Utilization of Different Omic Approaches to Unravel Stress Response Mechanisms in the Parasite Entamoeba histolytica

Abstract

During its life cycle, the unicellular parasite Entamoeba histolytica is challenged by a wide variety of environmental stresses, such as fluctuation in glucose concentration, changes in gut microbiota composition, and the release of oxidative and nitrosative species from neutrophils and macrophages. The best mode of survival for this parasite is to continuously adapt itself to the dynamic environment of the host. Our ability to study the stress-induced responses and adaptive mechanisms of this parasite has been transformed through the development of genomics, proteomics or metabolomics (omics sciences). These studies provide insights into different facets of the parasite's behavior in the host. However, there is a dire need for multi-omics data integration to better understand its pathogenic nature, ultimately paving the way to identify new chemotherapeutic targets against amebiasis. This review provides an integration of the most relevant omics information on the mechanisms that are used by E. histolytica to resist environmental stresses.

Keywords: Entamoeba histolytica; glucose starvation; iron starvation; microbiota; nitrosative stress; omics; oxidative stress; virulence.

Figure 1

Strategies used by E. histolytica when challenged with different stresses. E. histolytica faces threat in a number of ways: 1. Following colonic invasion, trophozoites penetrate the intestinal epithelial layer of the host where they are challenged by immune cell during invasion. Exposure to ROS (Rastew et al., 2012) and RNS (Kolios et al., 2004) released by macrophages and other immune cells eventually triggers the parasite defense mechanisms as shown in the box. 2. The amoeba is also threatened by low glucose concentration in the colon and it survives this condition by inhibiting glycolysis and by degrading stored glycogen and converting it to free glucose. Moreover, low glucose concentration triggers the parasite to become more virulent by upregulating Gal/GalNAc lectins (Baumel-Alterzon et al., 2013). 3. Changes occurring during the absence of L-cysteine, which is an important thiol required for antioxidant activity in the parasite. During cysteine starvation, there is an increase of phospholipids and other metabolites such as S-methyl cytosine, S-adenosine methionine etc. (Jeelani et al., 2014). 4. The absence of iron also increases virulence of the parasite by increasing the expression of CP-A5, CP-A7, and leads to the upregulation of transport proteins to scavenge iron from other external sources (Hernandez-Cuevas et al., 2014). SOD, superoxide dismutase; CLS, cyst like structure; NAOD, N-acetyl ornithine deactylase; Gal/GalNAc, Galactose/N-acetylgalactosamine binding lectin; CP, cysteine proteinases; DPD, dihydropyramidine dehydrogenase; AIG, Androgen Inducible Gene; ABC transporters; ATP, binding cassette transporters.

Figure 2

General principle of stress response in eukaryotic cells and E. histolytica. When a cell is exposed to stress, there is an activation of a stress-responsive protein (De Nadal et al., ; Walter and Ron, ; Smith and Workman, 2012), which induces signal transduction mediated by protein phosphorylation (Darling and Cook, ; Sharma et al., 2016). The stress signal is then transferred to downstream effector proteins. These stress responses generally lead to inhibition of cap-dependent translation initiation and consequent suppression of general protein synthesis. Stress responses also lead to additional changes, involving modulation of gene expression, cell proliferation, cell survival, and changes in metabolism (Lopez-Maury et al., 2008). Hsps, Heat shock proteins; eIF2, Eukaryotic Intitation Factor 2; MAPK, Mitogen Activated Protein Kinases.