How do parasites worm their way in?

The Strongyloides parasitic worm Credit: Mark Biney, University of Bristol

More than a billion people around the world are infected with parasitic worms. In the UK, parasites and worms don’t affect our daily lives very much. Although most children get Enterobius, or thread worm (pinworm in US) at some point, while itchy, it doesn’t cause serious harm. It’s a different story in other parts of the world, where soil-transmitted nematodes can slow children’s growth.

Unfortunately we still understand little about how parasites are able to get inside you and survive there. I have been involved in a collaboration with research groups from the UK, Japan, Taiwan, Germany, Mexico, USA and Australia to study how some worms have evolved to make their homes inside us. We sequenced the genomes of a group of worms and discovered two groups of genes associated with parasitism.

Soil-transmitted nematodes are rarely deadly, but they cause much suffering and maintain the cycle of poverty in parts of Africa, South America and South East Asia. Strongyloides is one group of these parasites. A particularly terrible form of infection can occur in immunocompromised individuals. Here, immunosuppressive drug treatment can cause hyperinfection syndrome in which an individual is overcome with worms. If untreated this can lead to death.

This worm is not only an important cause of disease, it is an excellent model system to understand the evolution of parasitism. Several species of Strongyloides have evolved from a free-living, non-parasitic ancestor. If we can understand what is different about these parasitic species compared to free-living relatives, we can identify adaptations that help the parasite invade our bodies and survive there.

Evolution and comparative genomics of Strongyloides and relatives

Thanks to our collaborators we were able to collect DNA from six different species of Strongyloides worm. We sequenced their genomes and then compared the free-living species to the parasitic ones to determine which genes are important for being a parasite. We identified two particular groups of genes: proteases (astacins) and cysteine-rich proteins (SCP/TAPS).

To test the importance of these genes in parasitism we used an unusual feature of the Strongyloides life cycle. While these parasites spend most of their time living inside another animal, they also have a free-living stage in the soil. We were able to use RNA sequencing to look at which genes are used in the parasitic stage and compare this to those used in the free-living stage.

The parasitic female, free-living female and infective third-stage larvae transcriptomes of Strongyloides spp.  Taken from Hunt V et al. (2016) Nature Genetics DOI: 10.1038/ng.3495

We expected that the genes important for parasitism should only be switched on in the parasitic stages of the life-cycle. Our analysis identified the same two groups of genes: proteases and cysteine-rich proteins. We then went on to show that these genes produce proteins released by the worm, suggesting that they interact directly with the host. This provides more evidence of their importance for parasitism.

So where does this work lead us? We are confident that these genes are involved in parasitism. The next goal is to understand how the genes work. They may help the parasite to digest our tissues, or inhibit our immune system. Understanding their role may help to develop new interventions such as drugs and vaccines.

Interestingly these genes are common in other parasitic worms and so this work could help our understanding of a range of diseases caused by soil-transmitted nematodes.