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Quantum leap in parasite worm treatment research with largest ever helminth genome study

Parasitic roundworms and flatworms (collectively known as “helminths”) cause some of the most common yet neglected tropical infectious diseases affecting more than a billion people worldwide, in addition to afflicting many important plants and animals. Such diseases include chronic and sometimes severely painful and physically disabling conditions like river blindness, schistosomiasis and hookworm infections.

Now, research led by an international team of scientists involving the largest study of helminth genomes to date is helping us to understand their biology and will accelerate our progress towards finding novel and more effective ways of fighting these parasites. “Over the last decade helminth genomes have been studied in fits and starts all over the globe and there clearly was a need to have a large-scale effort to look at these parasites collectively. So we decided to join hands with other leading researchers around the world and tackle this formidable task. Studies like this enable translational research in tropical medicine and are vital for improving global public health”, said Dr. Makedonka Mitreva who led the team from Washington University’s McDonnell Genome Institute.

In addition to the team at Washington University, the consortium comprised of leading helminth genomics researchers from the Wellcome Sanger Institute (led by Drs. Matt Berriman and Avril Coghlan) and The University of Edinburgh (led by Dr. Mark Blaxter) in England, along with many other collaborators worldwide. Together, they have discovered nearly a million new genes belonging to thousands of novel gene families many of which are likely to have important functions for parasite survival, development or to help them evade the immune system.

Scientists from Dr. Mitreva’s lab, including Drs. Rahul Tyagi and Bruce Rosa, analyzed the 1.4 million genes and determined that interestingly, these novel genes have diverse distribution among worm species, with some families showing large expansions within only a handful of related species. Many of these gene families show potential to carry out functions crucial to their biology such as feeding, tissue migration inside the host, and immunomodulation. Dr. Mitreva says, “These new genes point to various adaptations required for these worms to survive and thrive in their highly specific niches. For example, even just among the animal parasites, some live in the host’s gut and feed on its contents, while others migrate to the lungs and feed on blood.”

Because these parasites have many nutrients available directly from the host (or in some cases, symbiotic bacteria) they do not need genes to synthesize them. This is especially true for worms that spend their entire life cycles inside one or more hosts. Filarial worms are among such obligatory parasites and the study discovered many genes lost from their genomes, whose functions are presumably either not needed or are supplied by the host. For example, while comparing the metabolic potential of these worms, they discovered that filarial worms have lost the glyoxylate cycle enzymes which were known to be uniquely present in nematodes among all multicellular animals.

This study reported in the Nature Genetics today (November 5, 2018) describes a large comparative analysis involving genomes from 81 helminth species, including 45 whose genomes had never been sequenced before. “This extensive data and accompanying analysis results helped us understand how these worms survive in their peculiar niches, how they trick the host immune system to ensure their own survival, and the causes of the associated disease symptoms,” said Dr. Mitreva.

In the most directly translational part of the report, the consortium has suggested 40 high priority drug targets that may be used to discover new drugs that work against these parasites. Even though helminths have been a known scourge for mankind for most of history, there are only a few drugs that are currently used to treat them. Drug resistance is already emerging among farm animals, and the possibility that it might also arise among human parasites is a major concern. The hundreds of potential drugs suggested in this work, including many that are already approved for use in humans for other conditions, is likely to be a treasure trove for the helminth research community and will lead to accelerated introduction of new anthelmintics in near future.

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