Silencing of virulence genes of Entamoeba histolytica

One of Mirelman’s  main scientific interests, which was supported during the 1980’s by the Rockefeller and McArthur Foundations Program on  “ Neglected Parasitic  Diseases “, was to investigate  the virulence mechanisms of the human intestinal parasitic pathogen –Entamoeba histolytica which causes life threatening dysentery. One of his main findings was the development of a unique molecular biology method to specifically and irreversibly silence several of the virulence genes such as  the gene coding for the pore forming protein ( amoebapore) , as well as for several of the amebic proteases and lectin ( see figure ).  The resulting silenced amoebae became avirulent but grew well and did not cause any intestinal damage in Hamsters colon or liver  but still elicited an immune response . Unfortunately, due to the fact that most of the Amoebiasis patients  reside in Less developed countries with poor sanitation, Mirelman was unable to convince their Health authorities or Pharma companies to conduct oral vaccination studies with the live avirulent parasites and the project was terminated .   Ref. Transcriptional silencing of multiple genes in trophozoites of Entamoeba histolytica.  PLoS Pathog. 2006 May;2 (5) :e48.