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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.
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. coli. ETEC 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:
Control and Prevention. Control 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.
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. coli. ETEC 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 Prevention. Control 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.