Enterohemorrhagic Escherichia coli is a pathogenic bacteria which are normally found in the gut of humans and warm blooded animals. These are transmitted by consumption of contaminated food, water, uncooked meat and other contaminated products. Most of the food outbreaks is associated with EHEC and some of them are even life threatening. Not all strains of the bacterium are harmful. But, serotype O157:H7 are of public importance as they are main cause of public outbreak of food born disease. They can cause bloody diarrhoea or haemorrhagic colitis i.e. they affect large intestine and then pass to the abdomen and cause abdominal cramps and bloody diarrhoea. Transmission is mainly through oral faecal. There can also be lot of asymptomatic carriers who shed bacteria in their faeces and infect others but do not show any sign and symptoms of disease on themselves (Marcon et al 2011).
Infection of EHEC is followed by the ingestion of the pathogen via contaminated food or water or other sources. It can colonize the gut and is very virulent, even a low dose can be sufficient to colonize the gut and cause life threatening disease. E.coli which produce shiga toxins also called Vero-toxins are one of the most emerging pathogens as they can cause severe disease to humans like Haemorrhagic Colitis and Haemolytic-Uremic syndrome (Rey et al 2005). Main types of toxin they produce are shiga toxins. There are two main type of shiga toxins shiga toxin1 and shiga toxin 2. These shiga toxins play important role in the pathogenesis of haemorrhagic and Haemolytic Uremic syndrome which can be fatal to immune compromised patients (Hwa &Stein 2009).
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In addition to toxin production these shiga toxin producing E.coli also produce a protein called intimin which helps the pathogen to attach to the intestinal epithelial cell and cause lesions in the mucosal wall. The primary reservoirs of these organisms are healthy domestic animals like cow, goat, sheep etc. Children and elderly are most vulnerable to these toxins (Rey et al 2005). The genetic information needed for the production of these toxins is genome of lambdoid prophages integrated in the chromosome. Study done on shiga toxins has revealed that shiga toxin 2 is more associated with human disease than shiga toxin 1(Olsson & Kaijser 2005).
Haemolytic uremic syndrome (HUS) is a disorder characterised by progressive renal failure which is associated with microangiopathic haemolytic anaemia. Haemolytic uremic syndrome infection is associated with shiga toxin or retro toxin which is produced by E.coli O157H7. This toxin binds to the epithelial cells in the intestine and invades the mucosal epithelial layer which results in bloody diarrhoea. Research on this infection shows a parallel relationship between infection and season change. E.coli O151:H7 is more predominant during summer and less common in winter and it could be to do with the activities of the people as people like to have BBQ during summer and they mostly enjoy outdoor activities and all which increases the rate of contamination (Norris 2005). A recent review done in USA has shown that the rate of development of HUS in patients with O157:H7 infection is 15 to 50% if they are treated with antibiotics. This bacteriophage carry toxin producing gene in the lysogenic phage and as the condition of the bacteriophage changes the temperate phage are released and they replicate in large quantities. They also found that some antibiotics treatments cause phage induction and there will be subsequent increase in toxin production level (Panos et al 2006)
Study done in Japan on animals using antibiotics fosfomycin and quinolones has suggested that use of these antibiotics can decrease mortality rate of mouse infected with E.coli O157:H7 while there was reduce count of STXs in faecal material as well (Panos et al 2006). Therapeutic use of fosfomycin kanamycin, ampicillin to the mice with low protein diet during the first 3 days of infection. When it was compared with non-treated ones the result showed low toxin production. In another experiment when the mouse was treated orally with fosfomycin or norfloxacin for 5 days the result showed that the survival rate was higher in infected and treated than those infected and non-treated ones.
Since then various study has been conducted in many parts of the world to access both the positive and negative effect of antibiotics. To make the result reliable most of the researchers have closely controlled variables like duration of sickness, serotype, and way of contamination and chances of developing HUS.
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Some researchers have argued that use of antibiotics to treat patients infected from E.coli O157:H7 is not a good option. Reasons they put forwarded to support their arguments are listed below: 1) Use of antibiotics eliminates our normal competing intestinal flora which leads to the overgrowth of E.coli O157:H7, especially if the strain is resistant to the antibiotic used they can also cause the release of SGLTs or they will induce the expression of STX gene of bacteriophage (Panos et al 2006). STX genes play a very important role in the pathogenesis of E.coli O157:H7 infection both intestinal as well as extra intestinal.
Other studies done on E.coli have suggested that the production of STX2 gene alone will be sufficient enough to cause HUS in humans. Those strains that was separated from the cases in Washington State between 1984 and 1987 showed that those strain was more likely to cause diarrhoea and progress to HUS to TTP if the genes present in the strain was only STX2 (Kim et al 2011).Experiment done in vitro using antibiotics polymyxin B, trimethoprim/sulphamethoxazole, ciprofloxacin have shown that it increases the rate of production of toxin highlighting the possibility that the use of antibiotics treatments can be detrimental. A continuously changing and sub lethal exposures of antibiotics to the bacteria demonstrate that bacteria can easily recover from those antibiotics and instead gain resistance against it (Kim et al 2011).
One of the prospective cohort studies conducted in UK and Ireland from 1997-2001 which involved 395 children who suffered from diarrhoea related to HUS was tested and they significantly found 329 had E.coli O157:H7 in their stool or serum. 67 children were treated with antibiotics like ciprofloxacin, metronidazole etc. The result showed a significant relationship between antibiotic use and kidney malfunction and some time as severe as death. EHEC infection treated with antibiotics show a very high chance of developing haemorrhagic colitis in children than those untreated (Panos et al 2006).
It is believed that STX1 and STX2 are associated with development of HUS following STEC infection. STX1 is structurally conserved and is similar to that produced by shigella dysentery type1. Both of them are composed of one active ââ‚¬Å“Aââ‚¬Â subunit and five bindingââ‚¬Â Bââ‚¬Â subunits. Till now no any effective treatment is available clinically however, passive antibody has shown some promising steps. Maurine monoclonal antibodies have shown some effect by neutralizing the activity of STX1 and STX2 in vivo and in vitro. Researches have used gnotobiotic piglet model which was infected with E.coli 0157:H7. This demonstrated that use of polyclonal porcine STX2 antiserum or STX2-specific human monoclonal antibodies can prevent the lesions associated with STX2 infection as well as neurological signs (Mukherjee et al 2002).
Shiga toxin producing E.coli are largely associated with food born outbreak in many parts of the world. They produce toxins which are very lethal to human, especially to children and elderly. In immune compromised people it can even cause death. From all the research done on antibiotics treatment on shiga toxins infection as well as EHEC we can see that use of antibiotics can be detrimental and can raise the infection further. Most of these experiments were conducted in vitro than in vivo. Research on antibodies use has shown some light on its treatment but as there is no lot of evidence it is harder to draw conclusion on that as well. It is difficult to conclude to support the use of antibiotics for the treatment without supporting experiments. It will be a good idea to conduct a large cohort study to see its effect and from there we can be able to draw some conclusion.