Date of Award
Doctor of Philosophy (PhD)
Entamoeba histolytica is a water- and food-borne intestinal protozoan parasite that causes amoebiasis and liver abscess and is responsible for symptomatic disease in approximately 100 million people each year leading to ~ 100,000 deaths. The most common disease transmission follows the oral-fecal route, but it can also be transmitted by mechanical vectors such as animals carrying the amoeba from contaminated sources to water systems. In rare cases, disease transmission has been recorded in some patients in which men-to-men sexual practices were preferred.
The life cycle of E. histolytica starts through ingestion of infectious cysts, which are non-dividing, quadri-nucleated structures surrounded by a chitinous cell wall. The chitin cell wall protects the cyst from damage, including the harsh acidic environment of the stomach. Once the cyst enters the nutrient-rich duodenum of the small intestine, excystation takes place to produce proliferative trophozoites. Trophozoites, the motile disease-causing form of E. histolytica, move along the digestive tract and then colonize the large intestine. Trophozoites must encyst back to cysts to survive outside of the host body, so their life cycle requires both successful encystation and excystation.
Over the decades, Entamoeba invadens, a related species that is a pathogen of reptiles, has been used as a model to study encystation and excystation because the E. histolytica life cycle could not be replicated in the laboratory. Even though the disease ranked as the third most common cause of death from parasitic infections with a significant global burden, it is consequently less well studied. These two species do not share a high genome sequence identity, and humans and reptiles provide very different host environments, limiting the applicability of E. invadens findings to E. histolytica. Our research group (Wesel et al., (2021)) recently established a means for in vitro encystation of E. histolytica in axenic culture, allowing us now to study encystation and excystation directly in the human parasite. E. histolytica encystation is induced by nutrient starvation with high cell density, and the resulting cysts displayed the four defining cyst characteristics: detergent resistance, a chitinous cell wall, small round cell morphology, and tetranucleation.
In this dissertation, I further examined the processes of encystation and excystation in E. histolytica. The heat stress response and encystation overlap in Entamoeba, and here I have investigated the effect of heat stress on encystation to better understand the intersection of the general stress response and encystation. I also examined the signals that induce excystation of non-motile cysts back to motile and actively proliferating trophozoites. These studies will lead to a better understanding of the life cycle of E. histolytica, its infection mechanisms, and potential drug targets.
Bastuzel, Irem, "Heat Stress Response and Excystation in Entamoeba histolytica" (2022). All Dissertations. 3132.
Author ORCID Identifier
Available for download on Thursday, August 31, 2023