Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica

Hugo Varet,Jean-Yves Coppée,Meirav Trebicz-Geffen,Serge Ankri,Yana Shaulov,Nancy Guillen,Odile Sismeiro,Rachel Legendre

doi:10.1038/s41598-018-27086-w

Abstract

Oxidative stress is one of the strongest toxic factors in nature: it can harm or even kill cells. Cellular means of subverting the toxicity of oxidative stress are important for the success of infectious diseases. Many types of bacterium inhabit the intestine, where they can encounter pathogens. During oxidative stress, we analyzed the interplay between an intestinal parasite (the pathogenic amoeba Entamoeba histolytica - the agent of amoebiasis) and enteric bacteria (microbiome residents, pathogens and probiotics). We found that live enteric bacteria protected E. histolytica against oxidative stress. By high-throughput RNA sequencing, two amoebic regulatory modes were observed with enteric bacteria but not with probiotics. The first controls essential elements of homeostasis, and the second the levels of factors required for amoeba survival. Characteristic genes of both modes have been acquired by the amoebic genome through lateral transfer from the bacterial kingdom (e.g. glycolytic enzymes and leucine-rich proteins). Members of the leucine-rich are homologous to proteins from anti-bacterial innate immune such as Toll-like receptors. The factors identified here suggest that despite its old age in evolutionary terms, the protozoan E. histolytica displays key characteristics of higher eukaryotes’ innate immune systems indicating that components of innate immunity existed in the common ancestor of plants and animals.

Highlights

Human amoebiasis is an infectious disease caused by the amoebic parasite E. histolytica
We found that trophozoites incubated with live E. coli O55 were three times more resistant to Oxidative Stress (OS) than trophozoites incubated with heat-killed E. coli O55 or not incubated with E. coli O55 at all (Fig. 1a)
This effect was specific for H2O2 treatment, since E. histolytica incubated with live E. coli O55 were just as sensitive to the nitric oxide donor S-nitrosoglutathione (GSNO) as control trophozoites were - suggesting that E. coli O55 does not protect E. histolytica against nitrosative stress (NS) (Fig. S1)

Summary

Introduction

Human amoebiasis is an infectious disease caused by the amoebic parasite E. histolytica. The gut microbiota may significantly influence the host’s immune response and/or E. histolytica’s virulence. Invasive amoebiasis is initiated by E. histolytica’s penetration of the intestinal mucosa This amoebiasis is characterized by acute inflammation, with release of pro-inflammatory cytokines, reactive oxygen species and reactive nitrogen species from the host’s activated immune cells. These reactive species are the major cytotoxic effectors for killing E. histolytica; they oxidize and nitrosylate amoebic proteins, trigger www.nature.com/scientificreports/. Nothing is known about the influence of intestinal microbiota on the stress response in E. histolytica, i.e. whether antioxidant enzymes from bacteria might help the amoeba to defend itself against ROS. LRR proteins include cell surface factors involvement in the interactions between bacteria and human cells

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Discussion

Conclusion