Extensive transcriptome analysis correlates the plasticity of Entamoeba histolytica pathogenesis to rapid phenotype changes depending on the environment.

Christian Weber,Marie-Agnes Dillies,Hugo Varet,Nancy Guillén,Cesar Lopez-Camarillo,Jean Yves Coppée,Mikael Koutero,Chung-Chau Hon

doi:10.1038/srep35852

Christian Weber, Marie-Agnes Dillies + Show 6 more

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https://doi.org/10.1038/srep35852

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Abstract

Amoebiasis is a human infectious disease due to the amoeba parasite Entamoeba histolytica. The disease appears in only 20% of the infections. Diversity in phenotypes may occur within the same infectious strain in the gut; for instance, parasites can be commensal (in the intestinal lumen) or pathogenic (inside the tissue). The degree of pathogenesis of clinical isolates varies greatly. These findings raise the hypothesis that genetic derivation may account for amoebic diverse phenotypes. The main goal of this study was to analyse gene expression changes of a single virulent amoebic strain in different environmental contexts where it exhibit different degrees of virulence, namely isolated from humans and maintained through animal liver passages, in contact with the human colon and short or prolonged in vitro culture. The study reveals major transcriptome changes in virulent parasites upon contact with human colon explants, including genes related to sugar metabolism, cytoskeleton rearrangement, stress responses and DNA repair. Furthermore, in long-term cultured parasites, drastic changes in gene expression for proteins with functions for proteasome and tRNA activities were found. Globally we conclude that rapid changes in gene expression rather than genetic derivation can sustain the invasive phenotype of a single virulent isolate of E. histolytica.

Highlights

Especially with trophozoite virulence[5]
The marks associated with virulence and intestinal invasion are lost in virulence-attenuated amoebae, which appeared highly active in proteasome activities and repressed in tRNA transfer enzymes
The RNA libraries were constructed from polyA +mRNA from the HM1:IMSS strain grown in four different conditions (Fig. 1A) Virulent parasites extracted from liver abscesses of infected hamsters (Vir), B) Virulent parasites exposed to explants of human colon (VirColon), C) long-term cultured virulence-attenuated amoeba (ATT) that have lost the ability to form liver abscesses and D) trophozoites short-time cultured (Normal Culture) for roughly lest than three months (24 passages)

Summary

Introduction

Especially with trophozoite virulence[5]. The amoebic invasive process can induce an inflammatory response accompanied by disease-relevant cell death (for a review[6]). The data obtained revealed important regulatory networks involved in strain phenotype differences[10,11,12], colonic and hepatic invasion[12,13,14,15], responses to stress[16,17], drug treatments[18,19], metabolic changes[20,21,22,23] and the encystation process[24] Overall, these studies have identified diverse pathogenic factors, new pathways for drug treatment and some elements of transcriptional gene regulation. In this work we hypothesized that for a given E. histolytica strain, changes in the environment (in particular those occurring during the interaction with the human host) trigger the major gene expression marks related to different degrees of virulence To test this hypothesis, we applied high-throughput RNA sequencing to profile, for the first time, samples from the same isolate (HM1:IMSS) in contact with different environments. Based on our results we concluded that rapid and highly specific changes in the amoebic transcriptome, rather than genetic variation of the amoeba isolate, can account for the invasion of human colon by virulent E. histolytica

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