Identification of the Virulence Landscape Essential for Entamoeba histolytica Invasion of the Human Colon

Abstract

Entamoeba histolytica is the pathogenic amoeba responsible for amoebiasis, an infectious disease targeting human tissues. Amoebiasis arises when virulent trophozoites start to destroy the muco-epithelial barrier by first crossing the mucus, then killing host cells, triggering inflammation and subsequently causing dysentery. The main goal of this study was to analyse pathophysiology and gene expression changes related to virulent (i.e. HM1:IMSS) and non-virulent (i.e. Rahman) strains when they are in contact with the human colon. Transcriptome comparisons between the two strains, both in culture conditions and upon contact with human colon explants, provide a global view of gene expression changes that might contribute to the observed phenotypic differences. The most remarkable feature of the virulent phenotype resides in the up-regulation of genes implicated in carbohydrate metabolism and processing of glycosylated residues. Consequently, inhibition of gene expression by RNA interference of a glycoside hydrolase (β-amylase absent from humans) abolishes mucus depletion and tissue invasion by HM1:IMSS. In summary, our data suggest a potential role of carbohydrate metabolism in colon invasion by virulent E. histolytica.

Author Summary

Entamoeba histolytica is an intestinal parasite which displays diverse phenotypes with respect to pathogenesis in the human colon. Trophozoites can remain as commensal, without causing evident intestinal damage, or they can destroy the colonic mucosa leading to amoebiasis. Using human colon explants and transcriptome analysis, we investigated the gene expression profile of two E. histolytica strains (virulent and non-virulent) during their contact with the intestinal mucus to gain insights into the molecular basis responsible for amoebic divergent phenotypes. Our results suggest that the virulent E. histolytica, when in contact with the intestinal barrier, specifically increases the rate of gene transcription for enzymes necessary to exploits the carbohydrate resources present in the human colon. Using RNA interference methodologies to knockdown gene expression, our data revealed the potential role of amoebic β-amylase (a glycosydase) in colon invasion and mucus depletion. Our data implies that the ability of an E. histolytica strain to exploit the carbohydrate resources might affect its ability to invasion the intestine.