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Haemonchus contortus (Barber Pole) worms in situ in
a sheep gut.
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Aug.
28, 2013 — Researchers have identified five enzymes that are essential to the
survival of a parasitic worm that infects livestock worldwide and is a great
threat to global food security. Two of these proteins are already being studied
as potential drug targets against other pathogens. The team sequenced the
genome of Haemonchus contortus, or the barber pole worm, a well-studied
parasitic worm that resides in the gut of sheep and other livestock globally.
This 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.
“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,” says Dr James Cotton, senior author from
the Wellcome Trust Sanger Institute. “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.
“The
H. contortus genome provides a rich and essential platform for future research
in this and other types of parasitic worms,” says Professor Neil Sargison,
author from the University of Edinburgh, Royal (Dick) School of Veterinary
Studies. “With the world population set to exceed nine billion by the year
2050, improving the security of our food supply is crucial. Getting to grips
with genomes such as that of H. contortus, is our best option to tackle the
issue of drug resistance and develop new drugs against parasitic worms to
address this issue.”
To
generate a rich source of potential vaccine and drug target candidates, the
team identified a set of genes that are more active in certain stages of the
parasite life cycle and within the parasite’s gut. They also identified five
metabolic chokepoints – enzymes that are essential for a parasite’s survival.
Two of these enzymes are already being studies as potential drug targets; one
against Mycobacterium tuberculosis and another against another type of worm.
To
discover these targets, the team determined when and where each gene is turned
on or off in the cells and tissues of H. contortus to reveal new insights into
the worm’s lifecycle. The result is the most extensive dataset of its kind for
any gastrointestinal worm and is expected to provide a valuable resource for
future investigations.
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 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.
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