Entamoeba histolytica under Oxidative Stress: What Countermeasure Mechanisms Are in Place?

Abstract

Entamoeba histolytica is the causative agent of human amoebiasis; it affects 50 million people worldwide and causes approximately 100,000 deaths per year. Entamoeba histolytica is an anaerobic parasite that is primarily found in the colon; however, for unknown reasons, it can become invasive, breaching the gut barrier and migrating toward the liver causing amoebic liver abscesses. During the invasive process, it must maintain intracellular hypoxia within the oxygenated human tissues and cellular homeostasis during the host immune defense attack when it is confronted with nitric oxide and reactive oxygen species. But how? This review will address the described and potential mechanisms available to counter the oxidative stress generated during invasion and the possible role that E. histolytica's continuous endoplasmic reticulum (Eh-ER) plays during these events.

Keywords: Entamoeba histolytica; endoplasmic reticulum; energetic metabolism; nitric oxide; oxidative stress.

Figure 1

Schematic representation of the glycolytic pathway in E. histolytica. The diagram depicts the pathways that are present under (A) microaerophilic control conditions or (B) after exposure to reactive oxygen species (ROS) or nitric oxide (NO) (in red). The thickness of the arrows represents the relative flux rates through the enzymatic reactions. The size of the metabolite abbreviation represents its relative concentration within the trophozoites. Under stress condition, pyruvate:ferredoxin oxidoreductase (PFOR) and aldehyde/alcohol dehydrogenase (ADHE) (in blue) are inhibited. The metabolic intermediaries before PFOR and ADHE reactions (in green) are accumulated with the concomitant decrease in ethanol (EtOH) and adenosine triphosphate (ATP) production. Glc_out, external glucose; Glc_in, internal glucose. Adapted from [47].

Figure 2

Schematic representation of the main components of the E. histolytica endomembrane network that is present in a trophozoite in the absence (−) or presence (+) of oxidative stress (OS). The diagram shows the described effects upon OS: ER fragmentation [22], a loss of adherence capacities of the Gal/GalNAc lectin [63], and a modification in the cytoskeleton proteins that could impair its function [64]. Notably, endocytic and exocytic activities remain functional under OS exposure. The effect of OS in the retromer complex, the TGN, and the structure of the mitosomes is unknown.