
''Entamoeba histolytica'' is an
anaerobic parasitic
amoebozoa
Amoebozoa is a major Taxonomy (biology), taxonomic group containing about 2,400 described species of Amoeba, amoeboid protists, often possessing blunt, fingerlike, Pseudopod#Morphology, lobose pseudopods and tubular mitochondrial cristae. In trad ...
n, part of the
genus
Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
''
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
A trophozoite (G. ''trope'', nourishment + ''zoon'', animal) is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing ''Plasmodium falciparum'' and those of the ''Giardia'' group. The complementary form of the t ...
) stage exists only in the host and in fresh loose feces;
cyst
A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubb ...
s 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; they 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
Fritz Richard Schaudinn (19 September 1871 – 22 June 1906) was a German zoologist.
Born in Röseningken (now in Ozyorsky District) in the Province of Prussia, he co-discovered, with Erich Hoffmann in 1905, the causative agent of syphilis, ' ...
described it in 1903. ''E. histolytica'', as its name suggests (''histo''–''lytic'' = tissue destroying), is
pathogenic
In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.
The term ...
; infection can be asymptomatic, or it can lead to
amoebic dysentery
Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba '' Entamoeba histolytica''. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, coloni ...
or amoebic
liver abscess
A liver abscess is a mass filled with pus inside the liver. Common causes are abdominal conditions such as appendicitis or diverticulitis due to haematogenous spread through the portal vein. It can also develop as a complication of a liver injury.
...
.
[ ] Symptoms can include fulminating dysentery, bloody diarrhea, weight loss, fatigue, abdominal pain, and
amoeboma. The amoeba can 'bore' into the intestinal wall, causing
lesion
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals.
Types
There is no de ...
s and intestinal symptoms, and it may reach the bloodstream or peritoneal cavity.
From there, it can reach vital organs of the human body, usually the liver, but sometimes the lungs, brain, and spleen. A common outcome of this invasion of tissues is a liver abscess, which can be fatal if untreated.
[ Ingested ]red blood cell
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s 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 (this might be caused by the proximity of those states to ''E. histolytica''-endemic areas, such as Mexico), 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 human immunodeficiency virus
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of th ...
(HIV).
Genome
The ''E. histolytica'' genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
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 encodes an endonuclease (EN) protein (in addition to reverse transcriptase and nucleotide-binding ORF1), which has similarity with bacterial restriction endonuclease
A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class o ...
. This similarity with bacterial protein indicates that transposable elements have been acquired from prokaryotes by horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...
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 shown sequence and structural features similar to Homo sapiens U3 snoRNA.
Pathogen interaction
''E. histolytica'' may modulate the virulence of certain human viruses and is itself a host for its own viruses.
For example, acquired immunodeficiency syndrome (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.
Immunopathogenesis
''E. histolytica'' causes tissue destruction which leads to clinical disease. ''E. histolytica'' induces tissue damage by three main events: direct host cell death, inflammation, and parasite invasion. 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
Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of glycoconjugates an ...
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 the intestinal wall and blood vessels, sometimes onto the 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 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 the transverse section. This tissue destruction can also involve blood vessels leading to bloody diarrhea, and 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 fistula
In anatomy, a fistula (: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") is an abnormal connection (i.e. tube) joining two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other h ...
s. Similarly, when the trophozoites travel to the brain, they can cause amoebic brain abscesses.
Diagnosis
Diagnosis is confirmed by microscopic examination for trophozoites or cysts in fresh or suitably preserved fecal specimens, smears of aspirates or scrapings obtained by proctoscopy, and aspirates of abscesses or another tissue specimen. A blood test is also available, but it is recommended only when a healthcare provider believes the infection may have spread beyond the intestine to some other organ of the body, such as the liver. However, this blood test may not help diagnose current illness, because the test can be positive if the patient has had amebiasis in the past, even if they are not infected at the time of the test.
Stool antigen detection and PCR are available for diagnosis, and are more sensitive and specific than microscopy.
Entamoeba histolytica.jpg, ''Entamoeba histolytica'' trophozoite
A trophozoite (G. ''trope'', nourishment + ''zoon'', animal) is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing ''Plasmodium falciparum'' and those of the ''Giardia'' group. The complementary form of the t ...
File:Amoebic Ulcer Intestine.jpg, Amoebic intestinal ulcer
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughin ...
caused by ''E. histolytica''
File:Trophozoites of Entamoeba histolytica with ingested erythrocytes.JPG, Trophozoites of ''E. histolytica'' with ingested erythrocyte
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...
s
File:Entamoeba histolytica 01.jpg, ''E. histolytica'' cyst
A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubb ...
File:Ehistdisp cyst wtmt.jpg, Immature ''E. histolytica'' cyst (mature cysts have four nuclei)
File:Entamoeba histolytica quadrinucleate cyst.jpg, ''E. histolytica'' quadrinucleate cyst with chromatoid bodies.
File:Entamoeba histolytica binary fission.jpg, Multiplication by binary fission
File:Entamoeba hystolytica.jpg, ''E. histolytica'' drawing
File:Immunohistochemical staining of trophozoites (brown) using specific anti–Entamoeba histolytica macrophage migration inhibitory factor antibodies in a patient with amebic colitis.jpg, Immunohistochemical staining of trophozoites (brown) using specific anti–''Entamoeba histolytica'' macrophage migration inhibitory factor antibodies in a patient with amebic colitis
Treatment
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 will most likely be prescribed two antibiotics if the person has been feeling sick. Otherwise, below are other options for treatments.
Intestinal infection
Usually nitroimidazole
Nitroimidazoles are the group of organic compound, organic compounds consisting of an imidazole ring with at least one nitro group substituent. The term also refers to the class of antibiotics that have nitroimidazole in their structures. These an ...
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
A cyst is a closed Wikt:sac, sac, having a distinct Cell envelope, envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac ...
, 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
Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...
and chloroquine
Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of heme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. Certain types ...
, 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
People without symptoms, otherwise known as asymptomatic carriers, in non-endemic areas, should be treated with paromomycin; 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 eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s, homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
(HR) ordinarily occurs during meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
. The meiosis-specific recombinase
Recombinases are genetic recombination enzymes.
Site specific recombinases
DNA recombinases are widely used in multicellular organisms to manipulate the structure of genomes, and to control gene expression. These enzymes, derived from bacteria ( ...
, Dmc1, is required for efficient meiotic HR, and Dmc1 is expressed in ''E. histolytica''. The purified Dmc1 from ''E. histolytica'' forms presynaptic
In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
filaments and catalyzes ATP-dependent homologous DNA pairing and DNA strand exchange over at least several thousand base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s. 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
DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to t ...
protein (a recombinase
Recombinases are genetic recombination enzymes.
Site specific recombinases
DNA recombinases are widely used in multicellular organisms to manipulate the structure of genomes, and to control gene expression. These enzymes, derived from bacteria ( ...
) is increased about 15-fold by UV treatment.[
]
See also
* List of parasites (human)
References
External links
''Entamoeba histolytica'' image library
''Entamoeba histolytica''
– Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
* CDC
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
br>''DPDx Parasitology Diagnostic Web Site''
* LSHTMbr>''Entamoeba'' Homepage
''Entamoeba'' Genome Resource
– AmoebaDB
''Entamoeba histolytica'' article
from the US Food and Drug Administration's '' Bad Bug Book''
{{Authority control
Conosa
Amoebozoa species
Parasitic amoebozoa
Taxa named by Fritz Schaudinn
Protists described in 1903