drawn using the RASMOL program (for more information see abstract Dandekar and Leippe).
The „amoebiasis program“ was initated in 1988. It deals with a variety of aspects concerning the biology and pathogenicity of Entamoeba histolytica.
During 1996 work was continued to elucidate functions of the amoebae instrumental for pathogenic tissue invasion. One of these functions is the extraordinary capacity of E. histolytica to lyse human cells. Therefore, the underlying mechanism was further characterized, indicating that target cell death induced by E. histolytica is calcium-independent and occurs by necrosis of the cells rather than by apoptosis. In addition, the structure and function of amoebapore, the molecule considered most important for target cell lysis, was further characterized as extensively described within the investigators’ reports.
Further activities dealt with the mechanism of acquired complement resistance of E. histolytica trophozoites. Under standard culture conditions trophozoites are sensitive to human complement but acquire complement resistance upon exposure to human serum. By analysing subtractive cDNA libraries enriched for transcripts of complement resistant amoebae, a gene was identified encoding a putative ATPase. This enzyme was found to be substantially higher expressed in cells grown in the presence of human serum compared to those cultured under standard conditions.
In addition to complement resistance amoebae have to be protected against elevated levels of hydrogen peroxide (H2O2) after tissue invasion. However, this organism does not possess any catalase or peroxidase. Our recent work on the mechanism(s) that enable E. histolytica trophozoites to inactivate H2O2 resulted in the identification of an unusual amoeba protein, which is capable to remove H2O2 in the presence of a second amoeba molecule. Obviously, the latter is required as a hydrogen donor.
An important step towards functional genetics in E. histolytica was the adaptation of a tetracyclin inducible vector system that allows precisely controlled expression of genes introduced into the amoebae.
Progress was also made in the development of an amoebiasis vaccine.
An epitope on the 170-kDa amoeba lectin was identified comprising just
25 amino acid residues able to confer antibody mediated resistance against
Privatdozent Dr. Egbert Tannich, Molecular Biology (Coordinator)