Genome of schistosome parasite published
16 July 2009
An international team, including researchers from the Wellcome Trust Sanger Institute, has today published the complete genome sequence of ‘Schistosoma mansoni’, a parasitic worm (commonly known as a blood fluke) that causes schistosomiasis. This disease is a major global problem, causing 280 000 deaths in sub-Saharan Africa alone each year, according to the World Health Organization.
During the study, which was part-funded by the Trust, the researchers identified several potential new drug targets. This is of major importance as there is currently only one drug used to treat the disease, and there are growing fears that the parasites will become resistant to it.
“This genome sequence catapults schistosomiasis research into a new era,” says Dr Matthew Berriman of the Wellcome Trust Sanger Institute and first author and co-leader of the study. “It provides a foundation for understanding aspects of the parasite’s complex biology as well as a vehicle to immediately identify new targets for drug treatment.”
To identify such targets, researchers usually exploit differences between the pathogen and its human host. However, ‘S. mansoni’ is far closer to us in evolutionary terms than many of the major parasites whose genomes have been sequenced. So, the team used a novel approach of looking for similarities between humans and the parasite to try and identify existing drugs that could be used to treat the disease.
First, the team searched a database of current human drugs and found matches to 26 genes in the parasite, a few of which are being explored, but many of which are novel. Secondly, the team matched parasite genes to known drug targets and found more than 90 candidates that meet minimal requirements of short treatment course and ready availability.
The researchers used a whole-genome shotgun method to sequence the ‘S. mansoni’ genome. It contained almost 12 000 genes - about half as many as the human genome.
‘S. mansoni’ is one of three species of the ‘Schistosoma’ parasite that, because of a deficit in lipid levels, are dependent on a human host to complete their life cycle. The parasites develop in the blood system of the human and can also pass to the liver, lungs and bladder. When mature, they lay eggs in the intestinal wall. While some of the eggs are passed as faeces, surviving eggs can travel to the liver, where they induce an extreme inflammatory immune response, which is the cause of the schistosomiasis.
The publication of this genome comes alongside that of the ‘S. japonicum’ species, also a common cause of schistosomiasis. Together, the sequences provide new avenues for study in evolution, genetics and functional genomics.
Image: A pair of mating ‘Schistosoma mansoni’ flukes; CDC/Dr. Shirley Maddison
Reference
Berriman M et al. The genome of the blood fluke Schistosoma mansoni. Nature 2009; doi: 10.1038/nature08160