Entamoeba histolytica – Model Minimalist

Efficiency is defined as the ability to accomplish a job with the minimum expenditure of time and effort.  Like a hybrid car that doesn’t need gas, Entamoeba histolytica survives in harsh, low-nutrient environments with half the number of the energy pathways that most other eukaryotes use to generate energy.  Unlike most eukaryotes, E. histolytica solely relies upon glycolysis and fermentation for energy and does not use the TCA cycle or the michochondrial electron transport chain reactions to generate ATP.  While this may not seem very efficient, lowering the number of proteins needed to be made for metabolism is efficient, especially since parasites are renowned for living off of the host’s energy supply.  Not only are E. histolytica’s metabolic mechanisms efficient in the parasitic sense, but they are apparently quite effective, as E. histolytica’s virulence actually increases during glucose starvation (2).

Figure 1. The above figure shows the lifecycle of
Entamoeba histolytica, the causative agent of amoebiasis.
The derivation of trophozoites from cysts via excystation
is shown in the bottom portion of the figure.

Amoebiasis is a disease common in tropical areas and countries with low sanitation standards.  In areas of inadequate sanitation, amoebiasis is commonly spread via the consumption of food and water contaminated with spores of the unicellular eukaryote E. histolytica; which are passed in feces. It is estimated that only about 10-20% of people infected with E. histolytica will develop symptoms. Although not normally deadly, in some cases amoebiasis results in liver abscesses and ulceration of the intestinal mucosa.  Amoebiasis due to E. histolytica is most common in humans, and reports of infection in animals are rare (3).

E. histolytica infection begins when a spore is ingested.  From there, E. histolytica active and virulent trophozoites arise via excystation from the ingested, inactive spores in the small intestine (see Figure 1 for a diagram of excystation). This amoeba then takes up residence in the small intestine where the concentration of glucose is low, at about 1%. At this point, E. histolytica can continue on to the large intestine where infectious spores can form and be passed in the feces.  In the large intestine trophozoites are able to multiply via binary fission. This parasite can also invade the intestinal mucosa causing intestinal disease or can enter the bloodstream to proceed to infect the liver or brain (1). Invasion of the intestinal mucosa is perpetuated by the small peptides called amoebapores that E. histolytica secretes, which are capable of forming pores in lipid bilayers. Also involved in E. histolytica’s invasiveness are its cysteine proteinases which help to facilitate tissue penetration by trophozoites by disrupting the intestinal mucus. In the bloodstream E. histolytica has the ability to phagocytose red blood cells.

Oddly, E. histolytica’s virulence actually increases during periods of glucose starvation (2). While most organisms either respond to stress by admitting temporary defeat (spore formation) or by gaining weight and wrinkles (humans), E. histolytica thrives under stress like an Olympian. Instead of up-regulating common stress proteins such as heat-shock proteins as many eukaryotes do in a stressful environment, E. histolytica differentially up-regulates those proteins involved in protein synthesis such as the 60S and 40S subunits of the ribosome. This means that in response to stress, E. histolytica starts assembling and gathering its army to fight. This amoeba has been shown to respond to glucose starvation via doubling hemolytic activity and increasing cytopathic activity, thus becoming an even more threatening enemy. Tovy et al. (2011) also showed that migration of the trophozoite form of E. histolytica through 8µm pores also increased, as did cell binding by the amoeba, which is important for tissue penetration and invasion. Unlike humans who are known to gain weight due to stress, E. histolytica up-regulates the proteins involved with metabolism, specifically those involved in the fatty acid degradation pathway. Thus, unlike the average human, normally paralyzed by stressful environments, E. histolytica is adept at surviving and thriving under stressful conditions. Don’t you wish your response to stress was to immediately shed your fat stores, too?

Not only is E. histolytica extremely well-adapted metabolically for stressful nutrient-poor environments, but it is also highly motile.  Motility has historically been linked to virulence since this enables the parasite to seek out additional nutrients which normally results in the invasion of nearby tissues. This amoeba contains an anterior pseudopodia as well as a posterior appendage called a uroid.  The EhPAK protein, a member of the p21-activated kinase family, has been linked to the motility and phagocytic ability of E. histolytica. EhPAK is found highly concentrated in the pseudopod in addition to being found somewhat throughout the organism.  It is believed that this protein is involved in the actin-myosin cytoskeleton dynamics which make E. histolytica such a motile microbe, able to invade the liver and cause abscesses.

Whether the physically visible structures of E. histolytica such as its pseudopodia and uroid are more advanced than its minimalistic metabolic organization can be left for others to debate.  It is however indisputable that E. histolytica is one of the most unique eukaryotes in our world.

L.A.

References:
1. Estrada-Figueroa, L.A., Y. Ramirez-Jimenez, C. Osorio-Trujillo, M. Shibayama, F. Navarro-Garcia, C. Garcia-Tovar, and P. Talamas-Rohana. 2011. “Absence of CD38 delays arrival of neutrophils to the liver and innate immune response development during hepatic amoebiasis by Entamoeba histolytica”. Parasite Immunology (Accepted Article).

2. Tovy A, Hertz R, Siman-Tov R, Syan S, Faust D, et al. 2011. “Glucose Starvation Boosts Entamoeba histolytica Virulence”. PLoS Negl Trop Dis 5(8): e1247.

3. http://www.cdc.gov/parasites/amebiasis/biology.html