Study helps understand how parasitic worms cause disease and uncovers potential new deworming drugs

The largest genomic study of parasitic worms to date has identified hundreds of thousands of new genes and predicted many new potential drug and drug targets. Research from the Wellcome Sanger Institute, Washington University in St. Louis, Edinburgh University and their collaborators will help scientists understand how these parasites invade us, evade the immune system and cause disease.

Posted in Natural genetics Today (November 5), the study could lead to new deworming treatments to help prevent and treat diseases caused by parasitic worms around the world.

Parasitic worms cause some of the most neglected tropical diseases, including river blindness, schistosomiasis and hookworm, and kill more than a billion people worldwide. Infections can last for many years or even decades, resulting in severe pain, massive physical disabilities, developmental delay in children, and social stigma associated with the deformity. Despite the huge health burden inflicted on many of the world’s poorest countries, little investment has gone into research on parasitic worms.

To understand how worms can infest and live inside people, the researchers compared the genomes of 81 species of roundworms and flatworms, including 45 that had never been sequenced before. Their analysis revealed almost a million new genes that had never been seen before, belonging to thousands of new gene families, and which showed huge variations in their distribution between species.

Researchers have found that some species of worms have huge families of genes to help them colonize the host’s gut, migrate through host tissues, or digest food. Other species had many gene families that affect the host’s immune system to keep the worm hidden.

Dr Matt Berriman, lead author from the Wellcome Sanger Institute, said: “Little is known about the biology of many species of parasitic worms, so we used a broad comparison of their genomes to uncover the most striking genetic differences between them. We have discovered many new genes and gene families to help understand how worms live and migrate inside us and other animals. This dataset will propel worm research into a new era of discovery.

Anti-worm treatments have remained unchanged for years and are often insufficient. Also, overreliance on just a few existing drugs can lead to drug resistance. To search for new interventions, the researchers mined the dataset of 800,000 worm gene sequences to predict new targets for worm drugs and anti-worm drugs. Using the ChEMBL* Database of Existing Drugs and Chemicals, they narrowed the list down to 40 high-priority drug targets in worms and hundreds of possible existing drugs or compounds.

Dr Avril Coghlan, chief analyst at the Wellcome Sanger Institute, said: “The spectrum of drugs available to treat worm infections is still very limited. We focused our research on examining existing drugs for human diseases. This can provide a fast track. to identify existing drugs that could be repurposed for deworming.”

Further research could lead to a host of new treatment possibilities to help improve the lives of millions of people suffering from neglected tropical diseases caused by these worms.

In addition to discovering new genes and potential new possibilities for deworming, the 81 genome sequences allow researchers to place each worm on the evolutionary tree of life, to help understand how parasites evolve.

Professor Mark Blaxter, author from the University of Edinburgh, said: “All parasites have evolved from free-living ancestors, and comparing their genomes has shown the changes that occur when a species becomes a Parasites affect much of the natural world, and these genomes hold a record of how these fascinating animals – and their amazing biology – came to be.”

Parasite genomes also provide clues as to how worms avoid being attacked by our immune system. This could help us understand the immune system itself and ultimately allow us to harness the natural power of the immune system to improve human health.

Associate Professor Makedonka Mitreva, lead author from the McDonnell Genome Institute at the University of Washington, said: “Parasitic worms are among our oldest enemies and have evolved over millions of years to become expert manipulators of the system. human immune system. This study will lead to a better understanding of the biology of these important organisms, but may also help us better understand how our immune system can be harnessed or controlled.”

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