09:54am Monday 25 September 2017

Subtle genetic differences lead to major changes in parasites

parasites

The team looked at the evolution of these parasites and found that although their genome architecture still remains similar, the two split from their common ancestor 28 million years ago, approximately four times longer than the human-gorilla split.

Toxoplasma is arguably the most successful parasite. It can spread to any cell type in any warm blooded vertebrate species. It can cause blindness and spontaneous abortion. Alternatively, the Neospora parasite can infect far fewer hosts. It is a veterinary pathogen and causes a high number of abortions in cattle, costing the UK farming industry millions of pounds a year. The parasites, though different, are closely related.

Professor Jonathan Wastling, from the University’s Institute of Infection and Global Health, said: “We investigated these two parasites because they represent a big problem for the farming industry and, in the case of Toxoplasma, for public health also. They are, however, genetically very closely related, but show very different features, such as Toxoplasma ability to infect human.”

The team found that a gene that helps the Toxoplasma pathogen to evade the host’s immune system and enter the cell is missing from neospora. The lack of this single gene means Neospora cannot evade the immune response in mice and may not be able to evade the immune response in other species. This could explain why Neospora has a more limited host range.

Professor Wastling said: “The fact that Neospora has lost key virulence factors might be thought of a good thing because it should cause less disease. However, it appears that it might be the loss of these genes that has resulted in Neospora becoming well adapted to cattle and has developed the ability to be passed down the generations from cow to calf.”

Dr Adam Reid, from the Wellcome Trust Sanger Institute, said: “The question we wanted to answer was; what causes this difference in virulence between Toxoplasma and Neospora? We used genome sequencing to probe the parasites for differences that might underlie the way they spread and how they have diverged.”

The team also found that although the genetic differences between the two parasites are minor, there is a significant difference in the number of surface proteins found in both parasites. Neospora has more surface proteins, nearly twice as many as Toxoplasma, but fewer are active. Although this is difficult to interpret, the researchers hypothesise that a larger number of proteins are needed to restrict the parasite’s host range.

The next step for the team is to examine the genomes of other parasites within the same family as Toxoplasma and Neospora to better characterise the function of the genes and surface proteins. By deciphering which of these surface proteins are involved in the cell invasion process, it may be possible to develop vaccines for both of these parasites

The research, funded by the BBSRC, is published in PLoS Pathogens.

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