Entamoeba

Abstract

Entamoeba histolytica is an obligate human intestinal parasite causing amoebic dysentery and liver abscess. Entamoeba dispar is its close largely nonpathogenic relative. Both species are well adapted to the human host. The motile amoebae called trophozoites dwell in the lumen of the large intestine; in its distal part, they differentiate to cysts, which are excreted and can survive in the environment and infect new hosts. Although metronidazole and other nitroimidazoles represent an efficient treatment, there are more than 55,000 deaths worldwide every year.

The E. histolytica genome project led to a better understanding of the molecular equipment; two surprises were the significant number of genes acquired from bacteria by lateral gene transfer and a very high number of protein kinases and phosphatases underscoring the complex signal transduction pathways in this parasite.

The parasite attacks human cells by first attaching to them via a galactose and N-acetylgalactose (Gal/GalNAc)-specific lectin. The host cell membrane is pierced by a pore-forming protein called amoebapore, and cysteine proteinases destroy cellular components, antibodies and complement.

The human host mounts a massive humoral and cellular immune response against E. histolytica with macrophages and NKT cells being the most efficient defenders. The antibody response is limited in its impact through the ability of the amoebae to cap and shed antibodies bound to their surface. In addition, E. histolytica has developed a number of mechanisms to cope with immune cells.

E. histolytica belongs to the microaerophilic microorganisms devoid of classical mitochondria and devoid of oxidative phosphorylation. So the main pathway to extract energy is by glycolysis, and when not needed, the energy is stored in the form of glycogen. The biosynthetic abilities are quite crippled; most useful molecules, sugars, amino acids, lipids and nucleotides are acquired from the host or from phagocytosed bacteria.