Escherichia coli 0157:H7
Encounter and history
Escherichia coli are gram negative, rod shaped bacteria that are often used in laboratory studies and are usually harmless, residing in the human digestive tract as part of the normal flora. E. coli 0157:H7 is a pathogenic strain of E. coli that was first identified as a cause of disease in the United States in 1982, during an investigation into an outbreak of gastrointestinal illness. The organism is also called enterohemorrhagic E. coli (EHEC) because it causes abdominal pain with diarrhea that may contain blood. It lives in the intestines of healthy cattle and can contaminate meat during slaughter. It is believed that the widespread use of antibiotics by American farmers has promoted the horizontal gene transfer of antibiotic resistance genes and pathogenicity islands that has led to the creation of new pathogenic strains such as E. coli 0157:H7. The verotoxins that cause the disease are also called shiga toxins because they were acquired from Shigella strains. The illness predominantly occurs in the U.S., Canada, Japan and other industrialized nations of Europe. The average incidence in most countries ranges from 1-30 per 100,000 and the number of confirmed cases is increasing. In the U.S, about 73,000 people are infected anually, with an average of 61 deaths per year.
Entry, Spread and Multiplication
After food contaminated with E. coli 0157:H7 is ingested, it travels through the digestive system and attaches to the mucosal epithelial cells of the large intestine and forms a pedestal, which leads to destruction of the microvili. The bacteria will then multipy and produce toxins, which, in addition to diarrhea cause vomiting in 50% of cases and fever in 30%. The average incubation period is 3-4 days. The innoculum size is small(as little as 50 cells can cause illness) because E. coli 0157:H7 are acid tolerant and can easily pass through the stomach. The can also grow from 10-50C with an optimal temperature of 37C. Up to 10% of patients will develop hemolytic uremic syndrome, the most important complication from E. coli 0157:H7. This disease, charictarized by acute renal failure, almost exclusively affects children and the elderly and is fatal in as many as 5% of cases with intensive care. E.coli 0157:H7 is responsible for about 90% of HUS cases and is the leading cause of kidney failure in children. It is caused by the spread of the bacteria and the toxins throughout the bloodstream. Any organ may potentially be affected but certain renal cells are the most vulnerable.
Virulence Factors
The genome of E. coli 0157:H7 was recently sequenced and contains 1,387 new genes absent in non pathogenic strains. Analysis of the genome suggests that there are a variety of potential virulence genes that have yet to be explored, including fimbrial and other adhesions, secretion systems, and toxins. Many of the virulence genes are similar to those associated with pathogenesis in Salmonella and Shigella. Most of them are found on pathogenicity islands from viral DNA that is transmitted to the bacteria through the activity of a lysogenic phage. The two most important toxins, Stx1 and Stx2 (for shiga-toxin) are found on such islands and are composed of 5 B subunits surounding an active A component, which is transported into the cell after the B subunits recognize and bind to a specific glycolipid receptor, Gb3. This receptor is found on renal endothelial cells, blood vessels, smooth muscle cells(such as those of the intestinal tract) and red blood cells. Verotoxins cause cell death by inhibiting intracellular protein synthesis. Red blood cells are damaged as they are exposed to the toxins by the altered vasculature resulting from the inflamatory response. E. coli 0157:H7 has LEE genes and exibits attaching and effacing behavior, which alters the integrity of the mucosal epithelium.The ability to cross the intestinal epithelium and damage endothelial cells allows the bacteria to enter the bloodstream and to infect kidney cells which have the Cb3 receptor and are particularly vulnerable to the Stx toxins. This causes HUS. Being a gram negative bacteria, E. coli0157:H7 also has the LPS endotoxin, which is probably responsible for the fever that some patients experience.
Transmission
Outbreaks of E. coli 0157:H7 are almost invariably traced to foods of bovine origin. Other foods that have been implicated in the spread of E. coli 0157:H7 include apple juice and cider, milk, cheese, yogurt, soy beans, lettuce, tomatoes, other fruits and vegetables, and basically anything grown on or near herds of cattle. Contaminated water sources such as lakes, ponds and reservoirs have also been linked to outbreaks. Person to person transmission is an important source of infection by children, especially at day care centers. This occurs indirectly by the fecal-oral route. Because cattle on farms typically live for about 2 years before being slaughtered, long term treatment of cattle would be nessesary to prevent transmission. This is very expensive.
Outcome and Prevention
Without complications, the illness is self limiting and most patients fully recover after about 10 days. Antibiotics are contraindicated because they have not been shown to be effective in altering the course of the illness, may aggravate kidney complications, and contribute to antibiotic resistance. Patients with HUS often require blood transfusions and kidney dialysis. Almost 40% of patients who survive HUS will have some form of long term damage to their kidneys, nervous system or other areas such as the heart, lungs, and pancreas. Bloody diarrhea almost always precedes HUS and an early diagnosis is essential for effective treatment. Good sanitation and hygene are essential to preventing E. coli infections. Also, meat should be thoroughly cooked at temperatures above 70C in order to kill the bacteria and fruits and vegetables should be washed before consumption. Proper slaughtering procedures should be followed at farms to prevent fecal contamination, although there is currently not enough data to recommend ways to prevent contamination of EHEC during the growth, slaughter, proccesing of beef. A vaccine for cattle is not practical because the bacteria do not cause illness in cattle and therefore do not stimulate their immune response. It is recommended that physicians have any patient with bloody diarrhea tested for EHEC. There are a variety of ways to detect it in the laboratory. It is possible to screen for EHEC by inoculating stool specimens onto MacConkey medium containing sorbitol instead of lactose. PCR tests for verotoxin are also available.
References
http://www.who.int/mediacentre/factsheets/fs125/en/index.html
http://www.cdc.gov/nczved/divisions/dfbmd/diseases/ecoli_o157h7/index.html
http://www.cps.ca/english/statements/ID/id95-03.htm
http://www.enceph.com/feature_archive/gastro/v25n4p205.html
http://microbes.historique.net/ecoli.html
http://www.i-sis.org.uk/ecoli.php