Entamoeba histolytica

Entamoeba histolytica is an anaerobic parasitic amoebozoan, part of the genus "Entamoeba". Predominantly infecting humans and other primates causing amoebiasis, "E. histolytica" is estimated to infect about 35-50 million people worldwide. "E. histolytica" infection is estimated to kill more than 55,000 people each year. Previously, it was thought that 10% of the world population was infected, but these figures predate the recognition that at least 90% of these infections were due to a second species, "E. dispar". Mammals such as dogs and cats can become infected transiently, but are not thought to contribute significantly to transmission.
The word "histolysis" literally means disintegration and dissolution of organic tissues.
Transmission.
The active (trophozoite) stage exists only in the host and in fresh loose feces; cysts survive outside the host in water, in soils, and on foods, especially under moist conditions on the latter. The infection can occur when a person puts anything into their mouth that has touched the feces of a person who is infected with "E. histolytica", swallows something, such as water or food, that is contaminated with "E. histolytica", or swallows "E. histolytica" cysts (eggs) picked up from contaminated surfaces or fingers. The cysts are readily killed by heat and by freezing temperatures, and survive for only a few months outside of the host. When cysts are swallowed they cause infections by excysting (releasing the trophozoite stage) in the digestive tract.
The pathogenic nature of "E. histolytica" was first reported by Fedor A. Lösch in 1875, but it was not given its Latin name until Fritz Schaudinn described it in 1903. "E. histolytica", as its name suggests ("histo"–"lytic" = tissue destroying), is pathogenic; infection can be asymptomatic or can lead to amoebic dysentery or amoebic liver abscess. Symptoms can include fulminating dysentery, bloody diarrhea, weight loss, fatigue, abdominal pain, and amoeboma. The amoeba can actually 'bore' into the intestinal wall, causing lesions and intestinal symptoms, and it may reach the blood stream. From there, it can reach different vital organs of the human body, usually the liver, but sometimes the lungs, brain, spleen, etc. A common outcome of this invasion of tissues is a liver abscess, which can be fatal if untreated. Ingested red blood cells are sometimes seen in the amoeba cell cytoplasm.
Risk factors.
Poor sanitary conditions are known to increase the risk of contracting amebiasis "E. histolytica". In the United States, there is a much higher rate of amebiasis-related mortality in California and Texas, which might be caused by the proximity of those states to "E. histolytica"-endemic areas, such as Mexico, other parts of Latin America, and Asia. "E. histolytica" is also recognized as an emerging sexually transmissible pathogen, especially in male homosexual relations, causing outbreaks in non-endemic regions. As such, high-risk sex behaviour is also a potential source of infection. Although it is unclear whether there is a causal link, studies indicate a higher chance of being infected with "E. histolytica" if one is also infected with HIV.
Genome.
The "E. histolytica" genome was sequenced, assembled, and automatically annotated in 2005. 
The genome was reassembled and reannotated in 2010. The 20 million basepair genome assembly contains 8,160 predicted genes; known and novel transposable elements have been mapped and characterized, functional assignments have been revised and updated, and additional information has been incorporated, including metabolic pathways, Gene Ontology assignments, curation of transporters, and generation of gene families.
The major group of transposable elements in "E. histolytica" are non-LTR retrotransposons. These have been divided in three families called EhLINEs and EhSINEs (EhLINE1,2,3 and EhSINE1,2,3). EhLINE1 encode an endonuclease (EN) protein (in addition to reverse transcriptase and nucleotide-binding ORF1), which have similarity with bacterial restriction endonuclease. This similarity with bacterial protein indicates that transposable elements have been acquired from prokaryotes by horizontal gene transfer in this protozoan parasite.
The genome of "E. histolytica" has been found to have snoRNAs with opisthokont-like features. The "E. histolytica" U3 snoRNA (Eh_U3 snoRNA) has showed sequence and structural features similar to Homo sapiens U3 snoRNA.
Pathology.
In the vast majority of cases, infection is asymptomatic and the carrier is unaware they are infected. However, in an estimated 10% of cases "E. histolytica" causes disease. Once the trophozoites are excysted in the terminal ileum region, they colonize the large bowel, remaining on the surface of the mucus layer and feeding on bacteria and food particles. Occasionally, and in response to unknown stimuli, trophozoites move through the mucus layer where they come in contact with the epithelial cell layer and start the pathological process. "E. histolytica" has a lectin that binds to galactose and N-acetylgalactosamine sugars on the surface of the epithelial cells, The lectin normally is used to bind bacteria for ingestion. The parasite has several enzymes such as pore forming proteins, lipases, and cysteine proteases, which are normally used to digest bacteria in food vacuoles but which can cause lysis of the epithelial cells by inducing cellular necrosis and apoptosis when the trophozoite comes in contact with them and binds via the lectin. Enzymes released allow penetration into intestinal wall and blood vessels, sometimes on to liver and other organs. The trophozoites will then ingest these dead cells. This damage to the epithelial cell layer attracts human immune cells and these in turn can be lysed by the trophozoite, which releases the immune cell's own lytic enzymes into the surrounding tissue, creating a type of chain reaction and leading to tissue destruction. This destruction manifests itself in the form of an 'ulcer' in the tissue, typically described as flask-shaped because of its appearance in transverse section. This tissue destruction can also involve blood vessels leading to bloody diarrhea, amebic dysentery. Occasionally, trophozoites enter the bloodstream where they are transported typically to the liver via the portal system. In the liver a similar pathological sequence ensues, leading to amebic liver abscesses. The trophozoites can also end up in other organs, sometimes via the bloodstream, sometimes via liver abscess rupture or fistulas. In all locations, similar pathology can occur.
Transcriptomic study of "E. histolytica" for promoter analysis of variable expression class of all the genes reveals that the highly transcribed genes of "E. histolytica" belongs to virulence factor genes. The study also have reported about the presence of novel downstream regulatory motifs in "E. histolytica"
Pathogen interaction.
"E. histolytica" may modulate the virulence of certain human viruses and is itself a host for its own viruses.
For example, AIDS accentuates the damage and pathogenicity of "E. histolytica". On the other hand, cells infected with HIV are often consumed by "E. histolytica". Infective HIV remains viable within the amoeba, although there has been no proof of human reinfection from amoeba carrying this virus.
A burst of research on viruses of "E. histolytica" stems from a series of papers published by Diamond "et al." from 1972 to 1979. In 1972, they hypothesized two separate polyhedral and filamentous viral strains within "E. histolytica" that caused cell lysis. Perhaps the most novel observation was that two kinds of viral strains existed, and that within one type of amoeba (strain HB-301) the polyhedral strain had no detrimental effect but led to cell lysis in another (strain HK-9). Although Mattern et al. attempted to explore the possibility that these protozoal viruses could function like bacteriophages, they found no significant changes in "Entamoeba histolytica" virulence when infected by viruses.
Pathogenesis.
"E. histolytica" causes tissue destruction which leads to clinical disease. "E. histolytica"–induced tissue damage by three main events: direct host cell death, inflammation, and parasite invasion.
Diagnosis.
Diagnosis is confirmed by microscopic examination for trophozoites or cysts in fresh or suitably preserved faecal specimens, smears of aspirates or scrapings obtained by proctoscopy, and aspirates of abscesses or other tissue specimen. A blood test is also available but is only recommended when a healthcare provider believes the infection may have spread beyond the intestine (gut) to some other organ of the body, such as the liver. However, this blood test may not be helpful in diagnosing current illness because the test can be positive if the patient has had amebiasis in the past, even if they are not infected at present.
Stool antigen detection and PCR are available for diagnosis, and are more sensitive and specific than microscopy.
Treatment.
There are a number of effective medications. Generally several antibiotics are available to treat "Entamoeba histolytica". The infected individual will be treated with only one antibiotic if the "E. histolytica" infection has not made the person sick and most likely be prescribed with two antibiotics if the person has been feeling sick. Otherwise, below are other options for treatments.
Intestinal infection:
Usually nitroimidazole derivatives (such as metronidazole) are used because they are highly effective against the trophozoite form of the amoeba. Since they have little effect on amoeba cysts, usually this treatment is followed by an agent (such as paromomycin or diloxanide furoate) that acts on the organism in the lumen.
Liver abscess:
In addition to targeting organisms in solid tissue, primarily with drugs like metronidazole and chloroquine, treatment of liver abscess must include agents that act in the lumen of the intestine (as in the preceding paragraph) to avoid re-invasion. Surgical drainage is usually not necessary except when rupture is imminent.
People without symptoms:
For people without symptoms (otherwise known as carriers, with no symptoms), non endemic areas should be treated by paromomycin, and other treatments include diloxanide furoate and iodoquinol.
There have been problems with the use of iodoquinol and iodochlorhydroxyquin, so their use is not recommended.
Diloxanide furoate can also be used by mildly symptomatic persons who are just passing cysts.
Meiosis.
In sexually reproducing eukaryotes, homologous recombination (HR) ordinarily occurs during meiosis. The meiosis-specific recombinase, Dmc1, is required for efficient meiotic HR, and Dmc1 is expressed in "E. histolytica". The purified Dmc1 from "E. histolytica" forms presynaptic filaments and catalyzes ATP-dependent homologous DNA pairing and DNA strand exchange over at least several thousand base pairs. The DNA pairing and strand exchange reactions are enhanced by the eukaryotic meiosis-specific recombination accessory factor (heterodimer) Hop2-Mnd1. These processes are central to meiotic recombination, suggesting that "E. histolytica" undergoes meiosis.
Several other genes involved in both mitotic and meiotic HR are also present in "E. histolytica". HR is enhanced under stressful growth conditions (serum starvation) concomitant with the up-regulation of HR-related genes. Also, UV irradiation induces DNA damage in "E. histolytica" trophozoites and activates the recombinational DNA repair pathway. In particular, expression of the Rad51 protein (a recombinase) is increased about 15-fold by UV treatment.