Author: Liliana Sánchez Rocha
Read time: 8 minutes
Throughout the ImmunoWars E. coli saga, we’ve explored both its sinister and beneficial sides. But, did you know that this tiny bacterium has revolutionized biotechnology? Yes! This little creature has not only been used as a tool to uncover the hidden secrets of life, but it has also provided invaluable molecular tactics. Tactics that may have the potential to treat some of the most feared diseases; like cancer, do you want to know how?
From trash to fame: how did E. coli become a model?
In 1885, Theodor Escherich described a bacterium that was very resilient and easy to work with under the conditions of a laboratory back in those days(1). which bacteria it was? No other than Escherichia coli (E. coli). But what made it so easy to work with?
- Availability: No need to look “Far, Far Away,” E. coli is a permanent resident of all mammals’ gut, as such, it’s very frequently released to the outside world, so you know where to look for it(1).
- Fast replication: Imagine needing coffee and having to wait 24 excruciating hours at the coffee machine. Bacterial replication in the lab is like waiting for the precious caffeine to move on with the research. It comes in handy that E. coli can divide in just 20 minutes under lab conditions(2). Is it the fastest? No, Vibrio natriegens can replicate in just 10 minutes! (3) On the other extreme, we have Mycobacterium tuberculosis with 22 to 24 hours(4), or what about Anammox bacteria, which can take from 10 to 14 DAYS(5).
- Adaptability: E. coli can grow with and without oxygen! This change in metabolism enables it to use different sources of energy like glucose, lactose, maltose, glycerol(6), and even those that could be toxic to other bacteria, like acetate(2, 7). What does this mean? Imagine a super-human that could eat and survive also on wood, plastic, or even toxic waste. That is E. coli, the cockroach of the microbial world.
- Natural variability: The E. coli family is highly diverse! How big? Ongoing discoveries and classifications change the numbers constantly, but the National Center for Biotechnology Information (NCBI) lists thousands of E. coli strains(8). Despite its reputation, most of the members are non-pathogenic, making it ideal and safe to explore in the lab(1).
- Simple genome structure: The length of the genome is measured by base pairs (bp), each bp could be seen as a piece of a gigantic puzzle to discover how life happens. Humans have nearly 3 billion bp, can you imagine solving a 3-billion-piece puzzle? E. coli is a thousand times less complex with only 4.6 million bp although not the shortest, that one is Candidatus Carsonella ruddii with 173,904 bp (9, 10).
Regardless of not being the fastest or with the smallest genome, the combination of all these characteristics turned E. coli into a magnificent biological model in which some secrets of life were revealed. Let's dive deeper into some of them...
Was E. coli the whistleblower of conjugation and antibiotic resistance secrets?
In 1946, researchers Lederberg and Tatum used E. coli to open one of the most hidden secrets of the bacterial world: the exchange of DNA material between bacteria, known as “conjugation.” Before, it was believed that bacteria duplicated as a clone without much DNA variation. Conjugation became essential in understanding bacterial evolution and how antibiotic resistance is speeding up in the micro world, a key concern that keeps hunting modern medicine (11, 12). So yes, E. coli is not only a biotech hero but also a whistleblower.
How did E. coli help in understanding and cracking the code of life?
The Meselson-Stahl Experiment (1958) resulted in understanding how DNA is duplicated and passed down to the next generation (semiconservative model). However, the story did not end there, but in the early 1960s thanks to Marshall Nirenberg and Heinrich Matthaei. They used E. coli’s extracts to decipher how the sequences of RNA served as a template to translate genetic information into specific amino acids. Just like deciphering Egyptian hieroglyphs, these findings were the beginning of learning the language of life(11, 12).
How was E. coli turned into a medicine factory?
In 1973, scientists Stanley Cohen and Herbert Boyer wondered if it was possible to introduce foreign DNA to E. coli. If so, could the bacteria follow these instructions to use this DNA to produce this foreign protein? After multiple experiments, genes taken from the clawed frog were successfully inserted into E. coli. The results? The desired frog protein!(13). This ignited even more questions; could E. coli also produce human proteins? Suddenly the opportunities were immense, and the world witnessed the beginnings of “Genetic engineering.” E. coli then was engineered to become one of the most important medicine providers for diabetes type II patients(14).
How is E. coli saving lives?
History tells that before discovering insulin, diabetes type II patients’ only treatment was restrictive diets of just 450 calories a day! Could you survive on just one bagel with cream cheese a day? No! Neither could they... By 1910, the disease was linked to the lack of insulin, and the goal became to obtain it for treatments. Extracted from animals at first, this posed ethical and efficacy challenges. But thanks to genetic engineering, E. coli was given instructions to produce human insulin. Through a process kind of similar to making beer, E. coli has become the “insulin brewer” saving lives since 1982 (15).
Can E. coli help edit your genetic fate with CRISPR-Cas?
Does E. coli have any secret weapon hidden in its DNA? It does! It has been named “CRISPR-Cas.” First observed by Yoshizumi Ishino in 1987, it was not until 2007 that Philippe Horvath and colleagues figured out that bacteria have their own type of “immune system” and CRISPR-Cas is part of it. CRISPR-CAS can be seen as a system of tiny molecular scissors that seek for damaged DNA to snip it away and protect the bacteria. What does this mean to us? It could help us edit our medical fate and not fear genetic diseases anymore. It may one day even prevent some types of cancers like leukemia and lymphoma(16).
How has E. coli taught us about evolution?
Since 1988, an ongoing experiment led by Dr. Richard Lenski has tracked E. coli through 80,000 generations. Perhaps you wonder, why just 80,000 generations in the last 37 years? Can’t E. coli divide in just only 20 minutes as we have read before? Math ain’t mathing! In this experiment, the bacteria do not divide nonstop, instead, scientists limit nutrients and transfer only 1% daily, slowing growth and mimicking natural selection rather than unlimited division. Quality over quantity! Replicating such a study in humans would take over 2 million years! E. coli’s rapid replication has allowed us to witness adaptation and genetic evolution within our lifetime(17-19).
The end of the E. coli saga
Thanks to the study of the microbial world’s tricks, life has been decoded, evolution has been witnessed in real time, bacterial DNA exchange was discovered, life-saving treatments have been developed, and many other biotechnologies are still emerging at this right moment.
So, next time you play ImmunoWars and unleash E. coli power on your opponents, remember there’s more to E. coli than just meets the eye… or microscope ;)
Want to play with E. coli? Click here!
References:
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