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Silence Of The Amoebae: Scientists Render A Disease-causing Pathogen Harmless

Freedom of expression is great, but silence is golden -- at least when it comes to amoebae, which are intestine-dwelling parasites that cause life-threatening dysentery in many parts of the world.

Three years ago, scientists at the Weizmann Institute accidentally discovered a way to silence the expression of a key amoebic gene, one which codes for a toxic protein that kills human intestinal cells infected with this devastating illness. Now the scientists have developed a way to successfully silence the expression of two additional virulence genes in the same amoebae.

Rivka Bracha and colleagues in the lab of Prof. David Mirelman in the Biological Chemistry Department had shown that expression of the gene coding for the toxic protein could be prevented by inserting a plasmid (a small loop of DNA) containing a copy of a specific part of that gene into the amoeba cell nucleus. Introducing the plasmid led to the modification of DNA "packing" proteins, causing the DNA-protein packages to become more tightly coiled -- something like a tangled telephone cord -- and causing an irreversible silencing of gene expression. In a recent paper published in PLoS Pathogens, the Weizmann scientists report the silencing of two additional virulence genes in the same amoebae using a similar plasmid-induced principle.

The disabled amoebae, though rendered harmless, still display the same repertoire of surface antigens (markers recognized by the immune system) as the disease-causing strain. The scientists now plan to test the ability of these silenced amoebae to serve as a live vaccine by evoking an intestinal immune response. If successful, it may put an end to amoebic diseases that claim the lives of thousands yearly and afflict millions more.

Prof. David Mirelman's research is supported by the M.D. Moross Institute for Cancer Research; Mrs. Erica A. Drake, Scarsdale, NY; Mr. and Mrs. Henry Meyer, Wakefield, RI; and the late Claire Reich, Forest Hills, NY. Prof. Mirelman is the incumbent of the Besen-Brender Chair of Microbiology and Parasitology.

Source: Weizmann Institute of Science. August 2006.