Toxoplasma is a major health burden. In some countries more than half of the population are infected, and if they become immunosuppressed, or pick up the parasite during pregnancy the consequences can be very serious. But toxo has a close relative called Hammondia that is much more limited in how it behaves. So could studying the two agents provide us with new insights into ways to turn off toxoplasma? Chris Smith speaks to the University of Pittsburgh's Sarah Sokol…
Sarah - The lifecycle of toxoplasma is very unique. It starts in the definitive host which is the cat. In this case the parasite will undergo sexual reproduction and the sexual reproduction will produce oocysts and these oocysts would then be excreted from the cat and cat faeces. And these are very environmentally stable. So whenever another host, so an intermediate host comes in contact and ingest these oocysts they will infect that intermediate host, rapidly replicate, and then they'll eventually differentiate into these tissues cysts that results in this chronic, or latent, infection. Those can then be passed back to the definitive host to initiate sexual reproduction or it can bypass sexual reproduction and those tissue cysts can be used to infect another intermediate host. and thus the parasite can be continuously propagated just in its intermediate hosts and its asexual form.
Chris - So let's say that there is some faeces in my garden, which cats seem to love doing. Along comes mouse, encounters the cat feces replete with the toxo, mouse catches toxo, cat could eat mouse completing the lifecycle or, say a rat could come and eat the mouse and become a rat with toxo?
Sarah - Yes, yes it could.
Chris - And how does that compare with the other parasite you've been studying? What is the other parasite you've been looking at?
Sarah - So the other parasite is Hammondia Hammondi. It is very similar to toxoplasma, so it has the same definitive host, it completes sexual reproduction and the cat produced oocysts which then when are consumed by an intermediate host will establish an infection and then eventually differentiate into tissue cysts. However those tissues cysts are only infectious to a cat. So if another animal came along and at an intermediate host maybe in this case mouse they would not contract Hammondia.
Chris - So how does the parasite, the Hammondia, know it's in a cat?
Sarah - That is a great question. I wish I knew the answer to that. Ideally, we would love to be able to understand those differences because I think understanding that would help us understand why toxoplasma doesn't need to be in a cat to continue to replicate
Chris - Because Toxo is a massive global disease burden for humans isn't it? I mean estimates are that more than a billion people carry toxoplasma and it is a really serious issue for people who have immune problems or are pregnant. So if you can unpick what actually means it's able to bypass not being in a cat then actually you might have a way to intervene and turn off toxo?
Sarah - Yeah ideally that would be the optimal situation, is if we knew exactly how to manipulate toxo so that it couldn't go and infect additional intermediate hosts.
Chris - Now given that they are so closely related and so similar, can you sort of line up the two genomes and ask well where do they differ. Because perhaps those differences in behaviours are underpinned by those differences in the genetics.
Sarah - Yes. So we've done this. What's surprising is that these genomes are greater than 97 percent synthetic. So that means they have the same genes in the same place within the genome and there's really not a lot of gene loss that would account for their developmental differences.
Chris - So that makes your life a lot easier than if you've got so few differences. Are there any in there, if you look at those differences that might point towards why there is this very dramatic difference in life cycle between the two parasites?
Sarah - Not really. So most of the differences that we see are likely due to assembly differences with the genome. So it's really hard to identify what those differences are. However, what we do know is that both of these parasites differentially express different genes during their developmental life stage and so that'swhat we're trying to use in order to identify differences.
Chris - Could it be some kind of epigenetic phenomenon, whereby the environment in which they find themselves sets a bunch of epigenetic tags signalling to the organism you are not in a cat or you are in a cat and that triggers different stages.
Sarah - Yes so that's one of our most recent hypotheses and where we see this work going in the future is thinking that there has to some type of epigenetic regulation resulting in this expression difference between both parasites.