Tuesday, October 11, 2011

Escherichia coli


This is big. Such is the complexity of Escherichia coli, that it is both a necessary component of our natural microbiome and the single biggest producer of diarrhea among humans the world over. There is not one E. coli, but many. There is not one disease produced by it, but many. There is not one epidemiology by which it transmits, but many. "My name is legion, for I am many."

The Organism. Escherichia coli is comprised of both non-pathogenic strains as well as pathogenic strains. More generally, E.coli is a gram negative bacillus that is an important and normal component of the gut flora of mammals and birds. Below is an electron micrograph of a non-pathogenic E. coli strain:


These mutualistic inhabitants of the gut account for about 1 bacterium per thousand of the gut microbiome. The picture below is a computer generated image depicting a greater level of detail for those E. coli strains that contain flagella and pili.


The organism has multiple flagella used for motility, and is covered in pili, which are important for both adherence to the host cell and transfer of genetic material between organisms by way of plasmids.

What distinguishes between pathogenic strains of E. coli and the non-pathogenic strains that are comfortable residents of our gut? Virulence factors.

Before considering these virulence factors in detail, let's consider some background. The DNA of E. coli, and the enteric bacteria in general, is fantastically promiscuous. The genome undergoes a great deal of exchange and transfer with other members of the species, and even, potentially, with members of other bacterial species. It does this by extensive inter-bacterial gene exchange mechanisms, including conjugation and specialized transduction.


Conjugation is often referred to as "bacterial sex", though this is not accurate. The process of conjugation involves direct contact between bacterial cells via a specialized pilus. This pilus forms a bridge between the cells and allows for the transfer of plasmids, which are small circular units of extra-chromosomal, double-stranded DNA.

Conjugation

Transduction is the transfer of DNA between bacterial cells by an infecting virus, i.e. a bacteriophage. The phage is capable of carrying bacterial genetic material from one cell to the next:


These phages can be either virulent or temperate, which cause lytic and lysogenic infections, respectively. The latter form of bacterial infection is the most relevant to virulence factor DNA exchange among E. coli cells because infections with temperate phage results in the integration of the viral genome with the bacterial genome. During lysogenic infection, the integrated viral genome undergoes transcription and translation when the phage (now referred to as prophage) becomes active and, due to random errors during the process of viral genome replication, as new virions are produced their genomes may contain neighboring sequences of bacterial DNA that were accidentally transcribed with the integrated viral DNA. If these sequences correspond to genes that code for bacterial proteins then this genetic functionality can be transferred to new bacterial cells during subsequent bacterial infections with the phage. When bacteria acquire new genes by this process of specialized transduction, they are said to have undergone lysogenic conversion.

So, back to the virulence factors that endow certain E. coli strains with their pathogenicity.We will take a look at the major pathogenic strains to examine the specific virulence factors each exhibits.

Enterotoxigenic E. coli (ETEC): This strain adheres to small intestine enterocytes using its fimbriae. It produces heat labile (LT) and heat stable (ST) toxins, which increase host cell cyclic AMP and cyclic GMP, respectively. As a result, chloride secretion is enhanced and sodium chloride adsorption is inhibited and so there is a net secretion of water into the lumen of the gut. The LT toxin produced by ETEC is closely related to the cholera toxin produced by Vibrio cholerae.

Enteropathogenic E. coli (EPEC): This strain contains virulence factors that employ a more intimate strategy, which requires the bacteria to adhere to the host cells. In fact, the adhesin molecule required to bind the E. coli to the enterocyte is called intimin. The E. coli cell adheres to and alters the structure of the host cell in a rather remarkable way. EPEC secretes proteins into the host enterocyte. These proteins are receptors that embed in the host cell membrane and allow the organism to bind to the host cell. Subsequently, EPEC is able to manipulate actin in the enterocyte and create complexes that change the structure of the host cell. This adherence leads to important changes in host cell signal transduction, which in turn leads to the intestinal attachment and effacement lesions for which EPEC is known. The lesions lead to the secretion of water into the gut, as do the triggering of inflammation and tight junction permeability. Here is a nice animated video by YellowTree illustrating the general process:



Shiga toxin producing E. coli (STEC): This strain was formerly known, and is often still referred to, as enterohemorrhagic E. coli (EHEC). The adherence of STEC to enterocytes is quite similar to EPEC and is also accompanied by attachment and effacement lesions. However, there is a major difference between STEC and EPEC: the production of Shiga-toxins (STx), so named because of their close relationship with the toxin produced by Shigella dysenteriae. Shiga-toxins bind to enterocytes, enter the cell, and destroy the machinery of protein synthesis by cleaving an adenine residue from the 28s rRNA component of ribosomes. While this process leads to cell death, the Shiga-toxins can also go beyond the epithelium of the intestine leaving enterocytes intact. However, having breached the epithelium, the toxins still stimulate inflammation and gain access to the circulation. Since some endothelial cells also contain Shiga-toxin receptors, the endothelium associated with certain organ systems is subsequently targeted: namely the gut, the kidneys and the central nervous system. Vascular damage in these organ systems ensues.  E. coli O157:H7 is an STEC and has been responsible for several severe foodborne outbreaks in the US. This animated video below from Biovisual demonstrates the pathogenesis. Notice that the adherence process is very similar to what we saw for EPEC, but here presented with even more detail:



Enteroinvasive E. coli (EIEC): EIEC employ virulence factors known as invasins that allow the organisms to penetrate the enterocytes of the intestine. Once the EIEC organisms gain access to the host cell, they replicate inside and subsequently invaded neighboring host cells potentially leading to tissue damage. The pathogenesis is very similar to shigellosis.

Enteroaggregative E. coli (EAEC): They key virulence factor with EAEC is their capacity to aggregate on the surface of the intestinal epithelium forming a bacterial scaffolding, or biofilm. EAEC use specialized adherence fimbriae to build this aggregateive structure. E. coli O104:H4 is an EAEC and was responsible the severe European outbreak of 2011 that resulted in over 4000 cases and at least 50 deaths.

These pathogenic pathways are all nicely depicted in this summary graph published by Nature Reviews Microbiology:


Pathogenic E. coli are typically classified according to serotypes based on the O and H antigens (K and F antigens are also used to designate serotypes, but are not typically part of the naming convention). The O antigen is part of the lipopolysaccharide in the outer membrane of this gram negative bacterium. The H antigen is the flagellum. There are 181 known groups for the O antigen and 56 known groups for the H antigen.

The Disease. Pathogenic strains of E. coli cause watery diarrhea, dysentery, and other more severe complications. We'll again consider the clinical manifestations according to specific strains.

ETEC: Watery diarrhea is the clinical manifestation of important to humans. While ETEC disease is typically self-limiting it can, nevertheless, lead to dehydration especially in young children in resource poor settings. It is also probably the single biggest contributor to diarrhea incidence and prevalence, with approximately 400 million episodes per day in children under 5 years of age.

EPEC: Watery diarrhea is again the most important clinical manifestation in humans. The lesions produced by EPEC are an important source of water and electrolyte loss, though they do not produce dysentery. In addition, EPEC can also be an important source of persistent diarrhea and/or prolonged diarrheal episodes, either of which can become an important source of nutrient deficiency and malnutrition in children.

STEC: Dysentery common presents with STEC infection. However, watery diarrhea is also common and so a  spectrum of diarrheal disease from watery diarrhea to frank dysentery should be expected. Of particular concern with STEC infection is the potential for the dangerous complication, hemolytic uremic syndrome (HUS). As mentioned above, the STx receptors in some endothelial cells make the associated tissues susceptible to the Shiga-toxins in cases where it translocates beyond the intestinal epithelium. As such these toxins can effect vascular damage, which can lead to thrombocytopenia, hemolytic uremia, and renal failure. This constellation defines HUS and can be fatal.

EIEC: EIEC infection is very similar in clinical presentation to shigellosis. Frank dysentery often presents, but watery diarrhea is more common. The extent of intestinal tissue damage determines where on the spectrum between watery and bloody diarrhea that this disease will fall.

EAEC: This strain was considered to produce only watery diarrhea when clinically apparent, although it was also recognized as another important source of persistent diarrhea in young children in resource poor settings and, thus, a potential contributor to malnutrition. However, the 2011 outbreak of EAEC with E. coli O104:H4 in Europe demonstrated additional, and particularly severe, clinical presentation. Because this particular serotype acquired genes to produce Shiga-toxin, this novel EAEC can present with much more severe disease, including HUS.

The Epidemiology and the Landscape. The typical mode of transmission for all pathogenic E. coli is the fecal-oral route, as you would likely expect. Direct person to person contact can often be responsible for spreading infection, but more often contamination of food or water accounts for the greatest source of infections in both the developing and developed worlds.


In resource poor settings, the availability of safe, clean water underlies the ubiquity of ETEC infections in early childhood. Lack of infrastructural sanitation ensures that ETEC, as well as other strains, are constantly reintroduced into the water supply, which maintains a continuous cycle of infection for susceptible individuals in the population (primarily infants and young children).

In resource rich settings, ETEC and EPEC are not present in the water supply and therefore do not cause endemic diarrheal disease as they do in poorer geographic areas. However, STEC are responsible for sporadic and epidemic cases of diarrheal disease. Rather than inadequate water supplies, it is often the processing apparatus of large scale agriculture and the commercial food industry that is responsible for large-scale food-borne outbreaks involving STEC in the developed world. Several such outbreaks involving the STEC serotype O157:H7 have resulted from the cross contamination of beef products during processing, leading to tainted ground beef. Since the E. coli live in the intestines of cattle, if strict regulatory procedures are not followed then the content of the animal gut can come into contact with the flesh used for meat during the butchering process. Subsequently, if the meat is ground, the bacteria will be mixed throughout the meat product rather than residing solely on the surface.


Aside from these large infrastructural infection sources in both the developing and the developed worlds, contamination of food by individual food preparers is also a common source of infection in both geographic regions. An individual who is experiencing a diarrheal episode, or even someone who is asymptomatically shedding pathogenic E. coli in their stool, can contaminate the food they prepare and thus potentially infect many people.

The infectivity of the organism differs across different strains. ETEC require a fairly large number of organisms to cause an infection: the infectious dose for ETEC ranges between hundreds of millions to over a billion organisms. You'll recall, this is similar to the high infectious dose required of Vibrio cholerae, whose clinical presentation of diarrhea is also similar to (though often more virulent than) that of ETEC. On the other hand, STEC probably require much fewer organisms to initiate an infection: the infectious dose for STEC is around 100 organisms. This is much closer to the infectivity of Shigella species, and, again, STEC diarrhea is similar in presentation to that associated with shigellosis.

There are approximately between 2.5 and 4 billion cases of diarrheal illness each year thoughout the world, with the vast majority of these in small children. The map below is a cartogram produced by Worldmapper, which depicts each political territory resized as a function of the quantity of the variable being mapped, i.e. the total number of diarrhea cases per 100,000 population in children under 5 years of age:


Of these cases, approximately 3.5 million die. Again, most deaths occur in young children (>80% are under 5 years old). Most of the infections that result in diarrheal disease are bacterio-genic, with between 70% to 80% caused by pathogenic E. coliETEC alone is responsible for approximately 400 million diarrhea episodes every day in children under the age of 5 years. Deaths among children constitute a major global burden of disease. However, even beyond this, there is a substantive burden of diarrheal disease as measured by the disability-adjusted life years (DALY). The WHO map below depicts the diarrhea-associated global distribution of  DALYs: 

Age-standardised disability-adjusted life year (DALY) rates from diarrheal diseases by country (per 100,000 inhabitants).
   no data
   less than 500
   500-1000
   1000-1500
   1500-2000
   2000-2500
   2500-3000
   3000-3500
   3500-4000
   4000-4500
   4500-5000
   5000-6000
   more than 6000



Control and PreventionControl and prevention of infection with pathogenic E. coli begins by following the usual guidelines: improving sanitation in resource poor areas and maintaining vigilance in personal hygiene. In most settings in the world where E. coli is a significant contributor to diarrheal illness, improved infrastructure that can maintain adequate water resources is a first priority in its prevention.








Secondarily, personal hygiene at the individual level, especially in the context of food preparation, can also be very important in preventing the spread of E. coli-related diarrhea: consistent hand washing, boiling water, and thoroughly cooking food are all important in stopping the chain of transmission. Most importantly, since ETEC is probably the biggest contributor to global diarrhea overall, the implementation of these strategies would go very far toward eliminating the severe diarrhea burden in young children in much of the world. 


In the developed world, a particular focus on the food industry is necessary to reduce outbreaks of potentially deadly STEC infections. Stricter regulations of food processing to reduce cross contamination of meat products would be an important fist step. 


In addition, at the individual level, thorough cooking of all meat products, and especially ground beef, is a must. 






These organisms will not survive cooking, so even in the midst of poor agricultural practice, STEC infections can be prevented by cooking meat and maintaining good hygiene practices in the kitchen to prevent cross contamination of foods.

51 comments:

  1. This is an interesting article but it had me wondering why the strains that cause really severe disease don't die out from the population? Wouldn't most people stay away and then the patient dies relatively fast, limiting its spread potential?

    Also these organisms seem quite versatile and rapidly changing, I was wondering if it was possible for one strain to collect all the sub-types on one plasmid and become a super bug, or is one type endemic to an area?

    I am quite concerned about the manufacturing industries' role in this, if we can't get it right what chance does a family with no running water have?

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    1. When you live in a region where the pathogen is endemic and you have no knowledge or limited knowledge on prevention, you are at the mercy of being affected by the disease. The manufacturing industries often are all sanitations rules and most often the fines imposed on them by the government is very insignificant.

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    2. In regions where these diseases run rampant, it is difficult to tell people to 'stay away' from infected people; especially if they are family members. In most developing countries, different generations of the same family live under one roof therefore to stay away from ones' own home just because a fellow family member is sick is unrealistic and culturally speaking not going to happen. Lack of knowledge about the spread of infection and prevention methods also helps keep the disease alive in most populations.
      You also pose an interesting question about creating a superbug. I think biologically speaking it would be impossible but I'm not too sure. I think superbugs are named as such because of its ability to resist most anitbiotics and/or treatment.

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  2. The industrial food process is of some concern when I read this article. Even with these FDA regulations set in place, specifically here in the US, what steps are taken to ensure that industrial food processing cleanliness and safety is maintained? Is there some type of penalty for companies that are repeat offenders?

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    1. I think part of the problem here is funding for the USDA. One of the main issues is lack of manpower. There have been a few reports, over the past few years, of company warehouses that hadn't been inspected in years. There simply aren't enough workers.

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  3. It surprises me that there are between 2.5 and 4 billion cases of diarrheal illness throughout the world every year. Approximately 3.5 million of these cases die, the majority being small children. That is not a small nor acceptable number in my opinion. Although safe drinking water has a lot to do with the spread of E. coli and other diarrheal disease-causing bacteria, there must be precautionary measures in place, especially to decrease childhood mortality rates worldwide. The numbers of cases and deaths really speak for themselves, and stress the importance of improving water systems and hygiene once again.

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  4. The variety of strains of E.Coli offers complexity to a disease that causes such a high burden of disease. The impact diarrheal disease has on the entire world is neglected by many, especially by the political leaders of the developing world. Water is a fundamental of life and clean water seems to be so scarce in many areas.
    The surveillance and monitoring mechanisms that we have here in America for E.coli and other food borne illnesses are so far advanced then the mechanisms in place elsewhere. When there is an outbreak here, it makes headline news, as it should, because of its importance and rarity, but elsewhere it just is accepted as something that normally happens.

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  5. I do not think I ever realized how many different strains of E. coli there were. This makes it so difficult to focus on one particular one to control on a consistent basis. It is interesting and upsetting to know that it is responsible for over 400 million cases of diarrhea under 5 years old in the world. It is also interesting that again the main control and prevention method is hand hygiene, clean water, and proper sanitation, a luxury many countries lack. Even in developed countries, the food industry is improperly handling the food and is causing cross-contamination leading to E. coli outbreaks. This is very concerning because as many regulations are put into place, this country in particular, proper hygiene and sanitation should not be a problem in these large companies. When are these regulations going to stick at home and abroad? How many more people have to become sick, in America alone, for the food industry to tighten their safety measures? How many times does water and sanitation have to be implemented in an infectious outbreak for there to be a serious change in many of these countries?

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  6. Many of these pathogens make me wonder how much of this could be prevented through education. Just to think about how many of these cases and deaths could be prevented just by using fire to boil water and cook food properly or by building an outhouse.
    I wonder if a 'herd immunity'-type effect could take place - where through proper sanitation, some people are not as easily susceptible to becoming infected, which would decrease the number of cases and in turn the number of sources, which would make it more difficult for those not taking proper precautions to become infected (?) ...That made sense in my head.

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  7. I did not know how prevalent E.coli infections are and how easy measures such as hand washing or boiling water can prevent the diseases secondary to this aggressive bacteria. After reading this article I realize the importance of pulic health and how much impact one can have in people's lives.

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  8. It is fascinating how the exchange of genetic information through conjugation, transduction has played such a significant role in the verstatility and variable pathogenesis of this bacteria. One may easily forget all the non pathogenic strains that are a healthy addition to human gut flora. The key to preventing outbreaks is truly hygiene and safe production of produce and meat although even taking safety precautions may not prevent outbreaks as cows shedding organisms and stool may always be roaming upstream from a spinach field.

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  9. I can see that it is very difficult to combat E.coli with so many different strains present. I wonder how each strain fares with antibiotics, and if EAEC's ability to form biofilm makes it especially difficult to get rid of.

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    1. In reply to the previous comment:
      Patients suffering from a strain of E. coli that produces Shiga toxin, which can be deadly, appear to respond to the antibiotic azithromycin (Zithromax), according to German researchers. After receiving azithromycin treatment, these patients no longer carried the bacteria. Moreover, there were no signs of hemolytic uremic syndrome among any of the patients who took the antibiotic, the researchers said.

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  10. The importance of considering disease burden aside from just a death rate is important for diarrheal occurrence. The discomfort is a huge factor when considering the effect of diarrheal diseases on populations, and disability adjusted life years are an important way to assess this burden. The world map displaying the DALY rates show that like many of the other diseases, Africa is the only country that experiences multiple areas of extremely high rates. It goes to show that improving sanitation and clean water conditions in Africa would concurrently tackle many infectious diseases.

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  11. Given the similarity between the virulence factors of Shigella and STEC, it is likely that there was some sort of DNA exchange between a pathogenic Shigella species and E. Coli species. It is a wonder given the billions of humans in the world and many many more billions of bacteria in the human gut that there hasn't risen a super-bacteria species with several virulence factors from other species.

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  12. It is very amazing to me how a bacteria that can cause so much disease and devastation in the world behaves quite well and is actually needed if kept in its natural home. We need E.Coli as much as it needs the human intestines. As part of the normal flora in the large intestines, E.Coli (in addition to other coliforms) helps in production of Vitamin K, Vitamin B12, thiamine, biotin, riboflavin, and the enzyme lactase. E.Coli makes up about 75% of the gut flora and also enjoys the warm, nutritious environment of the colon. As long as we maintain proper hand hygeine and boil our food adequately and have adequate sanitation infrastructure, there is a nice symbiotic existence of E. Coli and humans.

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  13. Bills have been introduced to congress to control what goes on in the meat industry and to give more power to the USDA to shut plants down who are repeat offenders. Surprisingly, they have not become law. But I wonder how much they would do even if they were passed. Everyone has their price.

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  14. To anika:
    The enforcement of rules and regulations is the main issue when it comes to companies keeping clean practices while producing their products.
    The lack of priority and funding that goes toward enforcement is continously fought against for other interests.
    The main diarrheal disease risk factor can probably poor political attention to basic human resources.

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  15. In response to Nicole's comment, it is interesting to see when health regulations and politics clash. This is one of the reasons that E.coli outbreaks sometimes occur repeatedly due to the same source. Politics is a touchy subject here because if all the plants closed down that were repeat offenders, that would mean a large number of lost jobs. Unfortunately, we sometimes allow certain things to happen in spite of a potential health issue arising. Is this tradeoff really worth it though?

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  16. In response to Chris:
    The outbreak of E. coli centered in Germany running from May to July of this year caused the FDA to issue a press release stating:

    "The FDA considers any disease-causing strain of E. coli in food to be illegal. The FDA has provided scientific guidance to the produce industry on ways to minimize the risk of E. coli, and these methods will reduce the risk of the strain of E. coli causing the European outbreak as well as the more common strains."

    While I am not aware of the "scientific guidance" the FDA has provided, there are new guidelines that will be implemented starting in 2012 as part of the FDA Safety Modernization Act increasing the safety of food monitoring. There are a set of rules being constructed requiring food processing facilities to implement controls to reduce contamination with bacteria that cause illness.

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  17. To Anika;
    As of October 31, there is an E. Coli outbreak in North Caroline. All 24 victims attended the state fair, which ran from October 13 through October 23. Apparently this was not the first time there was an outbreak in this region. An E. coli outbreak in 2005 was traced to a petting zoo at the fair. Well enough, the bacteria was found in the feces of animals such as cattle, sheep and goats. On questioning, it was found that the confirmed cases petted animals had food without washing their hands. This is a good example of how hard it is to keep this infection under control even tough many rules and regulations are put into effect.

    http://www.cnn.com/2011/10/31/health/north-carolina-e-coli/index.html

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  18. In response to Bobbin, most of the various strains of E. Coli do not require antibiotic treatment at all. E. Coli infecting the GI tract is transmitted feco-orally and most are self-limiting, and depending on the severity of the electrolyte imbalance and dehydration from the diarrhea, treatment involves replacement of fluids and electrolytes. Antibiotic treatment is reserved for very severe cases, and in some cases, such as that caused by STEC, antibiotic treatment can make it worse and increase the risk of the complication hemolytic uremic syndrome. Antibiotics are not used in bloody diarrhea. Travellers diarrhea, ETEC, may be treated with antibiotics such as azithromycin, ciprofloxacin or rifamixin to end symptoms more quickly.

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  19. Waqas - you bring up a good point, but there are limitations on bacterial uptake of DNA which can severely hinder a naturally occurring bacterial superspecies.
    The main purpose of conjugation is to transfer the ability to conjugate, in the form of the F plasmid. Usually all that is transferred is the F plasmid. Only F- bacteria can receive the sex pilus which allows the transfer of DNA. It then becomes and F+ organism which can only give over DNA.
    In certain case the bacterium can become HFR, high frequency of recombination. In these strains conjugation occurs through a mating bridge and occurs more frequently than conjugation through a sex pilus. HFR strains come about when the F plasmid gets inserted into the main bacterial chromosome. When these strains undergo conjugation they can transfer all genes including antibiotic resistance and pathogenic genes. With HFR strains the mating bridge is unstable and often breaks before the complete transfer of the geneome. Similarly with transduction and transformation, while it is possible that the organism can receive an entire gene it is uncommon, usually they receive a portion of a full gene.
    The best way for one bacterial species to pass genes to another is through conjugation which generally requires the resistant or pathogenic gene to be located on the F plasmid. In HFR strains the gene needs to be close to the F gene, the further away the gene is from the F gene the less likely it is to be transferred.

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  20. In response to Stella:

    You are right about the nice symbiotic relationship between humans and gut bacterial flora. However, most of the colonic flora are not E. Coli but rather from the Bacteroides species (principally members of the B. fragilis group), Prevotella species , Clostridium species , and Peptostreptococcus species . Some really amazing evidence that the gut flora need us as from as we need them is that most of the bacteria in the human colon cannot be cultivated outside the human colon.

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  21. In response to Jen, because of the changes the FDA has made, food processing plants have to come up with plans on how to minimize contamination for their products. Also, since the Germany outbreak, additional import controls have been put in place so the strain isn't transported here. Considering North Carolina has just recently faced an e.coli outbreak, it wouldn't be good if another strain was imported, and if an exchange of virulence factors became a risk.

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  22. To Nicole,
    I am not sure that education alone is the solution. It seems like common sense that you should boil water and I do not think they survived for centuries without knowing that fact. Which makes me think its not a matter of education but resources. Water is so ubiquitous in use that the sheer quantity you need to boil for a village would be staggering. To heat that much water you would need a lot of firewood, which may not be that plentiful or a lot fuel which you may not be able to afford. In the end send as many teachers as you like and you will achieve only modest results unless you are offering more then simply information.

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  23. To Stan,
    You are right. We shouldn't educate them we should let the infected people all just die off as you have suggested. We should try that with HIV too!
    What may seem like common sense to you is not so common in the developing world. Spend some time in any developing nation and you will learn that very quickly. I have done health education in Ghana and people there did not know the importance of hand washing. They thought that malaria was caused by a dirty house.

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  24. In response to Stella, it is interesting that E. coli has such a love/hate relationship our bodies. It is true that E. coli lives naturally in our bodies and helps to produce several vitamins in our bodies, however it's virulence makes many people forget about the beneficial properties that it has. Hand washing, stronger infrastructures, and boiling water are definitely ways to control this bacteria, however it is never that simple or the amount of infected cases will not be so high. There should be much more enforcement on this matter to stress the importance of these types of prevention. The infrastructure will also be a hard task to tackle, because it involves the government and other political powers. More public health techniques should involve educating on the benefits of E. coli, as well as the dangers and how to decrease our chances of becoming infected.

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  25. Dear Nicole,

    Did you even read my statement before responding? Seems you took a gigantic leap of assumption and somehow landed in Ghana. If you actually read my response I said education ALONE will not solve the problem. Sure, there are people who may not know about hygiene but once again I will stress the importance of resources. Clean water is not easy to find in most of the world, we are lucky we have a quarter of the fresh water and the technology to filter more but that is not true elsewhere. Tell them to use their meager water supply to wash their hands and they will say " and what shall I drink then"? The simple truth is education is not enough and if the choice is a chance of diarrhea or the certainty of a quick death due to dehydration which would you choose?

    Completely off topic but, again education alone will not solve the AIDS crisis. Sure there is plenty of ignorance in the countries most afflicted and many do not know sex is the means of transmission but if you stopped there it would not be enough. You think that knowledge will save them from new cases? Clearly no, since they are unlikely to stop having sex entirely and that is all your education can do to protect them. The solution would again require resources in the form of identification of the infected with lab testing, treatment with medication and distribution of condoms.

    So scream the truth from the highest rooftops till you are blue in the face and in the end you will have done less then a bottle of water or a twelve pack of Trojans.

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  26. Stan,

    And I never said that education ALONE would do anything. Give them some Trojans and if they don't know what to do with them all of these resources are wasted. Education can result in resources, believe it or not. If people know what they need to stay healthy they can pursue it.
    Example: The woman who sweeps her house everyday to prevent malaria. If she actually knew what caused malaria and how to prevent it she could stay indoors at night, where long sleeves, assist in source reduction. None of which require any resources.

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  27. To Nicole R and Stan G: Education and resources are clearly both needed to combat the transmission of pathogenic E. coli. I think Stan and Nicole both make valid points. Increased education of disease-control methods (mostly water boiling and hand-washing) could significantly reduce the spread of the disease. Also, better infrastructure and water sanitation systems would be worthy investments for developing countries and their international governmental and NGO partners.
    Another (somewhat speculative) argument: less consumption of meat and more widespread adoption of vegetarian diets would certainly go a long way to reducing the spread of this enteric infection and countless others. I suspect that nearly every case of E. coli has a recent, if not direct, connection to animal feces, most likely cattle feces. Drastically reducing the number of animals raised for food might drastically interrupt the E. coli transmission cycle.

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    1. Allison GrossmanJuly 19, 2013 at 3:37 PM

      Nathan, I thought that your comment about moving away from meat was a really interesting one. It seems that even though vegetables account for a large number of E. coli infections, the cattle are a very important part of the picture. With that said, how many agricultural communities grow only vegetables and do not raise animals? I'm thinking that even if people don't consume the meat, the animal feces will still be relevant (if not as ubiquitous) in our food sources.

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  28. First off, I think this breakdown of E. coli presents a great deal of information in a very concise, cogent form. It well showed how this gram negative bacteria is both friend and foe to the human race; an essential part to our gut flora, as well as a potentially very virulent pathogen which can attack in a variety of ways. If I were to give any particular criticism to this article, I would have enjoyed also reading about 1: how "good" E. coli plays a symbiotic relationship in our gut, 2: how acute illness with the virulent versions of the bug are treated medically.

    That said, I believe the strength of this article lies in showing how multifaceted E coli can be, but juxtaposing that fact with how hygiene and proper food preparation play such a huge role in prevention. I thought it fascinating how E. coli can act like the ultimate mimic; taking on properties and looking very much like other bugs (ie. cholera or shigella) via genetic modification (ie. incorporation of new DNA via bacteriophage). However, by showing how sanitation and proper food preparation can be the key to combating many E. coli related illnesses, it offers us a view of E. coli as a multifaceted bacteria whose pathogenicity can be within a strong degree of reasonable control.

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    1. I agree with you Marco. It would be interesting to continue the discussion of the microorganisms that play vital roles in the human microbiome. The posts could start with information about the normal location of these microorganisms and their beneficial effects in normal, healthy physiologic function. We could also explore the flipside of these symbiotic relationships, including E. coli and other microbes. These tiny helpers can easily become harmful if a) they are in the wrong location (e.g. gut flora in the oral cavity or being ingested), or b) if they lead to opportunistic infections in the immunocompromised/immunosuppressed person (e.g. Candida albicans infections). I think more posts about the organisms of the human microbiome would be a great addition to the site.

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    2. Alexandr PinkhasovJune 20, 2014 at 3:50 PM

      Marco I really like your review of this article. In my opinion E. coli does receive a "bad rep" and most people think that it only has a disease causing role. Many people don't actually know of its function within our own body's. This article is very well structured and I personally found it easy to read. I believe this is an important factor especially if our goal is to reach out to the general public. I do agree with you in regards to expanding more on the symbiotic role that E. coli has within our gut. Another thing that I thought was really nice that the article mentions how contamination of food, and transmission can occur in unsanitary conditions.

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  30. I was discussing E.Coli with a co-worker and he mentioned one of the biggest outbreaks in the country occurred in 1993 in the Western United States from undercooked beef from the restaurant chain, Jack in the Box. When I heard this, I decided to do some research into this outbreak and what I read was shocking! The source I used to read about the outbreak was the CDC’s MMWR weekly report from April 16, 1993 (http://www.cdc.gov/Mmwr/preview/mmwrhtml/00020219.htm). The outbreak was traced back to carcasses from 5 slaughter plants in the United States and Canada. There were more than 500 confirmed cases of E. Coli due to this outbreak. Sadly, the majority of victims were children, with the median age being 7.5 years old. Four children died due to this outbreak. It’s sad that most E.Coli deaths occur in young children, it makes me wonder why this is the case? Reading the report makes me think twice about eating fast food, and I would especially be cautious about feeding fast food to children. I also wonder if Jack in the Box was liable for this outbreak because as we know from this post, if the meat was cooked properly the contaminated organisms would not survive and these deaths could have been prevented.

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    1. I was also curious about the history of E. Coli outbreaks in the U.S. at chain restaurants, especially given the recent outbreak linked to Chipotle restaurants. According to the CDC (http://www.cdc.gov/ecoli/2015/o26-11-15/index.html), there have been 53 cases linked to this outbreak, including 20 hospitalizations. The media has given substantial attention to the Chipotle outbreak, and I have read about how the stock of the company and the volume of customers frequenting their establishments have plummeted. However, compared to the size and severity of the 1993 outbreak that Joanne brought up, I was wondering how Jack in the Box was able to weather this scandal.
      I did a little research, and it seems that they were able to turn this into an opportunity for setting better food safety standards for the industry and policymakers introduced laws and programs to address the prevention of foodborne illnesses.

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  31. Is the trend towards more outbreaks? I think that there are two forces in our global, and domestic economy that might make E. Coli are more frequent and harder to track problem in the U.S..

    The first is our free market. We import a tremendous amount of foodstuffs. Already, it is a major public health challenge to identify which domestic producer is the source of an E. Coli outbreak. Are we concerned that there might be an outbreak whose source is a Brazilian, Chilean, of Mexican producer (three countries from whom we import a great deal of produce)? What are the challenges to identifying the risk and combating it?

    The second, sadly, is our trend towards deregulation. The FDA has precipitously lost funding over time, especially for inspection of food and water. We sometimes already see the effects of this. Do we expect to see more?

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    1. E.Coli is difficult to get wiped out from the earth because most people do not take E.Coli infection seriously, are less educated or are indifferent to it. There is a possibility to get more outbreaks in the future. Personal hygiene is often neglected by many people including not only family members but people who handle different food. We know that E.Coli bacteria has its ability to survive on the hard surfaces for weeks and only a few of them are responsible for causing a mild to severe diarrhea. Thats why the health policy workers believe that there is no need to policing the hygiene of food service workers.

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  32. E coli remains one of the most ubiquitous bacteria, yesterday An E. coli scare has prompted Niagara Bottling water producing company to voluntary recall 14 brands of its water products.
    They claimed the recall is out of an abundance of caution. it said there have been no signs of its product being contaminated or reports of consumers falling sick.
    The company said the operator of a spring that supplies two of its plants in Pennsylvania failed to report evidence of E. coli at the source. The bottler said it halted production, disinfected bottling lines and issued a voluntary recall.
    In August of 2011 an elderly woman died and at least 9 other people were sickened after eating fresh strawberries from an Oregon farm contaminated with E. coli O157:H7 , there was no recall of strawberries from the farm in this case because they claimed that produce is no longer being sold.However they ignored the fact that the strawberries may have been frozen or made into uncooked jam!
    and in may 2014 there was an E. coli found in hummus and dip products , the riskiest part is that the infectious dose needed to cause severe disease is very small and during food parties population is even at higher risk!

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  33. Khalid, I also heard about the bottled water being recalled as a "precaution." It really causes a company to have a bad reputation after such recalls have to be made. I believe it takes a lot for a company to make such a decision. However, I do not believe enough media attention was placed on the recall. Some people I asked at work and school did not even hear about it. Unless you're an avid news watcher, you may have missed information about the recall. In regards to the Oregon farm case you mentioned, that strawberry farmer could have bounced back if they said up front from the start that there was an issue with their product. It puts lives at danger when companies care more about their money and product than consumers health.

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    1. Stacy and Khalid both make really good points. Sometimes I feel these "recall"'s just aren't enough as a prevention measure. A lot of people only drink bottled water so you're right Stacy it should have been more widely publicized. I do believe maybe in areas where those brands of water are sold there was a bigger push of awareness. I wonder what surveillance techniques or systems were used to assess if anyone was affected by the contamination prior to the recall. Do i hear a cohort study forming ? :-)

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  34. Food safety is a concern when there are allowable levels of e coli in meat products. The eating of under-cooked ground beef is not worth the risk. It is just reality that E. coli lives in the intestines of cattle, it is scary that a pathogenic bacteria like E. coli can get mixed into the ground beef during the butchering process. One severe complication associated with E. coli infection is hemolytic uremic syndrome (HUS). The infection produces toxic substances that destroy red blood cells, causing kidney injury. HUS can require intensive care, kidney dialysis, and transfusions. An important consideration when asking for your medium rare hamburger.

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    1. Given that E.coli contamination of food or water accounts are the greatest source of infections in both the developing and developed worlds, I do agree that it is a risk to order undercooked meat. However, as a person with a true passion for good food, I must say that it is worth the risk as long as I’m eating from a place that maintains good hygiene practices in the kitchen to prevent cross contamination of foods. In my opinion, when it comes to meats, there is nothing worse that a well-done piece of meat, especially when we are talking about good cut of meat (i.e. rib eye, porterhouse, filet mignon, etc.). As I had also explained in my Tapeworms post, what we should expect is that the restaurants that serve undercooked meat are well monitored by public health officials that enforce the importance of cleanliness and fresh products. A responsible and well-managed restaurant that serves meat not fully cooked, should know the products they sell. However, mass production is another story since even though a restaurant is clean and responsible, their meat distributor might have other problems. For example, as explained in the post, processing apparatus of large scale agriculture and the commercial food industry might be responsible for large-scale food-borne outbreaks involving Shiga toxin producing E. coli (STEC) in the developed world. Thus, sometimes it is just out of their hands, despite their best effort. In the end, it is up to us to decide what we eat and since I do love a medium cooked piece of meat, I try my best to research about the cleanliness, quality, and service of the restaurants I visit.

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  36. Despite all the technology and safety systems we have in the US, there's no underestimating the need for common sense and good sanitary techniques. This problem is not just about the infectious component but the public health implications of migrant workers who who handle fruits and veggies. These foods get tainted due to the poor infrastructure given to the workers and also to poor irrigation and equipment standards. We need to address these aspects as well as curtailing the infection itself.

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  37. I think I will be making a similar comment here as I did on my tapeworm comment. I will not stand for not being allowed to eat a medium rare burger. I think it is the responsibility of the farming and factory farm industry to maintain high quality measures in order to properly abate E. coli outbreaks. It is unbelievable to me that we have no choice but to place our lives in the hands of massive industries who do not care enough to have appropriate sanitary systems, but such is life.

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  38. Considering that these organisms will not survive cooking, I am discouraged by the fact that e. coli is still such a large producer of diarrhea and contributor to child mortality. There are differences between the various strains that complicate planning prevention strategies. While STEC is more infective and has more dangerous complications than ETEC, but ETEC represents a greater proportion of the global burden of diarrhea overall. STEC is the main focus of developed nations, resulting in a focus on food processing, and ETEC is much more common in developing nations due to unsanitary water and lack of infrastructural sanitation.
    I did a little research to see if these two strains in particular differ in their ability to be killed via cooking in order to better understand the feasibility of preventing these two infections through low-cost means. The WHO claims that cooking foods to 70 degrees Celsius or higher will destroy EHEC (http://www.who.int/mediacentre/factsheets/fs125/en/). To prevent STEC infections, the CDC states that meat should be cooked to at least 70 degrees as well (http://www.cdc.gov/ecoli/general/), and research shows that boiling or microwaving spinach for 2 minutes can destroy 99% of the organism (4 minutes for 100%) (http://articles.latimes.com/2010/sep/14/news/la-heb-spinach-20100914). However, because of the lack of certainty or exactness in the infectivity of these organisms, messaging to consumers is not clear. In addition, many different types of foods can be potentially infectious, including unpasteurized juices or milk, or even ingested lake water while swimming. So while industry-wide changes are more difficult to put in place, I think more emphasis should be put on individual responsibilities for proper food preparation, especially when feeding children.

    But on the other hand, even that may not be likely. One writer for Time Magazine wrote that, in response to an E. coli outbreak and consequent recommendations to cut meat more thoroughly, "To me, a world in which no one ever eats a pink, juicy hamburger is one that's hardly worth living in." (http://content.time.com/time/nation/article/0,8599,2076261,00.html). This illustrates that even with good public awareness, personal choice may always triumph in the end anyway.

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  39. It seems frightening that E. Coli seems to be constantly evolving into new strains. The recent E. Coli outbreak at Chipotle is the STEC O26:H11 strain, also has Shiga toxins. Though not usually fatal, I wonder if there will eventually be a strain that has a high mortality rate. It is also unfortunate that prevention of the spread of E. Coli appears to be particularly difficult as well, especially when dealing with foods that are served raw. I wonder if there would be anyway to treat the water that is used to wash food that can eliminate the E. Coli bacteria if present without cooking the food itself?

    http://www.fda.gov/Food/RecallsOutbreaksEmergencies/Outbreaks/ucm470410.htm

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  40. E Coli is a bacteria so close to us that we have a hard time ridding the harmful strains. however with proper education, the harmless Ecoli can be avoided with minimal expense. Basic hygiene can prevent the Ecoli. However this basic education is lacking in many part of the world. there are people especially in developing countries who do not realize the connection between hygiene and health. Washing hands with clean water can be a novelty to some.
    I have seen many kitchens in developing countries that either did not have a sink or the cook did not wash his or her hands after cleaning dirtful items. let alone wear gloves(whats that?!)

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