|Genomes of Parasitic Flatworms Decoded
Information Could Lead to New Treatments for Schistosomiasis
Two international research teams have determined the complete
genetic sequences of two species of parasitic flatworms that cause
schistosomiasis, a debilitating condition also known as snail fever.
Schistosoma mansoni and Schistosoma japonicum are the first sequenced
genomes of any organism in the large group called Lophotrochozoa,
which includes other free-living and parasitic flatworms as well
as segmented roundworms, such as the earthworm.
The research was supported in part by the National Institute
of Allergy and Infectious Diseases (NIAID), one of the National
Institutes of Health (NIH), and is published in the current issue
of Nature. The genomic information obtained through these sequencing
projects suggests ways to design drugs or other compounds targeted
specifically at proteins or other gene products required by the
parasite to find or survive in its human or snail host.
"Chronic infection with Schistosoma parasites makes life
miserable for millions of people in tropical countries around the
globe, and can lead to death," says NIAID Director Anthony
S. Fauci, M.D. Anemia, fever, fatigue and other symptoms can make
it difficult for sufferers to work or go to school, he adds. "New
drugs and other interventions are badly needed to reduce the impact
of a disease that lowers quality of life and slows economic development."
People become infected with Schistosoma when they wade or bathe
in water inhabited by tiny snails that are the parasiteís intermediate
hosts. Microscopic fork-tailed parasites released into the water
by the snails burrow into a batherís skin and travel to blood vessels
that supply urinary and intestinal organs, including the liver,
where they mature. Female worms, which live inside the thicker
males, release many thousands of eggs each day. Eggs shed in urine
and feces may make their way into snail-inhabited water, where
they hatch to release parasites that seek out snails to begin the
Schistosomiasis cases top 200 million every year, and some 20
million people are seriously disabled by severe anemia, chronic
diarrhea, internal bleeding and organ damage caused by the worms
and their eggs, or the immune system reactions they provoke. Though
best known for causing chronic illness, schistosomiasis also kills;
in sub-Saharan Africa alone it kills some 280,000 people each year.
Since the 1980s, the inexpensive anti-worm medication praziquantel
has been administered to people in nationwide schistosomiasis control
programs in dozens of tropical countries where the disease is common.
While the drug is effective, it does not prevent a person from
becoming re-infected through exposure to infested waters.
"The mass administration of a single drug increases the chance
the parasites will become resistant to it," notes Martin John
Rogers, Ph.D., a program officer in NIAIDís Parasitology and International
Programs branch. "Reliance on one drug is not a satisfactory
long-term solution to the problem of schistosomiasis."
Finding new drug targets was a key goal of the team that sequenced
the S. masoni genome. Led by NIAID grantee Najib M. El-Sayed, Ph.D.,
of University of Maryland, College Park, the group determined the
sequence of 363 million nucleotides, encoding 11,809 genes. Analysis
of the genes and the proteins they encode revealed the loss of
some types of genes (and proteins) and expansion of other gene
families relative to corresponding genes found in non-parasitic
These genetic gains and losses are tied to the parasitic lifestyle
of Schistosoma. For example, the researchers detected a large percentage
of genes encoding proteases (enzymes that break down proteins.)
Parasites, like Schistosoma, that must bore through skin and other
tissues to invade their hosts require many such enzymes. Befitting
a parasite that must navigate murky waters to find its intermediate
host and later must travel through several tissue types in its
human host, Schistosoma flatworms have sophisticated neurosensory
systems that allow them to, for example, detect chemical, light
and temperature levels in water or inside their hosts. Genes that
encode signaling proteins involved in these neurosensory processes
made up a significant proportion of both S. masoni and S. japonicum
The team responsible for the S. masoni genome also used bioinformatic
computational techniques to translate genetic sequence information
into maps of over 600 enzymatic reactions arrayed in multiple metabolic
pathways. The analysis revealed 120 flatworm enzymes that could
potentially be targeted with drugs that would disable the enzyme
and inhibit the parasiteís metabolism.
Finally, in an effort to find currently marketed drugs (such as
protein or enzyme inhibitors) that might also be deployed against
schistosomiasis, the researchers compared information about parasite
proteins to a database of drugs directed at other human diseases.
They found 66 instances of currently marketed drugs that might
also be effective against schistosomiasis. "This list represents
a good starting point, but, of course, more research is needed
to determine whether any of the compounds could also be used to
treat schistosomiasis," says Dr. Rogers.
NIAID provided major funding for the S. masoni genome sequencing.
Additional support was provided by the Wellcome Trust of Great
Britain and through grants from the Fogarty International Center
and the National Institute of General Medical Sciences (both components
The S. japonicum genome was produced by an international team
of researchers led by Zhu Chen, Ph.D., Ze-Guang Han, Ph.D., and
Shengyue Wang, Ph.D., of the Chinese National Human Genome Center,
Shanghai. NIAID grantee Zheng Feng, M.D., of the Chinese Center
for Disease Control and Prevention, is a coauthor on the paper.
For more information on NIAID research on schistosomiasis and
other neglected tropical diseases, see http://www3.niaid.nih.gov/topics/tropicalDiseases/default.htm.
For a diagram of Schistosoma lifecycle, see http://www3.niaid.nih.gov/news/newsreleases/2009/SchistomesLifecycle.htm.
NIAID conducts and supports research — at NIH, throughout the United
States, and worldwide — to study the causes of infectious
and immune-mediated diseases, and to develop better means of preventing,
diagnosing and treating these illnesses. News releases, fact sheets
and other NIAID-related materials are available on the NIAID Web
site at http://www.niaid.nih.gov.
NIGMS is a part of NIH that supports basic research to increase
our understanding of life processes and lay the foundation for
advances in disease diagnosis, treatment, and prevention. For more
information on the Institute's research and training programs,
The Fogarty International Center, the international component
of the NIH, addresses global health challenges through innovative
and collaborative research and training programs and supports and
advances the NIH mission through international partnerships. For
more information, visit www.fic.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases.
For more information about NIH and its programs, visit www.nih.gov.
M Berriman et al. The genome of the blood fluke Schistosoma mansoni. Nature DOI:
Y Zhou et al. The Schistosoma japonicum genome reveals features
of host-parasite interplay. Nature DOI: 10.1038/nature08140