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 parasite's intermediate hosts. Microscopic fork-tailed parasites released into the water by the snails burrow into a bather's 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 cycle again.
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 NIAID's 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 worms.
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 genomes.
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 parasite's 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 of NIH.)
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, see http://www.nigms.nih.gov.
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 http://www.nih.gov.
References: M Berriman et al. The genome of the blood fluke Schistosoma mansoni. Nature DOI: 10.1038/nature08160 (2009).
Y Zhou et al. The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature DOI: 10.1038/nature08140 (2009).
Anne A. Oplinger | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy