Scientists find potential schistosoma drug target

A schistosome parasite magnified 256 times Copyright: National Cancer Institute: Bruce Wetzel & Harry Schaefer

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[BEIJING] Chinese scientists have identified a group of proteins that may help the schistosomiasis parasite survive host attacks.

The study was published in the July issue of the Chinese Science Bulletin, and the researchers hope their results will provide clues to identify drugs targeting the key schistosome proteins.

In previous efforts, scientists mapped the structure of all schistosomiasis proteins (see Protein map raises hopes for schistosomiasis drugs). 

Yu Fudong, a doctoral student from Shanghai Institutes for Biological Sciences, of the Chinese Academy of Sciences, and colleagues have discovered the role of a group of proteins on the parasite’s surface called the ‘EF-hand’.

“Previously, we only knew the group of proteins could induce immune reactions in hosts, but how they perform this function was unknown,” Yu told SciDev.Net.

Using a method called bioinformatics, the scientists compared the detailed structural information of the EF-hand proteins and related host proteins with a database of thousands of other proteins whose functions are already known.

According to Yu, similarities in protein structure and similar locations in cells suggest similar functions.

The researchers used computers to look at how the EF-hand proteins interact with the host, and found that the group has played an important role in the parasite’s evasion of the host’s immune response.

Some of the EF-hand proteins could block “messenger” cells of the immune system from surrounding the parasite, thereby preventing the immune system from detecting their presence.

In addition, if the host launches an immune response, the EF-hand proteins could modulate the immune response to be less powerful than usual. Because of this the immune cells do not exert their full parasite-killing functions.

Lastly, some structures of the EF-hand group may be able mutate easily, and add sugars to themselves, another trick to escape being identified by the immune system.

“There is no protein in the host that has the same origin as the group of parasite proteins. This makes them more likely to become potential drug targets,” Yu says.

The computer modelling also found that the members of the group of proteins share two very stable genetic sequences. Their stability implies they can become the targets for future vaccines, say the researchers.

But Yu cautions that the functions analysed through modelling need to be validated with experimental methods.

Schistosomiasis — caused by parasitic Schistosoma worms — is found in Africa, Asia and South America. People can carry Schistosoma worms without symptoms, but in severe cases fever, fatigue, enlargement of the spleen and liver and central nervous system problems can occur.

Reference: Chinese Science Bulletin 52, 2100 (2007)