Escherichia coli (or E. coli for short) is no stranger to people these days. Every so often, E. coli crops up on the news, and more often than not the reports sombrely tell of the latest death toll attributed to this 'killer bug' in poorly-prepared food, or as the lead player in the latest meningitis scare. Most people have first-hand experience of the role E. coli plays in diarrhoea¹.

E. coli was first discovered in the human colon by a German scientist named Theodor Escherich in 1885. Escherich also showed that some strains of E. coli were responsible for diarrhoea and gastroenteritis². Although the bacteria were initially called Bacterium coli, the name was later changed to Escherichia coli in honour of its discoverer. Technically speaking, E. coli is a rod-shaped, Gram-negative, facultatively anaerobic bacterium in the family Enterobacteriaceae.

Over the years, as microbiology expanded as a field in science, people learned of the roles that microorganisms played in life - more often than not, as the cause of disease. However, E. coli isn't all monster. What most people don't know is that E. coli is not only a pathogen, it is an indispensable part of the global ecosystem, and it is vital to the maintenance of human health and is a crucial tool in the advancement of science and understanding.

E. coli: Foe

Even the most innocuous microorganism around is capable of causing different types of disease when circumstances permit. Staphylococcus aureus, a normal resident of the skin, causes toxic shock syndrome and skin infections, among other things. Streptococcus pyogenes, which you will find in anybody's throat, is the cause of sore throat, scarlet fever, and, in its most virulent form, the horrifying flesh-eating disease known as necrotizing fasciitis. And yet, these bacteria play second fiddle to E. coli where infections are concerned.

One would be amazed, or even horrified, to learn of the multitude of diseases that E. coli is capable of causing. There is probably no part of the human body that it is not capable of infecting, from gastrointestinal tract-related complications such as diarrhoea, dysentery and Haemolytic Uremic Syndrome (HUS) to urinary tract infections, pneumonia and even meningitis.

Haemolytic Uremic Syndrome

Haemolytic Uremic Syndrome (HUS) is E. coli's manifestation in its worst possible form. Caused by the infamous strain E. coli O157:H7, the bacteria is transmitted to humans in the form of undercooked beef, raw milk and apple cider, among other things. Once inside the human body, it colonizes and multiplies inside the gastrointestinal tract, producing a deadly toxin that kills the lining cells of the tract. If the bacteria is not stopped, it will continue to spread and wreak havoc, perforating the colon and causing it to haemorrhage and spread infection throughout the abdominal cavity. Eventually, blood transfusion and haemodialysis will be required to save the person's life.

Also, this bacteria readily infects the intestinal tracts of farm animals, causing their intestine lining to inflame. When farmers started giving their livestock antibiotics to ward off infection, this unknowingly selected a group of E. coli that had acquired a drug-resistance gene from the bacteria that causes dysentery, Shigella dysenteriae. This drug-resistance causes antibiotics therapy to fail. Even worse, the bacteria harbours a bacteria-infecting virus (known as 'bacteriophage') which carries the gene for a toxin also found in Shigella. Thus, when antibiotics therapy is carried out, the phage is induced to go into the cell-breaking (lytic) cycle, which causes multiple copies of this toxin gene to be produced, and subsequently for the amount of toxin produced to escalate. This, if you have been reading carefully, is exactly the opposite of what drug therapy is supposed to do.

Nosocomial Infections

Nosocomial infections are infections acquired in the hospital. The hospital is meant to be a place of rest for a patient, a sanctuary where they can seek comfort and healing from those who know best what to do with their condition. Unfortunately, because the hospital is also a place where sick people with infectious diseases go to, it is inevitably a reservoir for some of the nastiest bugs around.

According to hospital statistics, roughly 5% of hospitalized patients will contract infections during their stay; 10% of this occurs in the Intensive Care Unit. Approximately 50% of all patients who require catheterization for more than 5 days develop bladder infection. Abnormalities or obstruction of the urinary tract or faecal incontinence are also optimal conditions for infection. More often than not, it is the E. coli that is to blame.

Urinary tract infections are a very, very painful thing. The number one characteristic of a urinary tract infection is the abominably intense burning sensation while urinating. Other symptoms include the need to urinate frequently, and a feeling of fullness over the bladder, no matter how many times one has visited the lavatory. Happily, in many early cases of infection, removal of the catheter solves the problem because the bacteria would be forced to multiply in areas where stagnant urine collected, and would be flushed out by repeated calls of nature. However, if they are not removed they may cause a lot of trouble as many hospital-acquired strains of E. coli are drug-resistant.

Besides urinary tract infections, E. coli is also reportedly responsible for 10% of surgical wound infections, and 6% each of respiratory tract infections and septicaemia³ in the hospital environment.

Travellers' Diarrhoea

There is a reason why doctors warn you not to drink unboiled water in developing tropical countries - travellers' diarrhoea can be a nasty nuisance if you're going to be tromping around half the world.

Travellers' diarrhoea is caused by enterotoxigenic E. coli, which is so named because it produces toxins once it colonises the epithelial cells of the small intestine. These toxins are most likely 'borrowed' from another nasty diarrhoea-causing bacteria, Vibrio cholerae (which causes cholera and can be found in clams living in contaminated waters). These toxins cause massive quantities of water to be lost from the body through the anus, and in severe cases can cause dehydration and electrolyte imbalance, both of which can lead to death if the disease is not stopped in time with antibiotics

Interestingly, E. coli was the leading cause of diarrhoea among US troops during the 1991 Gulf War, more than half of whom suffered two or more episodes of the disease.

Meningitis

One of the diseases that rogue strains of E. coli are capable of causing is meningitis.

Brain infections are an especially serious matter, especially if it strikes the very young. The mortality rate for E. coli meningitis in infants is pretty dire: From forty to eighty percent. A large number of the survivors will be left with neurological or developmental abnormalities. Studies have indicated that pregnant mothers are more susceptible to colonisation by a strain of E. coli with a particular antigen⁴ known as K1, and the infection is subsequently spread from mother to child. It is still currently unknown how K1 predisposes infants to developing meningitis, but interestingly, a large portion of this antigen seems to be very closely related to that of another meningitis-causing bacteria, Neisseria meningitides.

It can only be called fortunate that the pregnant mothers themselves are not predisposed to catching meningitis from E. coli as this bacteria has rarely been identified as the cause for adult meningitis.

E. coli: Friend

The humble E. coli has always been the microbe of choice in research. This goes back to the 1950s when a group of scientists who were interested in studying basic biological processes decided that the best way to go about it was to use a common, simple, free-living microorganism, and base all their studies on that. Needless to say, they chose the E. coli. And from that day on, this rapidly-reproducing bacteria has been the model organism of almost everything from metabolic pathways to genetic regulation to DNA replication.

E. coli Are a Part of the Natural Gut Flora

There are far more bacterial cells inside a human than human cells⁵. A small number of the bacterial masses are our friend E. coli, and they're here to help. One of the main functions that the gut flora provides is that of protection. Without the help of E. coli our gut would be over-run by harmful bacteria and fungi. Our friendly and rapidly-replicating E. coli out-compete pathogens; they even inhibit the growth of pathogenic bacteria by secreting various substances that are toxic to non-indigenous bacteria. An interesting side-note: E. coli is responsible for the delightful way faeces⁶ smell!

The natural gut flora also secrete vitamins B12 and K as metabolic by-products. These vitamins are essential for our nutrition. Lactose-fermenting bacteria such as E. coli produce the enzyme lactase which breaks down lactose, a sugar found in milk and other dairy products. These microbes help confer lactose-tolerance⁷.

E. coli Are an Integral Part of the Ecosystem

Nitrogen is the most abundant gas in the atmosphere, constituting about 70% of the air that we breathe. In biological processes, nitrogen is an important element needed in the synthesis of proteins. Unfortunately, as Coleridge once lamented about water that was abundant and yet undrinkable⁸, this abundant store of nitrogen is inaccessible to most, being in gaseous form. Indeed the organisms on this earth would probably get little, if any, access to the nitrogen if not for the microbes in the soil that convert nitrogen gas into a form that is readily usable - ammonia.

However, just as microorganisms are needed to produce usable forms of nitrogen, they are also important in returning nitrogen to the environment. E. coli is one of the many hard-working little microbes that recycle nitrogen and return it to nature. Even though it can only carry out the first step of the process (dissimilative nitrate reduction) it nevertheless plays an important role in a world where one can afford to waste nothing. You may not think much of this role, but this process takes place largely in waterlogged areas where oxygen supply is minimal - a condition that the oxygen-loving E. coli clearly does not favour.

Sulphur is another important element for life and growth. Plants that are deprived of sulphur grow wilted and yellow. Many types of microorganisms depend on sulphur for growth, deriving energy from chemical reactions. And sulphur is found in a number of amino acids, which are the building blocks of protein. There is great need for microorganisms to do the job of recycling sulphur in the environment. And E. coli is deeply involved in this process. Its importance does not stop short of recycling; researchers are using isotope studies of various elements including sulphur to assess the extent of microbial activity in the environment, monitoring important links in the sulphur cycle and tracking microbial and higher organism food chain.

Genetic Engineering

Genetic engineering is the most recent tool of the ancient practice of biotechnology. It came about in the early 1970s, due to the simultaneous development of E. coli transformation and the discovery of enzymes in E. coli that are able to cut and rejoin DNA at will.

When a researcher 'transforms' a bacteria such as E. coli, they are permanently altering its genetic make-up. In the case of genetic manipulation, transformation refers to specifically the successful insertion of 'foreign' DNA (or more accurately 'exogenous' DNA) into the bacterium. In the early '70s E. coli was the best characterised bacteria, and the only known bacteria to possess plasmids. Plasmids are little circular rings of DNA and are independent of the bacteria's single chromosome, they can even replicate themselves on their own quite happily, which, for biologists, is a very useful thing indeed. With a very simple technique the plasmid of E. coli can be easily purified.

A class of enzymes were discovered in E. coli called 'restriction endonucleases', and it was found that they can cut DNA at specific base-pairs. When a specific restriction enzyme recognises a specific DNA base-pair sequence it cleaves it in a specific and predictable way. For example; EcoR1 recognises 'GTTAAC' (and its complementary strand) and cuts the DNA apart between the 'G' and the first 'A'. Sma1 recognises 'CCCGGG' and cleaves in between the third 'C' and the first 'G'. There are literally thousands of different enzymes one can choose from, and all cut in their own particular way.

Once the purified plasmid DNA is cut with your endonuclease of choice (physically done by incubating the enzyme and DNA in a buffer at 37°C for a while) it is possible, with the help of another enzyme called 'T4 DNA Ligase' to join (or 'ligate') them back together again. Or, more usefully, foreign DNA can be added together with the cut plasmid DNA and DNA ligase to create a chimaeric construct⁹ which can be used to transform other E. coli bacteria in culture. This is the heart of genetic engineering: Cutting plasmid DNA, inserting exogenous DNA, ligating, and transformation. From this point E. coli will replicate at an exponential rate, replicating, alongside its own DNA, your chimaeric plasmid in bulk. This is appropriately known as gene cloning.

In 1978 a company named Genentech was the first to exploit genetic engineering technology to make human insulin. Before Genentech medical insulin had to be extracted from pig pancreas, a costly and undesirable procedure. Genentech took the human gene responsible for insulin and inserted it into a plasmid and transformed our friend E. coli. The bacteria happily synthesised huge amounts of pure human insulin, making this compound that so many people depend upon for their lives affordable and accessible. Genentech went on to apply the same technology to clone and synthesis Human Growth Hormone, Activase (a product for dissolving blood clots in heart attack victims), Factor VIII (for haemophilia therapy) amongst others.

Today, genetic engineering is routine in even the most basic laboratories around the world. It is an extremely powerful tool and has revolutionised the pharmaceutical industry, enabling the development of numerous invaluable drugs.

Further Biological Studies Based Upon E. coli

Besides being a much-needed component of the ecosystem, E. coli also has a little bit of a celebrity status as a model for researchers. Here are some examples of studies that scientists have used E. coli as a model for:

• There are four ways by which chemicals can enter a cell. One of them is called group translocation, which is a process in which a given substance is chemically altered in the course of passage across the membrane. E. coli was the key to understanding the phosphotransferase system, the best studied case of group translocation involving transport of various sugars to which are added phosphate molecules while being moved.
• E. coli was an important model used in the study of electron transport chains, which is a process by which energy is produced in a cell.
• All the glamorous genome sequencing projects such as the Human Genome Project were done with E. coli as the primary workhorse. Huge plasmids called Bacterial Artificial Chromosomes (BACs) containing the DNA you want to sequence are made, cloned and purified all with the help of E. coli. Entire libraries of E. coli, which are comprised of hundreds of thousands of different colonies of E. coli clones, are made with enough variation in their BACs to cover the entire genomes of whatever organism you want. The BACs are purified, chopped up and sequenced automatically. The sequences fragments are pasted back together in a computer to assemble the genome.
• In pathogenecity studies, much attention has been devoted to a macromolecule on the surface of E. coli called the fimbrae, which plays a key role in the attachment of the organism to the host cell. By studying cases of diarrhoea caused by E. coli researchers were able to uncover evidence of the specific interaction between the gut layer and the pathogen.
• E. coli has also provided researchers with a working model of a long whip-like propeller called 'flagella'. By rotating on its axis, this structure gives a bacteria its motility, and thus its ability reach different regions of its microenvironment, which is crucial in a struggle for survival that can mean life or death for a microbe.

Conclusion

Escherichia coli is a nasty, brain-infecting, bladder-colonising, intestine-attacking, pneumonia-causing, horrible little bacterial pest. It is the root cause of a lot of human illness and suffering and because of this has a right rotten reputation amongst the general public.

E. coli isn't a completely malevolent creature however. There is a flipside to the death and misery it wreaks. E. coli is the best understood bacteria, a scientific model for all life and as such has had a leading role in vastly increasing our understanding of the living world. E. coli is a vital inhabitant of our intestines, which both aids digestions and protects from other infections. E. coli is a keystone of the world's ecosystems. E. coli is a very useful tool for the biological sciences, most notably the remarkable technique of genetic engineering, which ushered in a new dawn in pharmaceutical research and development.

Is the bacterium E. coli a friend, or is it a foe? As this entry demonstrates, it's most certainly both.

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¹ That's enough said on that matter.
² A general name for the irritation and inflammation of the digestive tract.
³ Otherwise known as blood poisoning.
⁴ Antigens are molecules that stimulate an immune response.
⁵ The human body contains about 1x10¹⁴ cells (that's a 1 followed by 14 zeros), 10% of which actually belong to us.
⁶ Which is more commonly known as 'poo'.
⁷ Although genetic predisposition also plays a role in determining if a person is lactose-tolerant or otherwise.
⁸ 'Water, water everywhere and all the boards did shrink; Water, water everywhere, nor any drop to drink.' - Rime of the Ancient Mariner by Samuel Taylor Coleridge
⁹ Which was named after the Chimaera; a mythological beast with the head of a goat, body of a goat, and tail of a serpent.