Entamoeba histolytica - Pathogenesis, Virulence factors
Pathogenesis of Entamoeba histolytica
Entamoeba histolytica and E. dispar are morphologically similar but can be differentiated using RNA probes, DNA probes, and monoclonal antibodies.
Entamoeba histolytica are pathogenic strain while E. dispar is a non-pathogenic strain as they lack the capacity to invade tissue and is associated with an asymptomatic carrier state.
The pathogenesis of Entamoeba histolytica depends on its ability to:
agglutinate the lectin, Concavalin A
caecal ulceration in weaning rats
increase the phagocytosis of RBCs
adhere to the apical epithelial cells
production of isoenzyme patterns (zymodemes) on starch-gel electrophoresis
Entamoeba histolytica trophozoites can infect almost all tissues of the human body including intestinal mucosa and liver. In extreme cases, this parasite form can even infect the brain, skin, bone as well as cartilage.
Intestinal and extra-intestinal amoebiasis by Entamoeba histolytica occurs through the following stages:
Colonization of the large intestine
Adherence of Entamoeba histolytica to the colon and lysis of mucosal cells
Invasion of the intestinal mucosa
Extra-intestinal invasion of tissue or serum
Colonization of the large intestine
Colonization of the large intestine is the first stage of amoebic infection
the caecum and sigmoid colon’s content moves in a very slow fashion which facilitates the invasion by the amoebae as it comes in contact with the colonic mucosa for an extended period of time
in addition, the presence of normal gut bacteria in the colon is a necessary metabolic environment.
Adherence of Entamoeba histolytica to the colon and lysis of mucosal cells
following colonization, the parasite induces an increased secretion of the mucus and changes its composition to mucocin which in turn makes the colon epithelial cells more susceptible to invasion.
the lectin present in Entamoeba histolytica trophozoites helps in adherence to the epithelial cells, mucins of the colon as well as leucocytes.
after adherence on the host colon cells with the help of ionophore-like protein, the trophozoites lyses the cells which cause the leakage of ions such as Na+, K+, and Ca+ from the target cell cytoplasm
Invasion of the intestinal mucosa
The Entamoeba histolytica invasion begins at the intergranular site of the intestinal mucosa
the invading amoebae produce the extra-cellular enzyme called cysteine kinase which causes the proteolytic destruction of the host tissue.
The enzyme functions by digesting the extra-cellular matrix and breaking down IgA molecules which minimizes certain components of the complement system
host’s polymorphonuclear response and also further damages the host tissues.
the tissue destruction is seen as flask-shared amoebic ulcers which are the typical pathognomonic of amoebiasis in the intestine.
Extra-intestinal invasion of tissue or serum
in some cases, extra-intestinal invasion of tissue or serum occurs. The Entamoeba histolytica trophozoites are carried by the portal blood circulation to the liver from where they can further disseminate to other organs such as the lungs, heart, spleen, brain, and stomach
the enzyme cysteine proteinase helps the amoeba to evade the complement-mediated lysis in the bloodstream and other organ tissues.
* cysteine proteinase functions by activating the complement system by clearing C3 or by quickly breaking down C3a and anaphylatoxin, which results in the limitation of host inflammatory response.
As the infection progresses, in the liver it produces an abscess filled with acellular proteinaceous pus. In addition to the lysis of neutrophils and hepatocytes by the amoebae, neutrophil toxin also contributes to the necrosis of hepatocytes.
Virulence factors of Entamoeba histolytica
The virulence factors of Entamoeba histolytica include:
Amoebic lectin
Ionophore-like protein
Hydrolytic enzymes
Toxins and hemolysins
Amoebic lectin
measures 260 kD (kilodalton)
is a surface protein called galactose-inhibitable adherence lectin
composed of two sub-units- 170 kD subunit and 35 kD subunit
the 170 kD subunit, which is rich in cysteine, contains a short cytoplasmic domain as well as a toxin membrane domain.
Its function is to adhere the trophozoites to galactose receptors present in the intestinal mucosa. It also protects Entamoeba histolytica from the host complement system by preventing the complement system’s adherence to its surface.
functions by mediating the adherence of Entamoeba histolytica to the intestinal mucosa
Ionophore-like protein
from the target host cell, it works by leaking ions such as Na+, K+, Ca+
Hydrolytic enzymes
hydrolytic enzymes cause proteolytic destruction of the tissue
includes hydrolytic enzymes such as phosphatase, proteinases, glycosidase, RNAse