SCIENCE & TECHNOLOGY
Escherichia coli: Friend or Foe?
By Max Sherman
This year’s deadly outbreak of Escherichia coli
infection in Europe has been linked to contaminated bean and seed sprouts from an organic
farm in Germany. At the time of this article, there
were 42 deaths and approximately 3,900 individuals infected with the rare and super-toxic
0104:H4 strain of the bacteria. More than 780
people developed hemolytic uremic syndrome,
which can lead to kidney failure.1
This follows earlier cases of the same disease in Scotland, although with a different strain
(0157). The Scottish outbreak caused a number of
deaths in elderly patients. Hemolytic uremic syndrome associated with diarrhea generally affects
children and is the most common cause of acute
renal failure in Europe and North America.2
According to the Centers for Disease Control
and Prevention (CDC), E. coli has also been
associated with food poisoning in the US from
consuming contaminated bologna, cheese, hazelnuts, romaine lettuce, poultry, beef, pizza and
cookie dough.3 E. coli is also the most common
etiologic gram-negative organism responsible
for US hospital-acquired urinary tract infections.
Most of these cases are associated with urethral
catheterization.5
E. coli bacteria can come in many toxic
strains or serotypes, which reproduce at astronomical rates, and are the basis for their potential
danger. The organism can double its population
in less than two hours under the right conditions.
It has the potential to make people, especially
children and the elderly, very sick.
The explosive population rate is also one
of the reasons E. coli can be used for genetic
research. All E. coli strains share the same
underlying biology, but they range from being
harmless and beneficial to being extremely
dangerous pathogens.5 The well-known K-12
strain, for example, is harmless. Other strains are
a different story and books have been written
that describe their mechanisms of virulence.6,7
This article briefly discusses the organism, its
virulence, sources of infection and how it has
revolutionized the study of biotechnology.
The Discovery
E. coli was first described in 1885 by Theodor
Escherich, a German pediatrician, in a
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monograph on the relationship of intestinal bacteria to the physiology of digestion in the infant.
The organism was isolated from the diapers of
healthy babies and he called it “bacterium coli
commune.”8
At that time, E. coli was merely one of a
rapidly growing list of species of bacteria that
scientists were discovering. In 1919, the name
Escherichia coli was proposed in his honor, but it
was not officially recognized until 1958.9
The Organism
Escherichia coli is a typical member of the
Enterobacteriaceae family that have their principal habitat in the bowels of humans and animals.
It is a short, straight gram-negative bacillus
that is non-spore-forming, usually motile with
flagella distributed over the whole surface, and
occurring singly or in pairs in rapidly growing
liquid cultures. A capsule or microcapsule is
often present, and a few strains produce a profuse polysaccharide slime.10
E. coli can exist in an anaerobic environment,
and is capable of fermentative and respiratory
metabolism. Its optimum temperature is 37º C
and it grows readily on a wide range of simple
culture media and on simple synthetic media.
E. coli is a member of the normal commensal
bowel flora in humans, and colonization takes
place soon after birth.11
It has been suggested that it has a nutritional
significance by providing a source of vitamins. In
nature, it is found in soil, water or at any other
site it can reach from its primary habitat, usually
by fecal contamination.
E. coli is a fairly typical bacterium, about
1 micron wide and 2 microns long. Thus, a billion of them can be packed into a volume of a
few cubic centimeters. They can be frozen alive,
and in the frozen state, they can persist almost
indefinitely without any serious loss. At a very
low temperature, such as in space, many of them
would likely survive for well over 10,000 years.12
The characteristics of this organism make E. coli
an ideal laboratory research tool.
Virulence
E. coli can be divided into two major groups:
pathogenic and avirulent E.coli. The pathogenic
groups have evolved with the ability to cause
disease in several body systems. Until recently,
the food industry focused E. coli prevention
efforts on a single strain of the bacteria, known
as 0157:H7, which was responsible for scores of
outbreaks and recalls.
Public health experts and the CDC have
identified six rarer forms, often referred to as the
“Big Six.” They have increasingly been found to
be the cause of illness related to food.13 The six
strains of non-0157:H7 identified by the CDC as
responsible for the majority of the non-0157 illnesses and deaths are 026, 0111, 0103, 045, 0121
and 0140.
These strains, like 0157, have the ability to
manufacture Shiga-like verotoxins that attack red
blood cells, ultimately destroying the scaffolding
of blood vessels and essentially cutting off blood
flow to vital organs. The acronym STEC, or Shiga
toxin producing E. coli, is frequently used to
describe these strains. The life-threatening condition it produces is described as hemolytic uremic
syndrome. Unlike other pathogens, it only takes
a very small number of E. coli bacteria to cause
illness.14
Most infections caused by E. coli are initiated
by the colonization of the host gastrointestinal,
respiratory and urinary tracts. E. coli is particularly adept at colonizing these mucosal surfaces
because of its rapid multiplication and ability to
attach to cells that line the mucosa. A number of
factors appear to enhance the virulence of E. coli,
including the serotype, serum resistance, hemolysin and aerobactin production and fimbriae.
E. coli strains are differentiated on the basis
of lipopolysacchride O, flagellar H and polysaccharide K antigens. Determination of the O:K:H
serotype is a refined method for typing E. coli,
as there are more than 170 O, about 56 H, and
approximately 100 K-antigens. Together, they
constitute the O:H system, which has played an
important role in studies on epidemiology and
pathogenesis of E. coli infection.
Serum resistance for E. coli is the outcome
of the combined effects of the organism’s lipopolysaccharide, capsule and certain membrane
proteins. Aerobactin and α-hemolysin are
secreted by pathogenic E. coli. Both have the
ability to break down erythrocytes and extract
iron-containing compounds necessary for the
organism to multiply. Type-1 Fimbriae (thin,
hair-like projections) enhance the organism’s
adherence to intestinal mucosa or urinary tract
and play a vital role in initiating an infection.
There are other virulence factors to consider
as well, including different varieties of Shiga
toxin, intimin (a bacterial outer-membrane protein) or the arcanely described pathogenicity
islands (PAIs). Intimin is required for intimate
attachment to the host cell. The most common
site of human infections is the gastrointestinal
tract due to the ease of access of E. coli ingested
in food and drink.15
There are at least five major classes of
enterovirulent E. coli that cause disease in
humans.
• Enterotoxigenic E. coli (ETEC) produce a
heat-vulnerable enterotoxin, a heat stable
enterotoxin or both. They also possess
surface antigens that enable them to
attach to intestinal epithelial cells.
• Enteroinvasive E. coli (EIEC) invade and
multiply in epithelial cells of the colon,
causing a dysentery-like illness.
• Enterohemorrhagic E. Coli (EHEC) may
be the leading cause for epidemics of
severe infections. It has been estimated
that more than 70,000 human cases of
EHEC infections occur in the US each
year.16
• Virulence mechanisms of the two
remaining classes—enteropathic E. coli
(EPEC) and enteroaggregative E. coli
(EaggEC)—are less clear.17,18
The terms and acronyms used to describe E. coli
are confusing and complicated, and it is difficult to discern all of the causative features and
strains (serotypes) for bacteriologists who are not
current with the massive amount of published
literature. The recent outbreak in Germany is a
good example. It was caused by a unique and
unusual 0104:H4 strain that can be distinguished
from other 0104:H4 strains because it contains
a prophage (a molecule of DNA in the chromosome of the cell) encoding Shiga toxin 2 and a
distinct set of additional virulence and antibioticresistance factors.19
Sources of Infection
E. coli is widely disseminated throughout the
food chain. In the 1990s and into the early
21st century, the majority of food-borne E. coli
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outbreaks were caused by the consumption of
contaminated ground beef. Numerous outbreaks
and massive recalls of contaminated meat products continue to plague the meat industry and
the public.
Water intended for recreation and for human
consumption can also become contaminated by
causes as simple as a heavy rainstorm. Other
means of transmission include person-to-person
and animal-to-person contact. It is also possible
that E. coli can be disseminated through the inhalation of dust particles.20
Bioresearch
In the early 20th century, scientists began to study
harmless strains of E. coli to understand the nature
of life.21 Now, more is known about E. coli than
about any other organism in the biosphere, including humans. The genome for E. coli is one of the
most extensively mapped of any organism.22
Generations of researchers have probed the
existence of the organism, carefully studying
most of its more than 4,000 genes and discovering more and more about evolution. Through
this work, scientists can see an ancient history
we all share—a history that includes the complex features in cells, the common ancestor of all
living things, in a world before DNA. With the
knowledge gained from E. coli, genetic engineers
can transform corn, pigs and even fish.
E. coli has also been used to define the
molecular and cellular mechanisms underlying how microbes cause disease.23 Thousands of
experiments have been run to understand the
growth of E. coli, and several Nobel prizes have
been awarded because of them.24
There are at least five reasons for using
E. coli in gene cloning and other genetic research.
The first is its relatively small genome size,
about 4,400 genes. Second is the rapid growth
rate. Genetic experimental results can be determined in hours instead of days or years. Third,
the organism is relatively innocuous, if properly handled. Fourth, the E. coli genome has
been completely sequenced and thus its protein
expression mechanisms are well known. Fifth,
and perhaps most important, is that E. coli is
readily transformed with plasmids (DNA that
can replicate independent of the main chromosome) and other vectors and easily undergoes
transduction by taking up foreign DNA.25
The collective knowledge derived from all
of the research makes it relatively simple for a
scientist to create a mutant E. coli with missing
genes and then to learn from its behavior what
that gene is for. Bacterial geneticists now have
a good idea of what all but 600 genes represent.
From the hundreds or thousands of papers published on E. coli comes a portrait of a living thing
that is governed by rules that often apply to all
of life.26
Final Thoughts
Carl Zimmer, an award-winning science writer,
perhaps best describes the friend and foe dichotomy for E. coli:
“E. coli may seem like an odd choice as a
guide to life if the only place you’ve heard about
it is in the news reports of food poisoning. There
are certainly some deadly strains in its ranks.
But most E. coli are harmless. Billions of them
live peacefully in my intestines, billions more in
yours, and many others in just about every warm
blooded animal on Earth. All told, there are
around 100 billion billion on Earth. They live in
rivers and lakes, forests and backyards. And they
also live in thousands of laboratories, nurtured in
yeasty flasks and smeared across petri dishes.”27
References
1.
Kupferschmidt K. As E. coli outbreak recedes, new questions come to the fore. Science. 2011;333:27.
2.
Fitzpatrick M. Haemolytic uraemic syndrome and E coli
0157. BMJ. 1999;318:684-5.
Centers for Disease Control and Prevention. http://cdc.
3.
gove/print.do?url=http://www.cdc.gov/ecoli. Accessed
1 July 2011.
Sussman M (ed). Escherichia coli: Mechanisms of Virulence.
4.
Cambridge University Press, Cambridge UK, 1997.
Ibid.
5.
6.
Ibid.
7.
Benedict J. Poisoned: The True Story of the Deadly E. coli
Outbreak that Changed the Way Americans Eat. Inspire
Books, Bueva Vista, VA, 2011
Escherich T: Die Darmbakterien de Sauglings und
8.
Neugeborenen. Fortschritte der Medizin. 1885;3:515-22.
9.
Wikipedia. http://wikipedia.org/wiki/Theodor_
Escherich. Accessed 11 July 2011.
10. Op cit 4.
11. Sachs JS. Good Germs, Bad Germs. Hill and Wang
Publishers, New York, 2007.
12. Crick F. Life Itself: Its Origin and Nature. Simon and
Schuster, New York, 1981.
13. Neuman W. Food companies act to prevent consumers
from E. coli illness. New York Times. 15 July 2011.
14. National Consumers League. http://nclnet.org/
newsroom/press-releases/536-consumer-advocatesurge-usda-to-dec. Accessed 16 July 2011.
15. Op cit 4.
16. Yong Y et al. Crystal structure of EHEC intimin: insights
into the complementarity between EPEC and EHEC.
PLoS One. 2010;5(12)e15285.
17. Levine MM. Escherichia coli that cause diarrhea,
enterotoxigenic, enteropathogenic, enteroinvasive,
enterohemorrhagic and enteroadherent. J. Infect Dis. 1987;
155(1):377-89.
18. Scotland SM et al. Properties of strains of Escherichia coli
in relation to their enteropathic or enterohemorrhagic
classification. J. Infect Dis. 1990; 162(5):1069-74.
19. Rasko DA et al. Origins of the E. coli strain causing an
outbreak of hemolytic-uremic syndrome in Germany.
NEJM. 2011. DOI:10.1056/NEJMoa1106920.
20. E. Coli litigation. http://ecolilitigaton.com/ecoli_vehicles. Accessed 11 July 2011.
21. Zimmer C. Microcosm: E. coli and the New Science of Life.
Vintage Books, New York, 2008.
22. Op cit 4.
23. Vallance BA, Finley BB. Exploitation of host cells
by enteropathogenic Escherichia coli. PNAS. 2000;
97(16):8799-8806.
24. Op cit 4.
25. About.com. http://biotech.about.com/od/technicaltheory/tp/Ecoli.htm?p=1. Accessed 11 July 2011.
26. Op cit 21.
27. Ibid.
Author
Max Sherman is president of Sherman Consulting Services Inc.
He can be reached by email at [email protected].
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