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Marler Blog Providing Commentary on Food Poisoning Outbreaks & Litigation

Where the Hell did Shiga Toxin E. coli come from? A Literature Review – Part 3

How humans could have turned an obscure E. coli strain into a dangerous emerging infectious disease?

The furor of “pink slime” politics and unrelenting reports of foodborne illnesses in 2012 adds new meaning to the conclusion of Part 1 and Part 2, a series started earlier this year.  On the surface, one might think E coli evolution is a purely scientific, apolitical topic.  Is it?  The review ends with a brief exploration of host, environmental, and social factors that may influence selective pressures favoring the evolution and emergence of highly virulent STECs. The findings are put in perspective with regard to making evidence-based policy decisions to prevent foodborne disease from these pathogens.

(Download all three parts as PDF)

Under Pressure: Selecting for Virulent E. coli

The theory (promoted by movies like Food, Inc.) of E. coli O157:H7 being “born” on a feedlot just 30 years ago was debunked (see Part 2 of this series).  As discussed previously, current estimates of the age of the O157 serotype range from hundreds to many thousands of years. However, the ability for E. coli strains to evolve rapidly through gene acquisition and mobile elements may influence short-term evolutionary events resulting in increased risk of contamination of the food supply and human foodborne disease. Host and environmental factors including medical and agricultural practices can directly and indirectly influence the selective pressure on E. coli O157:H7 to develop and maintain new characteristics including virulence factors such as toxins and antibiotic resistance.

Armstrong et al. (1996) outlined three broad hypotheses that may have led to the emergence and recognition of E. coli O157:H7 in beef products. Given new information including recognition of novel vehicles of transmission ranging from fresh produce to cookie dough, a modification of their hypotheses might be:

1)    Conditions for the spread of E. coli O157:H7 and other pathogenic STECs from animals to humans have always existed, but these organisms have only recently emerged in animal populations.

2)    E. coli O157 and other pathogenic STECs have always been widespread in animal populations, but slaughter and meat processing practices have changed in such a way as to promote contamination of meat with this organism, and dissemination from the farm environment to surrounding fresh produce or other food crops.

3)    E. coli O157:H7 and other pathogenic STECs has always been present in the food supply but consumer practices have changed such that contaminated undercooked meat, raw milk, raw produce and other raw foods now lead to human infection.

4)    A combination of one or more of the above.

The Price of Fast, Cheap Burgers

Major structural changes in the U.S. agriculture and food processing industries promoting mass production of ground beef occurred concomitantly with the emergence of E. coli O157:H7 as a cause of foodborne illness (1). Coincidence?  Not likely.

It is important to consider the dynamics surrounding the first recognized outbreaks in the context of the evolution of this organism. Specifically, what were the potential selective pressures that favored the emergence and persistence of E. coli O157:H7 as an important cause of human foodborne disease?

As described in Part 2 of this series, the first recognized E. coli O157:H7 outbreaks were linked in the early 1980’s to undercooked hamburgers served at McDonald’s chain restaurants in Oregon and Michigan (2).  A decade later, another E. coli O157:H7 outbreak linked to burgers served at a fast-food restaurant chain (Jack in the Box) shook the beef industry (3).  The 1993 Jack in the Box outbreak that sickened nearly 700 and killed 4 people was perhaps the most significant driving factor in public health reform of the meat industry since Upton Sinclair published his book, The Jungle, where he exposed filthy conditions in America’s slaughterhouses and corruption in the meatpacking industry in the early 20th century (4). Similarly, the Jack in the Box outbreak exposed for the first time the numerous vulnerabilities in late 20th-century industrial agriculture that contributed to the tragic event in 1993 as expressed eloquently by Benedict in his book, “Poisoned,” published in 2011 (5).

Today, a myriad of potential contributing factors related pre- and post-harvest production, transportation, and preparation of ground beef have been recognized. For example, it is well documented that high concentrations of cattle in crowded pens before slaughter increase the opportunity for transmission of STECs between animals and into the environment (1, 6). The subsequent sourcing and mixing of cattle from numerous farms and mass production of ground beef products provide many opportunities for cross-contamination. For example, the traceback conducted during the 1993 Jack in the Box outbreak revealed that meat used in the implicated lots of ground beef could have come from 443 individual cattle from six different states and three different countries (1).

It is not difficult to envision retrospectively how changes in industrial agriculture practices combined with faster line speeds in the 1980’s could have promoted transfer of E. coli O157 from the hide or gut of beef carcasses to the finished product. Additionally, The public’s enthusiasm for fast, cheap food and the restaurant chain industry’s desire to meet this demand even at the cost of food safety clearly gave E. coli O157:H7 a new niche and pathway into the human gut.

Small Farms Not Exempt

Ironically, the increased popularity of raw, unprocessed foods perceived as more healthy may also be a factor contributing to increased human exposure to E. coli O157 and other STECs in the 21st Century. Following the Jack in the Box outbreak, and a string of other outbreaks associated with industrial agriculture and fast food, the public became increasingly disillusioned with modern food systems.  Fears over antibiotics, chemicals, and genetically engineered food further fueled the emergence of the so-called “foodist” movement.  Popular books and movies shunning modern agriculture brought a new hope to the health- and environmentally-conscious population by portraying small-scale, family farms and cows eating a “natural,” grain-free diet on pasture as a panacea for the problem with E. coli O157:H7. Although changes in U.S. industrial agricultural obviously played an important role in the pathogen’s short-term evolution and emergence as a human disease threat (see above), simple solutions such as “grass only” feeding have not panned out, as illustrated by continued E. coli O157:H7 outbreaks on both small and large farms. For example, the popularity of raw milk and cheeses made from raw milk correlates with an increase in E. coli O157 illnesses from dairy products. Similar to outbreaks linked to industrial foods, children have been the most severely affected by contaminated raw dairy products.

Super Bug or Super Cow

Since the early ground beef-related outbreaks in the 1980’s, there have been a number of important new discoveries in the transmission dynamics and ecology of E. coli O157:H7 among cattle. The interplay of animal host-pathogen relationships and the influence of genetics on both is an active area of research.  A hot topic in this field of research involves the phenomenon of “supershedders.” A supershedder is an animal that excretes a much higher concentration of E. coli O157 and has a higher rate of transmission to other animals (6). Supershedders expel more than 1 million E. coli O157 cells in every gram of feces (a gram is less than the weight of one penny). As a result, the environment where the cattle live can become heavily contaminated. It remains unknown if the driving selective factor in the occurrence of supershedders is the cattle host, the bacterial population, the environment, or a combination of both.

The Accidental Tourist

Humans do not appear to play any significant role in the natural history of E. coli O157:H7 or other STECs. The human gut is likely an “accidental host” of E. coli O157:H7 and has minimal influence on the evolution, ecology or long-term maintenance of this pathogen in nature. If humans are not the natural STEC host, it may explain in part why humans become severely ill, and even die from these infections, while cattle and other animal hosts carry the bacteria in their gut asymptomatically.

One explanation for the difference in pathogenicity involves the presence/absence of host receptors for the shiga toxins (stx1, stx2) produced by bacteriophages carried by STEC strains (7).  In short, some research shows that cattle may lack shiga toxin receptors, thus do not succumb to the damaging effects of these toxins.  In contrast, humans carry genes that express shiga toxin receptors and thus may suffer severe illness ranging from hemorrhagic colitis to HUS when exposed to these toxins during infection. Additional research is needed to further characterize these host-pathogen interactions and how they relate to clinical disease.

Virulence Factors – E. coli Super Powers or Evolutionary Baggage

If humans are indeed accidental hosts, what, if any, evolutionary benefit exists for E. coli O157 and other STECs (and their bacteriophages) in retaining virulence genes?

An intriguing theory was published by Steinberg and Levin (2007) suggesting that some of the virulence factors of E. coli O157:H7 provide protection against predation by grazing protozoa found in soil, water, and ruminant hosts such as cattle (8). Grazing protozoa are single cell parasites that “feed” on E. coli O157 bacterial populations. The authors hypothesize that the stx-encoding bacteriophage carried by E. coli O157:H7 may help it survive in food vacuoles after being consumed by protozoan parasites.

Another concern in medicine and agriculture that has a direct relationship to selective pressure on bacterial populations is the use/misuse of anitbiotics (9). There is evidence of antibiotic resistance among STEC strains from human and animal sources (10, 11). While antibiotics are generally contraindicated during E. coli O157:H7 infections due to increased risk of the patient developing HUS, antibiotic resistance may complicate therapeutic options in rare situations where treatment with antibiotics is needed.

The Elephant in the Room

It is worth making a final comment on factors that do not influence the evolution or ecology of E. coli O157:H7 and other pathogenic STECs. Despite the hype and sensationalism, there is no evidence or biological plausibility of genetically modified organisms (GMOs) being involved in the ecology or evolution of E. coli O157 or other pathogenic strains of E. coli. The non-pathogenic E. coli strain used in the cloning process to create genes that will be inserted into seeds to confer a specific genetic trait to future generations of plants (12). As such, laboratory E. coli is not present in the seed or the plant at the end of the process, and there is no opportunity for a person or animal that eats a transgenic plant being exposed to an E. coli lab strain.

Conclusions and Recommendations

The reality is that E. coli O157:H7 and other pathogenic STECs are entrenched in our food animal populations, especially ruminants. There is likely no turning the clock back on the evolution of these pathogens, which will continue to stay a step ahead of us through their evolutionary processes.  However, there are medical, agricultural, and social practices that may strongly influence the potential for these organisms to cause human foodborne disease. Thus, the hope in combatting these food safety threats lies in embracing scientific advancements that can inform evidence-based policy in best practices throughout the food chain.


  1.  Armstrong, G. L., J. Hollingsworth, and J. G. Morris. 1996. Emerging foodborne pathogens: Escherichia coli O157:H7 as a model of entry of a new pathogen into the food supply of the developed world. Epidem Rev 18:29-51.
  2. Riley, L. W., R. S. Remis, S. D. Helgerson, H. B. McGee, J. G. Wells, B. R. Davis, R. J. Hebert, E. S. Olcott, L. M. Johnson, N. T. Hargrett, P. A. Blake, and M. L. Cohen. 1983. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med 308:681-5.
  3. Bell, B. P., M. Goldoft, P. M. Griffin, M. A. Davis, D. C. Gordon, P. I. Tarr, C. A. Bartleson, J. H. Lewis, T. J. Barrett, J. G. Wells, and et al. 1994. A multistate outbreak of Escherichia coli O157:H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. JAMA 272:1349-53.
  4. Sinclair U. 1906. The Jungle. Doubleday, Jabber & Company, pp. 475.
  5. Benedict J. 2011. Poisoned: The True Story of the Deadly E. Coli Outbreak That Changed the Way Americans Eat. Mariner Publishing, pp. 314.
  6. Arthur, T. M., D. M. Brichta-Harhay, J. M. Bosilevac, N. Kalchayanand, S. D. Shackelford, T. L. Wheeler, and M. Koohmaraie. 2010. Super shedding of Escherichia coli O157:H7 by cattle and the impact on beef carcass contamination. Meat Science 86 (2010) 32–7.
  7. Pruimboom-Brees, I. M., T. W. Morgan, M.R. Ackermann, E. D. Nystrom, J. E. Samuel, N. A. Cornick, and H. W. Moon. 2000. Cattle lack vascular receptors for Escherichia coli O157:H7 Shiga toxins. Proc Natl Acad Sci 12;97:10325-9.
  8. Steinberg, K. M., and B. R. Levin. 2007. Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin-encoding prophage. Proc Biol Sci 274:1921-9
  9. Denamur, E. 2011. The 2011 Shiga toxin-producing Escherichia coli O104:H4 German outbreak: a lesson in genomic plasticity. Clin Microbiol Infect 17:1124-5.
  10. Meng, J., S. Zhao, M. P. Doyle, and S. W. Joseph. 1998. Antibiotic resistance of Escherichia coli O157:H7 and O157:NM isolated from animals, food, and humans. . J Food Prot 1998 Nov;61(11):1511-4.
  11. Schroeder, C. M., C. Zhao, C. DebRoy, J. Torcolini, S. Zhao, D. G. White, D. D. Wagner, P. F. McDermott, R. D. Walker, and J. Meng. 2002. Antimicrobial Resistance of Escherichia coli O157 Isolated from Humans, Cattle, Swine, and Food. Appl Environ Microbiol 68: 576–81.
  12. Boyle, R. How to genetically modify a seed, step by step. 2011. Available from: http://www.popsci.com/science/article/2011-01/life-cycle-genetically-modified-seed