Combatting toxoplasmosis

At first glance, a parasite caught from a cat litter tray doesn’t sound like it should have much in common with malaria. But malaria is a close relative of Toxoplasma gondii; and the discovery by Glasgow’s Marcus Meissner, that, when toxoplasma grows inside our cells, it assembles a communications network that synchronises the growth of the parasites, could reveal a new way to combat both bugs. Chris Smith heard how...

Marcus - Toxoplasma is a single-celled organism. It’s a parasite that can only live inside other cells. It is commonly infecting cats, but it also is carried by other warm-blooded animals including us, humans. Amazingly, up to one-third of the UK population is actually chronically infected with this parasite. Meaning, once infected, you will carry this parasite within yourself for the rest of your life mainly as tissue cysts in your brain but also in your muscle tissue.

Chris - How do most people pick it up?

Marcus - There are two major routes for the information. One is directly from the cat, eggs are shared with the faeces of the cats up to 2 million a day. The other route is via eating undercooked meat.

Chris - Once a person picks it up, what happens then?

Marcus - Then the parasites starts with an acute infection which is usually harmless for most people. It’s like a common cold or flu-like symptoms. However, then the parasite differentiates into persistent forms and these form tissue cysts in the brain and in the muscle. And so, the medical importance is for immune-compromised people where the immune system breaks down, there, the tissue cysts reactivate and it can cause encephalitis and brain damage. The other problem is, if a pregnant person gets infected for the first time. the parasite can cross the placenta and infect the embryo and that can cause heavy organ damage.

Chris - What have you been trying to find out about it?

Marcus - It’s obviously already important to study it for its own right as a human pathogen, but it’s also a very good model system for other parasites of the same family, the apicomplexans which includes malaria. What we wanted to find out is how the parasite actually invades the host cell because in order to survive, the parasite has to invade a host cell – in case of malaria, that’s our red blood cells – and also how the parasite replicates inside the host cell. So we focused our attention on a protein called actin which is scaffolding protein found in many different cells. However, in these parasites, no one knew if this protein can actually form a scaffold. We found a new way of imaging this protein inside the cells and found a really amazing network that is formed between individual parasites in the cell which the parasites use to communicate with each other to exchange material and to make sure that they have a synchronised cell cycle. Meaning, that all parasites replicate at the same time.

Chris - So, we got this situation where this parasite gets into a cell, whether it’s malaria or in this case, toxo, and once it’s in the cell and it starts to grow or replicate, it’s orchestrating this scaffolding which is connecting the replicating or growing progeny together, both chemically and physically. That seems to play a big role in how they grow and develop.

Marcus - Yes, that is correct. so we find for example that if we disrupt this scaffold, the parasites are sort of crippled. Meaning, they cannot really finish their replication cycle and you end up these parasites that cannot leave the host cell anymore. So they are trapped inside the host and that is of course a way to interfere with the further transmission of the parasite.

Chris - Just before we come on to what the implications of that might be, what was the imaging technique that you use to enable you to see what these parasites were doing inside cells like these?

Marcus - The trick was really that an antibody can be expressed in the parasite that binds to the scaffolding protein, only then it makes a scaffold. This antibody gives a fluorescence signal and then using super-resolution microscopy, they could make a 3D model of the scaffold and using time laps imaging, meaning, we made movies of the behaviour of the parasite, we were able to identify material that is transmitted or transferred in between the parasites.

Chris - Do you think it’s something as simple that if all of the parasites replicate or grow in a cell at the same time, then they're going to be able to share the resources that they're making at the same time, and that’s a very efficient way because you’ve got a big job lot of what you need, all in one place at one time, you share it all out, and you can grow much more effectively?

Marcus - That is actually one of our hypothesis. At the moment, we were able to detect and describe the network but we are not really 100 per cent sure yet what is the exact function of the networks. So, we don’t know the mechanisms yet.