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Gene Silencing and Overexpression to Study Pathogenicity Factors of Entamoeba histolytica

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Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology

Abstract

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. Genes encoding long-time favoured pathogenicity factors like the cysteine peptidases, the surface adherence lectins or the pore forming peptides are also present in non-pathogenic clones of the parasite. Therefore, a key task in amoebic research is to elucidate the mechanisms underlying E. histolytica invasion and tissue destruction. A lot of effort has been put into trying to identify molecules that trigger invasion of amoebae to tissues, evasion of the immune response and survival within the unfriendly environment of the host. This also applies to the genetic manipulation of parasites aiming to characterize putative pathogenicity factors. So far, the gene silencing by means of the CRISPR/Cas9 system does not work for E. histolytica. However, it has been possible to overexpress genes in E. histolytica for quite some time. In addition, a method developed in Upinder Singh’s laboratory based on RNAi silencing allows stable silencing of genes. Furthermore, E. histolytica clones with different pathogenicity are available, which were derived from the same amoeba isolate. Together with newly developed in vitro infection models, this opens up the possibility of clarifying the complex pathology of an E. histolytica infection in the future.

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This work was supported by the Jürgen Manchot Stiftung.

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König, C., Bruchhaus, I. (2020). Gene Silencing and Overexpression to Study Pathogenicity Factors of Entamoeba histolytica. In: Guillen, N. (eds) Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-44826-4_22

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