Understanding the pathogenicity of Entamoeba histolytica
Juliett Anders, Barbara Honecker, Constantin König, Ibrahim Shalabi
The pathogen Entamoeba histolytica can live asymptomatically in the human gut, or it can disrupt the intestinal barrier and induce life-threatening abscesses in different organs, most often in the liver. The molecular framework that enables this invasive, highly pathogenic phenotype is still not well understood. In order to identify factors that are positively or negatively correlated for invasion and destruction of the liver, we used a unique tool, E. histolytica clones that differ dramatically in their pathogenicity, while sharing almost identical genetic background. Based on comprehensive transcriptome studies of these clones, we identified a set of candidate genes that are potentially involved in pathogenicity. So far, using ectopic overexpression of the most promising candidates, either in pathogenic or in non-pathogenic Entamoeba clones, we identified genes where high expression reduced pathogenicity and only one gene that increased pathogenicity to a certain extend.
In this project we focus on the further characterization of the candidates by
- generation and characterization of overexpressing and silencing transfectants
- biochemical characterization of the identified candidates.
- Furthermore, to study the host response to an E. histolytica infection mice were infected with pathogenic and non-pathogenic clones, the transcriptomes of the mice liver cells were analysed and compared.
Supported by the DFG, Joachim Herz Stiftung und Jürgen Manchot Stiftung. Collaboration: Hannelore Lotter (BNITM, BH–joint PhD student)