| Shigatoxigenic and verotoxigenicE. coli | |
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| Specialty | Infectious disease |
ShigatoxigenicEscherichia coli (STEC) andverotoxigenicE. coli (VTEC) are strains of the bacteriumEscherichia coli that produceShiga toxin (or verotoxin).[a] Only a minority of the strains cause illness in humans.[2][failed verification] The ones that do are collectively known asenterohemorrhagicE. coli (EHEC) and are major causes offoodborne illness. Wheninfecting thelarge intestine of humans, they often causegastroenteritis,enterocolitis, andbloody diarrhea (hence the name "enterohemorrhagic") and sometimes cause a severecomplication calledhemolytic-uremic syndrome (HUS).[3][4]Cattle are an importantnatural reservoir for EHEC because the colonised adult ruminants areasymptomatic. This is because they lack vascular expression of the target receptor for Shiga toxins.[5] The group and its subgroups are known byvarious names. They are distinguished from other strains of intestinal pathogenicE. coli includingenterotoxigenicE. coli (ETEC),enteropathogenicE. coli (EPEC),enteroinvasiveE. coli (EIEC),enteroaggregativeE. coli (EAEC), and diffusely adherentE. coli (DAEC).[6]
Shiga toxin–producing Escherichia coli arezoonotic pathogens, in that they can be found in the gastrointestinal tract of cattle and sheep, and can infect humans. They are globally-occurring bacteria.[7]
The best known of these strains isO157:H7, but non-O157 strains cause an estimated 36,000[citation needed] illnesses, 1,000 hospitalizations and 30 deaths in the United States yearly.[8] Food safety specialists recognize "Big Six" strains: O26; O45; O103; O111;O121; and O145.[8] A2011 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.[citation needed]
The clinical presentation in humans ranges from a mild and uncomplicateddiarrhea to ahemorrhagic colitis 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 andunpasteurized milk and juice. Initially a non-bloody diarrhea develops in patients after the bacterium attaches to theepithelium of the terminalileum,cecum, andcolon. 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).[citation needed]EHECs that induce bloody diarrhea lead to HUS in 10% of cases. The clinical manifestations of postdiarrheal HUS includeacute renal failure,microangiopathic hemolytic anemia, andthrombocytopenia. The verocytotoxin (shiga-like toxin) can directly damage renal and endothelial cells. Thrombocytopenia occurs as platelets are consumed by clotting. Hemolytic anemia results from intravascularfibrin deposition, increased fragility of red blood cells, and fragmentation.[6]
Antibiotics are of questionable value and have not shown to be of clear clinical benefit. Antibiotics that interfere with DNA synthesis, such asfluoroquinolones, have been shown to induce the Stx-bearing bacteriophage and cause increased production of toxins.[9] 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 ofantimotility agents (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.[6]
Names of the group and its subgroups include the following.[10] There is somepolysemy involved. Invariablesynonymity is indicated by having the same color. Beyond that there is also some wider but variable synonymity. The first two (purple) in their narrowestsense are generally treated ashypernyms of the others (red and blue), although in less preciseusage 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",[3] 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, as the difference is negligible. Following this view, all "VTEC" (blue) should be called "STEC" (red).[1][11]: 2–3 Historically, a different name was sometimes used because the toxins are not exactly the same asthe one found inShigella 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" forStx1-producing strains and "VTEC" forStx2-producing strains, sinceStx1 is closer to the Shiga toxin. Practically, the choice of words and categories is not as important as the understanding of clinical relevance.
| Name | Short form |
|---|---|
| enterohemorrhagicE. coli | EHEC |
| hemolytic uremic syndrome–associated enterohemorrhagicE. coli | HUSEC |
| shiga toxin–producingE. coli | STEC |
| shigatoxigenicE. coli | STEC |
| shiga-like toxin–producingE. coli | SLTEC |
| verotoxin-producingE. coli | VTEC |
| verotoxigenicE. coli | VTEC |
| verocytotoxin-producingE. coli | VTEC |
| verocytotoxigenicE. coli | VTEC |
Theinfectivity or thevirulence of an EHEC strain depends on several factors, including the presence offucose in the medium, the sensing of this sugar and the activation of EHECpathogenicity island.[citation needed]
To successfully colonize the gut of its host, EHEC relies on attaching itself to epithelial cells in the large intestine. Atype III secretion system (T3SS) consisting of intimin and its translocated intimin receptor (Tir), is expressed on the cell membrane, allowing EHEC to intimately attach to host cells. T3SS secretesTir into the host cell membrane and induces the formation of pedestals, resulting in attachment and effacing lesions on epithelial cells. Expression of T3SS associated genes is regulated byLEE and is activated through the EvgSA two component system in the presence of nicotinamide.[12]
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.[13] In EHEC, Shiga toxins are encoded by lysogenic bacteriophages. The toxins bind to cell-surface glycolipid receptor Gb3, which causes the cell to take the toxin in viaendocytosis. The Shiga toxins targetribosomal RNA, which inhibits protein synthesis and causesapoptosis.[14] 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.[5]
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EHEC becomes pathogenic through the expression of thelocus 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.[citation needed]
When QseC or QseE bind with one of their interacting signalling molecule, they autophosphorylate and transfer its phosphate to the response regulator. QseC sensesadrenaline,noradrenaline, and an Endonuclease I-SceIII, encoded by a mobile group I intron within the mitochondrialCOX1 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.[citation needed]
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.[citation needed]
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.[citation needed]There are rare STEC without LEE, seeNewton, HJ; Sloan, J; Bulach, DM; Seemann, T; Allison, CC; Tauschek, M; Robins-Browne, RM; Paton, JC; Whittam, TS; Paton, AW; Hartland, EL (2009)."Shiga toxin-producing Escherichia coli strains negative for locus of enterocyte effacement".Emerg Infect Dis.15:372–80.doi:10.3201/eid1503.080631.PMC 2681110.PMID 19239748..
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