Genome of man’s rare brain worm detailed in online ‘WormBase’ (Wired UK)


Nagui Antoun


Researchers have succeeded
in sequencing the genome of a rare tapeworm
that resided in the
brain of a British man for four years.

There have only been 300 reports of the worm, known as Spirometra
erinaceieuropaei, since 1953 and it has never appeared in the UK
before. As the parasite is so rare it is not known exactly how it
entered the man’s body, although it is possible that it could have
been caused by the man consuming tiny crustaceans from lakes,
eating raw meat from amphibians and reptiles or by using a raw frog
poultice, which is a Chinese remedy to cause sore eyes.

Although the man is now systemically well now, the worm causes
sparganosis in humans, which is an inflammation of bodily tissues.
When the parasite is inside the brain this can cause seizures,
memory loss and headaches.

In this case, the worm in the man’s brain was found to be only
1cm long, but before it was diagnosed and removed, it had travelled
5cm from the right side of the brain to the left. It took four
years of eliminating other diseases, followed by regular MRI scans
to discover what was causing the man’s headaches and seizures.
Comparing the MRI scans, it is possible to see the worm travelling
slowly across the brain.


Nagui Antoun


Identification

Even when the parasite was spotted, it wasn’t possible to
identify it as Spirometra erinaceieuropaei. “The key thing in this
case was that the pathologist recognised it was a parasite,” Matt
Berriman tells WIRED.co.uk. It was removed using precision surgery
and placed on a histology slide. “They pulled it out essentially
with a biopsy needle.”

Researchers then had to go about identifying the worm. This took
several months — and not just because we’re not used to seeing
such parasites in the UK. Even in countries like China and Korea
where the parasite originates, it is so rare that there is very
little information known about it.

“The clinical histology slide offered us a great opportunity to
generate the first genome sequence of this elusive class of
tapeworms,” says Hayley Bennett from the Wellcome Trust Sanger
Institute. Bennett, who was first author of the study detailing the
genetic findings from the parasite, points out that because they
only had a very tiny piece of DNA to work with — “just 40
billionths of a gram” — they had to make some very tough calls
about exactly they wanted to find out from the DNA.

In all creatures there is one particular gene known as “the
barcode of life” that can be sequenced in order to determine the
exact species of the animal. When they did this to the parasite,
the researchers discovered that it was a Spirometra
erinaceieuropaei worm, and that of the two known
sparganosis-causing worm species, the one in the man’s brain was
the more benign of the pair.

They also managed to generate sufficient DNA sequence data to put
together a draft genome, which is now being used to investigate
known and potential treatment targets.

“We made a couple of sequencing libraries — one was very good,”
says Berriman. This was enough to piece together the draft genome
quite nicely. He admits though that “this is not a good example
about how to build a genome”. Ideally to make a reference genome
you wouldn’t need to use a histology slide at all, he says.

Despite the worm being so small, its genome is still a third
the size of a human genome and therefore cost probably several
thousand pounds to sequence, Berriman speculates. As sequencing
techniques improve, the process should get cheaper and the results
should be of a better quality, he says. “Hopefully there will be
longer stretches of sequence you get by default.”

If only there was more genetic information available about
parasites, the process of identifying them could be reduced to a
single day. “We were quick but it still took months,” says
Berriman. “In future, I’d like to think the time from getting
biological material to making a molecular diagnosis could be
reduced.”

WormBase ParaSite 

He is already working on a solution to this. A new open-access
database called WormBase
ParaSite
has been founded by the Wellcome Trust Sanger
Institute in conjunction with the European Bioinformatics
Institute, with the aim of collecting masses of genomic data about
parasitic worms. The idea is that by collating research into the
genomes of different species of worms, clinicians around the world
will have a robust resource to help them more easily identify and
treat the massive disease burden parasites
cause, which exceeds that of malaria or tuberculosis.


Screenshot


The database is already online and currently contains draft
genome sequences for over 80 species of parasite, including the
information gleaned from the Spirometra erinaceieuropaei found in
the British man’s brain. The more genetic code that is collected
there, the more likely it is that researchers will be able to
identify genetic similarities between species on the kind of scale
that will impact how diseases caused by parasites are treated.

Some of the parasites out there are so rare that existing
research into them is little-known and obscure. “To set the project
up we literally started with Google,” says Berriman. What they
found was that almost every species has two or three investigators.
Through the WormBase project, Berriman and his colleagues are
“trying to collaborate with everyone”.

Already by the studying the sequenced genome of the British
man’s brain-invading worm, it is possible to predict the likely
activity of known drugs on this elusive group of tapeworms. “The
genome sequence suggests that the parasite is naturally resistant
to albendazole — an existing anti-tapeworm drug. However, many new
drug targets that are being explored for other tapeworms are
present in this parasite and could offer future clinical
possibilities,” Berriman says. “As the number of similar cases
grows, we should also be able to say with greater confidence where
individual parasites come from and piece together a more detailed
picture of how each patient is infected.”

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21 November 2014 | 5:34 pm – Source: wired.co.uk

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