The research team from James Cook University and University of Zurich,

Toxoplasma gondii infects 30 per cent of the world’s people and can cause serious diseases,” Professor Smith said.  “All human infections can be traced back to infectious, egg-like structures – oocysts – that are found in cat faeces and can contaminate our food, water and soil. We aim to produce a vaccine that, when given to cats, will stop the reproduction and transmission of this dangerous parasite and reduce the incidence of toxoplasmosis.”

In their BMC Genomics published research the researchers have been able to discover what is unique about Toxoplasma in the cat compared to Toxoplasma in the many other animals it can infect.

“We discovered that the proteins and machinery that Toxoplasma uses to invade the cat is very different to those it uses in other hosts, humans and animals,” Professor Smith said.  “In our second study, we compared Toxoplasma gondii to a related parasite, Eimeria, which only lives in the intestines of chickens, and we were able to find out what proteins and enzymes are shared by these two parasites and, therefore, are important for living and reproducing in the intestine.”

By identifying proteins that are critical for the sexual development of the parasite, Toxoplasma gondii, in the cat, the research team are one step closer to discovery and development of a vaccine that can be used to stop cats transmitting this parasite into the environment and, therefore, to humans and their livestock.

“Humans can become infected with Toxoplasma by eating undercooked meat that harbours the parasite in the tissue or by eating fruit and vegetables, drinking water or handling soil that is contaminated with oocysts from cat faeces,” Dr Robert Walker said. “It is important for people to use clean water to wash their hands and fruit and vegetables and eat well-cooked meat or meat that has been previously frozen. This is especially important for pregnant women because, if a mother is infected with Toxoplasma for the first time whilst pregnant, this supremely adaptable parasite can infect the foetus.”

Toxoplasma gondii can cause serious disease (toxoplasmosis) including encephalitis, miscarriage, stillbirth, and congenital defects to mental development, hearing and sight (it is one of the most frequently identified causes of uveitis). Toxoplasmosis is one of the most damaging zoonotic diseases in the world, causing the loss of 2-8 million Disability Adjusted Life Years (DALYs). And, whilst definitive evidence for a causal link is currently lacking, infection with T. gondii is associated with schizophrenia, brain cancer and inflammatory diseases.

Toxoplasma gondii can infect any warm-blooded animal as an intermediate host but cats are its only definitive hosts; sexual reproduction of T. gondii occurs only in cats. The end-product of sexual reproduction is the oocyst. Hundreds of millions of oocysts may be shed in the faeces of a single cat and can infect a wide variety of intermediate hosts. Once infected, these hosts carry T. gondii for life in tissue cysts within brain and muscle cells, waiting to be eaten by a cat to complete the life cycle.  Thus, stopping the parasite in its tracks inside the cat will stop it entering our food chain.

The research was conducted by scientists from James Cook University.

AB Hehl, WU Basso, C Lippuner, C Ramakrishnan, M Okoniewski, RA Walker, M E Grigg, N C Smith and P Deplazes, Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes, BMC Genomics 2015, 16:66  http://www.biomedcentral.com/1471-2164/16/66

The second paper stemming out of the combined funding From Bellberry, the NIH (a EuPathDB Driving biological Discoveries Grant awarded to Professors Adrian Hehl, Peter Deplazes, Michael Grigg and Nicholas Smith) and a Swiss Government Excellence Scholarship to Dr Rob Walker has just been published in BMC Genomics:

R A Walker, PA Sharman, CM Miller, C Lippuner, M Okoniewski, RM Eichenberger, C Ramakrishnan, F  Brossier, P Deplazes, AB Hehl and NC Smith, RNA Seq analysis of the Eimeria tenella gametocyte transcriptome reveals clues about the molecular basis for sexual reproduction and oocyst biogenesis, BMC Genomics 2015, 16:94  http://www.biomedcentral.com/1471-2164/16/94

World Health Day 2015 http://www.who.int/campaigns/world-health-day/2015/en/