The Parasites

Entamoeba histolytica is a protozoan parasite which predominantly infects humans and other primates and causes amebiasis. The parasite has two stages in its life cycle, the trophozoite and the cyst. The trophozoite, an active and motile form, is responsible for pathogenicity while the cyst, a semi-dormant form with hardy structure, is the infective form. E. invadens, a protozoan parasite of reptiles, also causes amebiasis in reptiles similar to that of E. histolytica in humans. Since E. histolytica does not encyst efficiently in axenic culture, E. invadens has been used as a model to study encystation and also excystation since it can be induced to form cysts under axenic conditions.

The Diseases

E. histolytica is estimated to infect about 50 million people worldwide and amebiasis is estimated to cause 70,000 deaths per year. Two major forms of amebiasis are amebic dysentery and amebic liver abscess. Metronidazole is the most effective drug for therapy of invasive amebiasis.

Life Cycle of E. histolytica

Ingested mature cysts in contaminated food and water undergo excystation in the small intestine. The hatched metacystic ameba divides to produce eight trophozoites and they migrate to the large intestine and establish a colony by multiplication. Encystation follows as part of the normal course of the life cycle as trophozoites move down the colon toward the anus. Invasion of the intestinal mucosa by trophozoites results in the formation of ulcers. Occasionally, trophozoites migrate to various organs of the body through the bloodstream. The most common extraintestinal site is the liver. In rare cases secondary spread occurs to the lung, brain and skin.

Studies on Entamoeba encystation and excystation

We have investigated to elucidate mechanism of Entamoeba encystation and excystation using an axenic culture system in vitro of E. invadens. Experiments with several inhibitors demonstrated involvement of actin cytoskeleton, signaling molecules such as PKC and PI3K, calcium ions/calmodulin and proteasomes in these processes. We have recently demonstrated the involvement of serine proteases in the excystation and metacystic development of E. invadens. We have identified three families of serine proteases in this parasite, and have confirmed an increase in the expression level of those proteases in cysts after induction of excystation.