Parasitic worm genome and biology provides a solid basis for the development of new interventions
Researchers have deduced essential biological and genetic information from the genome sequence of the whipworm, an intestinal parasitic worm that infects hundreds of millions of people in developing countries.
This information acts as the foundation for the development of new strategies and treatments against this debilitating parasite.
The whipworm is one of three types of soil-transmitted parasitic worms that collectively infect nearly two billion people. While infections often result in mild disease they may also lead to serious and long-term damage such as malnutrition, stunted growth and impaired learning ability. The full extent of worm-associated morbidity and the effect it has on socio-economic development in endemic countries is unknown.
This unusual parasite bores miniature tunnels through the lining of the large intestine where it may live for years. The study has identified molecules that the parasite uses for tunnelling, how the parasite limits the damage it inflicts, and how the immune system responds to infection.
"Worm infections are an enormous public health problem across the Developing World and with so few effective drugs, the emergence of drug resistance is an ever present risk," says Dr Matthew Berriman, senior author from the Wellcome Trust Sanger Institute. "Our work starts to unravel the whipworm's intimate relationship with humans and paves the way for new approaches to prevent or clear whipworm infections.
"Making these genome sequences freely available will provide an enormous boost to the entire research community that is working on interventions to prevent or treat worm-associated disease."
The team sequenced the genome of both a human- and a mouse-infective form of the whipworm and examined the genes that are most active and may be essential for its survival. Equipped with this information, the team mined for drug targets that could be used against the whipworm and potentially other parasitic worms.
The genome sequence and the range of proteins the whipworm produces provides a biological understanding of the extraordinary niche this worm has evolved to live in. The team found specific digestive enzymes secreted by the whipworm may burrow through the cells in the gut wall. Other enzymes secreted by the parasite seem to contain the 'collateral damage' caused by these digestive enzymes to reduce inflammation and damage to the host's cells.
"In my experience working with children in Ecuador, these parasites, particularly when present in large numbers in an individual, can have profound effects on health," says Professor Philip Cooper, author and clinician from the Liverpool School of Tropical Medicine. "With more than 800 million children worldwide in need of treatment against these particular worms, and because we have only one or two drugs that are safe and effective against these parasites, it is essential that we focus our research on finding new treatments before resistance to the drugs we have has a chance to develop. This study not only opens doors for the development of new drugs but also may allow us to identify already existing drugs used for other diseases that might be effective against this parasite and other types of worms.
"Getting to grips with the genomes and the underlying biology of parasitic worms such as the whipworm is our best option to tackle this growing global problem."
Whipworm eggs are currently being tested in clinical trials as a treatment against various autoimmune diseases, as it is thought that worm infections may reduce the inflammation associated with disorders such as multiple sclerosis and inflammatory bowel disease. To determine how the immune system responds to infection, mice were exposed to the mouse-specific type of whipworm. The researchers found that infection caused changes to the activity of many mouse genes that have been associated with inflammatory diseases such as ulcerative colitis.
"Although whipworms can be detrimental to human health and economic growth in some regions, they are also important in defining our immune system's 'set point' and ensuring we make the right level of immune response during disease," says Professor Richard Grencis, senior author from The University of Manchester. "The present study shows how both the parasite and the host respond to each other at a level of detail never seen before, that will help us identify how to exploit the ways in which the worm modifies our bodies.
"This finely tuned interaction that has developed over the course of evolution can lead us to design better drug treatments and more effective clinical trials using worms and their products."
Notes to Editors
Publication Details Foth BJ, Tsai IJ, Reid AJ, Bancroft AJ, et al (2014). The whipworm genome and dual-species transcriptomics of an intimate host-pathogen interaction. Nature Genetics. DOI: 10.1038/ng.3010
Participating Centres Please see the paper for a full list of participating centres.
The Liverpool School of Tropical Medicine (LSTM) has been engaged in the fight against infectious, debilitating and disabling diseases since 1898 and continues that tradition today with a research portfolio in excess of well over £200 million and a teaching programme attracting students from over 65 countries. http://www.lstmliverpool.ac.uk/
The University of Manchester, a member of the prestigious Russell Group of British universities, is the largest and most popular university in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. According to the results of the 2008 Research Assessment Exercise, The University of Manchester is one of the country's major research institutions, rated third in the UK in terms of 'research power', and has had no fewer than 25 Nobel laureates either work or study there. The University had an annual income of £807 million in 2011/12. http://www.manchester.ac.uk/
The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. http://www.wellcome.ac.uk
Mary Clarke | Eurek Alert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences