04.07>> E. coli    
When Good Bacteria Turn Bad  

The year: 1982. The place: fast food restaurants in Michigan and Oregon. The crime: sickening many and leaving 18 people dead. The culprit: bacteria. Since 1983 outbreaks of Escherichia coli (or E. coli for short) infections have occurred sporadically throughout the United States. The one in 1982 was just the first. In 2006 and 2007, for example, dangerous E. coli outbreaks have been traced back to spinach and peanut butter. In between there have been dozens of reports of illnesses and even deaths caused by E. coli infections. Is this the result of an increase in the actual number of infections? A new, more dangerous kind of E. coli? Or just better reporting of what had been going on for years? What is all the noise about?

Escherichia coli, a kind of bacteria, are found in the intestinal tract of all mammals including humans. They live in the lumen of the intestines and some even aid in digestion. Normal E. coli are a necessary component in digestion. But there is something different about the particular E. coli strain that we are interested in this month. It is a rare, dangerous strain of E. coli that doctors and researchers have named O157:H7 (or sometimes just O157). There are two main virulence factors that make this particular strain of E. coli truly dangerous, pathogenic.

The first factor is the ability of E. coli O157:H7 to bind to the lining of the large intestine without getting washed away. Other forms of non-pathogenic E. coli found normally in the gut get washed away by the material flowing through the intestines. But E. coli O157:H7 have a surface protein called intimin that allow them to attach more closely to the lining of the gut. The second factor that makes E. coli O157:H7 so dangerous is its ability to produce poisonous substances or toxins.

The first sign of an E. coli O157 infection is bloody diarrhea. The bacteria cause damage to the lining of the large intestine and the toxins act on blood vessels in the gut, causing blood in watery stool or diarrhea. Once the lining has been broken down, the secreted toxins are more readily able to move through the intestinal lining and into the blood stream. These toxins are called shiga toxins (Stx). There are two types of shiga toxins: Stx1 and Stx2. Stx2 is more dangerous because, if taken up by the blood stream, it can cause kidney damage and eventual death in affected children or the elderly. The severe disease that these toxins induce is known as hemolytic uremic syndrome (HUS).
Stx-producing STEC attached to the villi of the terminal ileum

Dr. Saul Tzipori of the Tufts University Cummings School of Veterinary Medicine has been studying diarrheic diseases for over 30 years. Recently his team has developed a treatment to protect patients against HUS.

Dr. Tzipori and his team of researchers developed an antibody that intercepts and binds to the toxin molecules in the blood stream when it is given after the onset of diarrhea, but before the onset of kidney failure. As a result, Stx2 is not taken up by the cells in the kidney and other organs, preventing the development of HUS. This antibody was derived in genetically modified mice that are capable of making human antibody; it is extremely safe.

Dr. Tzipori’s novel idea is that this antibody targets the toxins, not the bacteria itself. This means that the antibody should work, even if the bacteria mutate. Therefore, the bacteria cannot develop resistance against this treatment. The novel antibody is now being developed into a drug.

Dr. Tzipori tested the drug in piglets and mice. The piglet is an ideal model since it develops both phases of the diseases: first diarrhea, which is followed by the effect of the absorbed toxin through the damaged gut.

The drug will soon be tested in human adult volunteers for safety and dose determination, known as Phase One clinical trials. After testing in healthy adult volunteers it will then be tested in additional (Phase Two and Phase Three) clinical trials in sick children.

Where are you likely to meet E. coli?

It used to be that the most common way of acquiring the bacteria was through undercooked meat. Cattle themselves are the major host to this type of E. coli bacteria, even though cattle show no signs of infection or contamination. This makes the bacteria very hard to detect in them. The outbreaks in 1982 were caused by undercooked meat at two McDonald’s restaurants. “Since that time, fast food chains have found that by cooking the meat more thoroughly under higher temperature, they have eliminated this problem,” said Dr. Tzipori. One way to avoid an unpleasant E. coli infection episode is to cook your meat until it is well done. While this conflicts with the way many people like their food, it is one sure method for overcoming E. coli. Freezing does not kill E. coli bacteria of this strain; thorough cooking appears to be the sole solution right now.

More recently, E. coli has been spread through water contamination. “Cows produce lots of fecal material,” said Dr. Tzipori, “which can make its way into the rivers and streams. Likely the cause of contamination of the spinach was irrigation using contaminated water.” And for those of you who like to have something to worry about, you can also be exposed to E. coli from unpasteurized milk (or juice), raw sprouts and salami. If you swim in infected pools or lakes or handle host animals and animal products, you can also be infected. Deer and swine can carry the bacteria as well.

The Microbiology and Botulism Research Unit.

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April 2007
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What A Year! is a project of the Massachusetts Society for Medical Research.

And it is funded by a grant from The William Townsend Porter Foundation

  Dr. Tzipori is a Professor of Microbiology and Infectious Diseases and Director of Infectious Disease at Tufts Cummings School of Veterinary Medicine. Dr. Tzipori received his DVM and PhD from the University of Queensland in Queensland, Australia. His dream was to become a cow doctor, although things didn’t quite happen that way. Bacterial diseases caused by E. coli are common amongst animals, so Dr. Tzipori initially began studying the disease in animals. He crossed over to human medicine once medical doctors were convinced that E. coli diseases occurred in humans, too. “The move was quite natural, actually,” said Dr. Tzipori. “As to my credentials as a veterinarian working to solve diseases of human health, 75 percent of infectious diseases that have appeared in the last 50 years are zoonotic diseases.”

To Learn More:

  • Tzipori, Saul, Abhineet Sheoran, Donna Akiyoshi, Arthur Donohue-Rolfe, and Howard Trachtman. "Antibody therapy in the management of shiga toxin-induced hemolytic uremic syndrome." Clinical Microbiology Reviews. 17(2004): 926-941.
  • Mukherjee , Jean, Kerry Chios, Dianne Fishwild, Deborah Hudson, Susan O’Donnell, Stephen Rich, Arthur Donohue-Rolfe, and Saul Tzipori. "Human stx2-specific monoclonal antibodies prevent systemic complications of Escherichia coli o157:H7 infection." Infection and Immunity 70(2002): 612-619.
  • Muckerjee, Jean, Kerry Chios, Dianne Fishwild, Deborah Hudson, Susan O’Donnell, Stephen Rich, Arthur Donohue-Rolfe, and Saul Tzipori. "Production and characterization of protective human antibodies against shiga toxin 1." Infection and Immunity 70(2002): 5896-5899.

About E.Coli and the Intestinal Tract:

  • On NPR, Deborah Franklin reports on the many little things living in your gut and the risk of unbalancing them with improper use of antibiotics. Click here and then read the story or click the “Listen” icon.

Written by Rebecca Kranz with Andrea R. Gwosdow, PhD

Gwosdow Associates



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