Gene Activator Protein May Be Key to Controlling Schistosomiasis

Parasitologists have identified a gene activator protein in Schistosoma mansoni that spurs development of the parasite after infection of its human host and is an attractive target for a new generation of drugs to control this disease.

Schistosome parasites infect more than 200 million people worldwide and cause human schistosomiasis. Free-swimming schistosome larvae are highly mobile, and invade and penetrate the host's skin to perpetuate their lifecycle in their human host, growing from 90-215 µm in length as a schistosomulum to a 7-20 mm long adult worm. Few molecular pathways have been identified in schistosome worms that are important for parasite early development.

In the current study, investigators at Case Western Reserve University (Cleveland, OH, USA) focused on the gene activator protein myocyte enhancer factor 2 protein (Mef2). This protein a major regulator of muscle and nerve development in mammals and insects and is highly conserved from bread yeast to vertebrates.

They reported in the January 3, 2012, online edition of the journal PLoS Neglected Tropical Diseases that quantitative PCR demonstrated that Mef2 was expressed during several stages of schistosome development, and that it could bind to conserved Mef2 DNA consensus binding sequences. SmMef2 was shown to be a transactivator that could induce transcription of four separate heterologous reporter genes by yeast one-hybrid analysis.

The intent is to seek out drugs to target SMfe2. Although Mef2 is present in humans, the portion of SMef2 that switches on gene activity is so different from human Mef2 that it should be possible to target that part, and not affect the host.

“This is really a disease of poor people," said senior author Dr. Emmitt Jolly, professor of biology at Case Western Reserve University. “The strategy to combat the disease cannot be expensive.”

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