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Parasitic worm genome reveals potential drug and vaccine targets

Analysis of the genome of a parasitic worm that infects livestock worldwide has revealed potential targets for treatments and vaccines.

Five enzymes essential to the survival of barber pole worm have been identified with two already being studied as potential drug targets against other pathogens.

A team of scientists, including researchers from the University of Glasgow’s College of Medical, Veterinary and Life Sciences sequenced the genome of Haemonchus contortus, which resides in the gut of sheep and other livestock globally.

The genome could provide a comprehensive understanding of how treatments against parasitic worms work and point to further new treatments and vaccines.

The barber pole worm or H. contortus is part of a family of gastrointestinal worms that are endemic on 100% of farms and are estimated to cost the UK sheep industry alone more than £80 million pounds each year.

H. contortus has become resistant to all major treatments against parasitic worms, so its genome is a good model to understand how drug resistance develops in this complex group of closely related parasites and will also reveal further potential drug and vaccine targets.

In a paper published in the online journal Genome Biology, study authors Drs James Cotton and Roz Laing, from the Wellcome Trust Sanger Institute and University of Glasgow respectively, said:  “Our reference genome allows researchers to understand how H. contortus and other worms of this type acquire resistance to a wide range of anthelmintics – the drugs used to treat worm infections.

“Seeing a common theme of drug resistance in this well-characterised worm is extremely important because both people and animals are reliant on so few treatments against parasitic worms.”

The team sequenced the genome of a strain of H contortus that was susceptible to all major classes of drugs against parasitic worms. By comparing this sequence with that of worms that have acquired drug resistance, the researchers expect to reveal a wealth of information about how and why resistance has occurred.

To generate a rich source of potential vaccine and drug target candidates, the team identified sets of genes that are more active in certain stages of the parasite life cycle and within the parasite’s gut. H. contortus is a blood-feeding worm and the team identified many new gut enzymes associated with blood digestion. One of these has already shown promise as a vaccine against hookworm infections. They also identified five metabolic chokepoints – enzymes that are essential for a parasite’s survival. Two of these enzymes are already being studied as potential drug targets; one against Mycobacterium tuberculosis and another against another type of worm.

“The H. contortus genome provides essential data for further research on new control measures for this and related parasitic worms,” says Dr Collette Britton, a co-author from the University of Glasgow. “This is important to animal and human health and to increasing food production globally, which is a priority with the increase in world population and changing diets.” 

The researchers also described the full gene repertoires for known drug target families. This gives a comprehensive understanding of how several important treatments work against worms and begins to unravel why resistance has occurred in these genes.

“Not only is this worm closely related to many other parasites of livestock it is also similar to some species of worms in humans.” Professor John Gilleard, joint senior author from the University of Calgary’s Faculty of Veterinary Medicine. “This makes it an extremely important model parasite species for experimental studies. Revealing new drug targets against H. contortus could provide much-needed new treatment opportunities against parasitic worms in both animals and humans”.

The Glasgow team comprised Dr Roz Laing, Dr Collette Britton, Professor Eileen Devaney and PhD student Stephanie Johnston.


 For more information contact Stuart Forsyth in the University of Glasgow Media Relations Office on 0141 330 4831 or email stuart.forsyth@glasgow.ac.uk

Notes to Editors

Roz Laing, Taisei Kikuchi, Axel Martinelli, Isheng J. Tsai, Robin N. Beech, Elizabeth Redman, Nancy Holroyd, David J. Bartley, Helen Beasley, Collette Britton, David Curran, Eileen Devaney, Aude Gilabert, Martin Hunt, Frank Jackson, Stephanie Johnston, Ivan Kryukov, Keyu Li, Alison A. Morrison, Adam J. Reid, Neil Sargison, Gary Saunders, James D. Wasmuth, Adrian Wolstenholme, Matthew Berriman, John S. Gilleard, James A. Cotton (2013) ‘The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery’

 

Advanced online publication in Genome Biology 28th of August. DOI: 10.1186/gb-2013-14-8-r88

 

http://genomebiology.com/content/pdf/gb-2013-14-8-r88.pdf

 

Funding

 

The Haemonchus contortus genome project is funded by the Wellcome Trust.

 

Roz Laing is funded through the Scottish Government by the Strategic Partnership for Animal Science Excellence (SPASE) and Stephanie Johnston is funded through a BBSRC/KTN/Pfizer CASE PhD Studentship.

 

Participating Centres

 

  • Institute of Infection, Immunity and Inflammation, College of Medical, Sciences, University of Glasgow, Glasgow, United Kingdom
  • Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
  • Division of Parasitology, Department of Infectious Disease, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-­­1692 Japan
  • Institute of Parasitology, McGill University, Ste Anne de Bellevue, Quebec, Canada
  • Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
  • Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan,
  • Penicuik, United Kingdom
  • Department of Ecosystem and Public Health, Faculty of Veterinary Medicine,
  • University of Calgary, Calgary, Alberta, Canada
  • Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom
  • Department of Infectious Diseases and Center for Tropical and Emerging Global
  • Disease, University of Georgia, Athens, USA

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