June 27, 2009

Scientists Decode Genomes of Deadly Parasitic Flatworms

Image of long, glowing flatworms Schistosoma mansoni, one of the flatworms that cause schistosomiasis.Dr. Sulzer, CDC

Scientists have sequenced the complete genomes of 2 flatworms that cause schistosomiasis, a devastating tropical disease. The accomplishment provides an invaluable resource for developing new tools to treat the disease.

Schistosomiasis—also known as snail fever—is a neglected tropical disease prevalent in Africa, South America and Asia. Each year, more than 200 million people are infected worldwide. Ten percent of infected people develop a weakened immune system, severe anemia, chronic diarrhea, and organ damage caused by the worms and their eggs. The disease mainly affects people living in areas where water is unsafe, sanitation is inadequate, and basic health care is unavailable.

Microscopic Schistosoma parasites infect people who are wading, swimming or bathing in fresh water inhabited by tiny snails, which serve as intermediate hosts. The parasites in the water burrow into human skin and travel in the blood vessels that supply urinary and intestinal organs. After the worms mature and reproduce, the eggs can be released back into the water through urine or feces, starting the cycle again.

The main treatment for schistosomiasis is a drug called praziquantel. While effective, the drug doesn't prevent re-infection, and there's a danger the parasites will become resistant to it.

Two international research teams have now sequenced the genomes of S. mansoni and S. japonicum, 2 of the 3 major species of flatworm that cause schistosomiasis. Their papers were published together on July 15, 2009, in the journal Nature. NIH's National Institute of Allergy and Infectious Diseases (NIAID) partly funded both teams' work.

S. mansoni and S. japonicum contain 11,809 and 13,469 protein coding genes, respectively. By comparing these genomes to those of non-parasitic worms, the researchers were able to map out metabolic networks that are essential to the worms' parasitic lifestyle and thus potential areas of vulnerability. For example, a large percentage of genes encode proteases, enzymes that break down proteins. Parasites like Schistosoma must bore through skin and other tissues to invade their hosts, requiring many such enzymes.

Schistosoma must also have sophisticated systems to allow them to travel from their snail host through murky waters and several tissue types of their human hosts. A significant proportion of their genomes are thus dedicated to neurosensory systems that allow them to detect chemical, temperature and light levels in both the water and their hosts.

The team responsible for the S. mansoni genome used bioinformatics screens to identify drug targets. The researchers compared information about parasite proteins to a database of currently marketed drugs directed at other human diseases. The screen exposed 66 drugs that could potentially inhibit the parasite's metabolism.

“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 Dr. Anthony S. Fauci. Decoding the genomes of these parasites is the first step in developing drugs and vaccines that are urgently needed to combat schistosomiasis.

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