Shigatoxigenic ''Escherichia coli'' (STEC) and verotoxigenic ''E. coli'' (VTEC) are strains of the bacterium ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' that produce
Shiga toxin
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial or ...
(or verotoxin). Only a minority of the strains cause illness in humans.
The ones that do are collectively known as enterohemorrhagic ''E. coli'' (EHEC) and are major causes of
foodborne illness
Foodborne illness (also foodborne disease and food poisoning) is any illness resulting from the spoilage of contaminated food by pathogenic bacteria, viruses, or parasites that contaminate food,
as well as prions (the agents of mad cow disease ...
. When
infecting the
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before bein ...
of humans, they often cause
gastroenteritis,
enterocolitis
Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...
, and
bloody diarrhea
Dysentery (UK pronunciation: , US: ), historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications ...
(hence the name "enterohemorrhagic") and sometimes cause a severe
complication called
hemolytic-uremic syndrome (HUS).
Cattle
Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult ma ...
is an important
natural reservoir
In infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally lives and r ...
for EHEC because the colonised adult ruminants are
asymptomatic. This is because they lack vascular expression of the target receptor for Shiga toxins.
The group and its subgroups are known by
various names. They are distinguished from other strains of intestinal pathogenic ''E. coli'' including
enterotoxigenic ''E. coli'' (ETEC),
enteropathogenic ''E. coli'' (EPEC),
enteroinvasive ''E. coli'' (EIEC),
enteroaggregative ''E. coli'' (EAEC), and diffusely adherent ''E. coli'' (DAEC).
[ Two sentences were taken from this source verbatim.]
Background
The best known of these strains is
O157:H7, but non-O157 strains cause an estimated 36,000 illnesses, 1,000 hospitalizations and 30 deaths in the United States yearly.
Food safety specialists recognize "Big Six" strains: O26; O45; O103; O111;
O121; and O145.
[ A 2011 outbreak in Germany was caused by another STEC, O104:H4. This strain has both enteroaggregative and enterohemorrhagic properties. Both the O145 and O104 strains can cause hemolytic-uremic syndrome (HUS); the former strain shown to account for 2% to 51% of known HUS cases; an estimated 56% of such cases are caused by O145 and 14% by other EHEC strains.
EHECs that induce bloody diarrhea lead to HUS in 10% of cases. The clinical manifestations of postdiarrheal HUS include ]acute renal failure
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
, microangiopathic hemolytic anemia
Microangiopathic hemolytic anemia (MAHA) is a microangiopathic subgroup of hemolytic anemia (loss of red blood cells through destruction) caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes ...
, and thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
. The verocytotoxin (shiga-like toxin) can directly damage renal and endothelial cells. Thrombocytopenia occurs as platelets are consumed by clotting. Hemolytic anemia results from intravascular fibrin deposition, increased fragility of red blood cells, and fragmentation.
Antibiotics are of questionable value and have not shown to be of clear clinical benefit. Antibiotics that interfere with DNA synthesis, such as fluoroquinolones
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as we ...
, have been shown to induce the Stx-bearing bacteriophage and cause increased production of toxins. Attempts to block toxin production with antibacterials which target the ribosomal protein synthesis are conceptually more attractive. Plasma exchange offers a controversial but possibly helpful treatment. The use of antimotility agent
Antimotility agents are drugs used to alleviate the symptoms of diarrhea. These include loperamide (Imodium), diphenoxylate with atropine (Lomotil), and opiates such as paregoric, tincture of opium, codeine, and morphine. In diarrhea caused by ...
s (medications that suppress diarrhea by slowing bowel transit) in children under 10 years of age or in elderly patients should be avoided, as they increase the risk of HUS with EHEC infections.
The clinical presentation ranges from a mild and uncomplicated diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
to a hemorrhagic colitis
Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases.
In a medical context, the label ''colitis'' (without qualification ...
with severe abdominal pain. Serotype O157:H7 may trigger an infectious dose with 100 bacterial cells or fewer; other strain such as 104:H4 has also caused an outbreak in Germany 2011. Infections are most common in warmer months and in children under five years of age and are usually acquired from uncooked beef and unpasteurized
Pasteurization or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mild heat, usually to less than , to eliminate pathogens and extend shelf life.
Th ...
milk and juice. Initially a non-bloody diarrhea develops in patients after the bacterium attaches to the epithelium or the terminal ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
, cecum
The cecum or caecum is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix, to which it is joined). The wo ...
, and colon. The subsequent production of toxins mediates the bloody diarrhea. In children, a complication can be hemolytic uremic syndrome which then uses cytotoxins to attack the cells in the gut, so that bacteria can leak out into the blood and cause endothelial injury in locations such as the kidney by binding to globotriaosylceramide (Gb3).
Names
Names of the group and its subgroups include the following. There is some polysemy involved. Invariable synonymity is indicated by having the same color. Beyond that there is also some wider but variable synonymity. The first two (purple) in their narrowest sense
A sense is a biological system used by an organism for sensation, the process of gathering information about the world through the detection of stimuli. (For example, in the human body, the brain which is part of the central nervous system re ...
are generally treated as hypernyms of the others (red and blue), although in less precise usage
The usage of a language is the ways in which its written and spoken variations are routinely employed by its speakers; that is, it refers to "the collective habits of a language's native speakers", as opposed to idealized models of how a language ...
the red and blue have often been treated as synonyms of the purple. At least one reference holds "EHEC" to be mutually exclusive of "VTEC" and "STEC", but this does not match common usage, as many more publications lump all of the latter in with the former.
The current microbiology-based view on "Shiga-like toxin" (SLT) or "verotoxin" is that they should all be referred to as (versions of) Shiga toxin
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial or ...
, as the difference is negligible. Following this view, all "VTEC" (blue) should be called "STEC" (red). Historically, a different name was sometimes used because the toxins are not exactly the same as the one found in '' Shigella dysenteriae'', down to every last amino acid residue, although by this logic every "STEC" would be a "VTEC". The line can also be drawn to use "STEC" for ''Stx1''-producing strains and "VTEC" for ''Stx2''-producing strains, since ''Stx1'' is closer to the Shiga toxin. Practically, the choice of words and categories is not as important as the understanding of clinical relevance.
Infectivity and virulence
The infectivity
In epidemiology, infectivity is the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission — that is, how frequently it spreads among hosts that are not in a parent ...
or the virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
of an EHEC strain depends on several factors, including the presence of fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...
in the medium, the sensing of this sugar and the activation of EHEC pathogenicity island Pathogenicity islands (PAIs), as termed in 1990, are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. Pathogenicity islands are found in both animal and plant pathogens. Additionally, PAIs are found ...
.
Regulation of the pathogenicity island
EHEC becomes pathogenic through the expression of the locus of enterocyte effacement (LEE) encoded on its pathogenicity island. However, when EHEC is not in a host this expression is a waste of energy and resources, so it is only activated if some molecules are sensed in the environment.
When QseC or QseE bind with one of their interacting signalling molecule, they autophosphorylate and transfer its phosphate to the response regulator. QseC senses adrenaline
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands an ...
, noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, and an Endonuclease I-SceIII, encoded by a mobile group I intron within the mitochondrial COX1 gene (AI3); whereas QseE senses adrenaline, noradrenaline, SO4 and PO4. These signals are a clear indication to the bacteria that they are no longer free in the environment, but in the gut.
As a result, QseC phosphorylates QseB (which activates flagella), KpdE (which activates the LEE) and QseF. QseE phosphorylates QseF. The products QseBC and QseEF repress the expression of FusK and FusR. FusK and FusR are the two components of a system to repress the transcription of the LEE genes. FusK is a sensor kinase which is able to sense many sugars among which fucose. When fucose is present in the medium FusK phosphorylates FusR which represses LEE expression.
Thus when EHEC enters the gut there is a competition between the signals coming from QseC and QseF, and the signal coming from FusK. The first two would like to activate virulence, but Fusk stops it because the mucous layer, which is a source of fucose, isolates enterocytes from bacteria making the synthesis of the virulence factors useless. However, when fucose concentration decreases because bacterial cells find an unprotected area of the epithelium, then the expression of LEE genes will not be repressed by FusR, and KpdE will strongly activate them. In summary, the combined effect of the QseC/QseF and FusKR provide a fine-tuning system of LEE expression which saves energy and allow the mechanisms of virulence to be expressed only when the chances of success are higher.
Shiga toxins
Shiga toxins are a major virulence factor of EHEC. The toxins interact with intestinal epithelium and can cause systematic complications in humans like HUS and cerebral dysfunction if they enter the circulation. In EHEC, Shiga toxins are encoded lysogenic bacteriophages. The toxins bind to cell-surface glycolipid receptor Gb3, which causes the cell to take the toxin in via endocytosis. The Shiga toxins target ribosomal RNA
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosom ...
, which inhibits protein synthesis and causes apoptosis. The reason EHEC are symptomless in cattle is because the cattle do not have vascular expression of Gb3 unlike humans. Thus, the Shiga toxins cannot pass through the intestinal epithelium into circulation.
FusKR complex
This complex, formed by two components (FusK and FusR) has the function in EHEC to detect the presence of fucose in the environment and regulate the activation of LEE genes.
*FusK: is encoded by the z0462 gene. This gene is an histidine kinase
Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are hom ...
sensor. It detects fucose and then phosphorylates the Z0463 gene activating it.
*FusR: is encoded by the z0463 gene. This gene is a repressor of LEE genes. When z0462 gene detects fucose, phosphorylates and activates the Z0463 gene, which will repress the expression of 'le r', the regulator of the LEE genes. If z0463 gene is not active, the expression of the gene ler would not be repressed. The expression of 'ler' activates the remaining genes in the pathogenicity island inducing virulence.
*At the same time, the system FusKR inhibits the Z0461 gene, a fucose transporter.
Fucose increases the activation of the FusKR system, which inhibits the z0461 gene, which controls the metabolism of fucose. This is a mechanisms that is useful to avoid the competition for fucose with other strains of ''E. coli'' which are usually more efficient at using fucose as a carbon source. High concentrations of fucose in the medium also increases the repression of the LEE genes.
With low levels of fucose in the environment, the FusKR system is inactive, and this means that z0461 gene is transcribed, thus increasing the metabolism of fucose. Furthermore, a low concentration of fucose is an indication of unprotected epithelium, thus the repression of ler genes will disappear and the expression of the LEE genes will allow to attack the adjacent cells.
See also
* Fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...
* Gut flora
* Mucin
Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...
* Virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
Notes
References
Further reading
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External links
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Escherichia coli
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