The largest genomic study of parasitic worms so far has identified hundreds of thousands of new genes and predicted many new potential targets for drugs and drugs. Research from the Wellcome Sanger Institute at the University of Washington in St. Louis at the University of Edinburgh and its collaborators will help scientists understand how these parasites invade us, flee the immune system and cause disease.
Reported in Genetics of Nature today the study may lead to new treatments for deworming to help prevent and treat diseases caused by parasitic worms around the world.
Parasitic worms cause some of the most neglected tropical diseases, including onchocerciasis, schistosomiasis, and hookworm, and are damaging the lives of more than a billion people worldwide. Infections can last for many years or even decades, leading to severe pain, massive physical deficiencies, delayed child development, and social stigma associated with deformity. Despite the enormous health burden inflicted on many of the world's poorest countries, there has been little investment in the research of parasitic worms.
To understand how worms can infest and live within people, the researchers compared the genomes of 81 species of round worms and worms, including 45 that had never been sequenced. Their analysis revealed nearly a million new genes that had not been seen before, belonging to thousands of new gene families, and which had huge variations in the way they were distributed among species.
The researchers found that some species of worms had huge families of genes to help them colonize the host's gut, migrate through host tissue or digest food. Other species had many families of genes that affect the host's immune system to keep the worm hidden.
Dr. Matt Berriman, senior author of the Wellcome Sanger Institute, said: "Little is known about the biology of many species of parasitic worms, so we use a broad comparison of their genomes to discover the most striking genetic differences between them. genes and gene families to help understand how worms live and migrate within ourselves and other animals. "This set of data will catapult the worm research into a new era of discovery."
Anti-worm treatments have remained unchanged for years and are often inadequate. In addition, excessive reliance on just a few existing medications can lead to drug resistance. To search for new interventions, the researchers extracted the data set of 800,000 gene sequences from worms to predict new targets for drugs and antiworm drugs. Making use of the ChEMBL * database of existing drugs and chemicals, they narrowed the list to 40 high-priority drug targets in worms and hundreds of possible existing drugs or compounds.
Dr. Avril Coghlan, lead analyst at the Wellcome Sanger Institute, said: "The spectrum of drugs available for the treatment of worm infections is still very limited, and we have focused our research on existing drugs for human diseases. route to identify existing medicines that could be reused for deworming. "
Further research may lead to a host of new treatment possibilities to help improve the lives of millions of people suffering from the neglected tropical diseases caused by these worms.
In addition to discovering new genes and potential new de-worming possibilities, the 81 genome sequences allow researchers to place each worm on the evolutionary tree of life to help understand how parasites evolve.
Mark Blaxter, an author of the University of Edinburgh, said: "All parasites evolved from free-living ancestors, and comparing their genomes showed the changes that happen when a species becomes a parasite." Parasites Affect Most of the Natural World , and these genomes have a record of how these fascinating animals – and their surprising biology – came into being. "
The genomes of the parasite also provide clues about how worms avoid being attacked by our immune system. This could help our understanding of the immune system itself and ultimately allow us to use the natural power of the immune system to improve human health.
Makedonka Mitreva, a senior author at the University of Washington's McDonnell Institute of Genome, said: "Parasitic worms are some of our oldest enemies and have evolved over millions of years to be specialized manipulators of the human immune system. better understanding of the biology of these important organisms, but it can also help us better understand how our immune system can be harnessed or controlled. "
Genome of parasitic worms reveals potential drug targets
Comparative genomics of the major parasites, Genetics of Nature (2018) DOI: 10.1038 / s41588-018-0262-1
* ChEMBL is a database of bioactive molecules with drug-like properties at the EMBL European Bioinformatics Institute.