How E. coli Rose to Prominence
by Roberto
Figure 1. Anything found to be true of E. coli must also be true of Elephants. Source. Frontispiece: E. coli with phages. Source
I could not help it, I had to include the word "rose" in the title of this post. The reason? I was driven to do so inspired by a remarkable bit of investigative reporting by Memo Berkmen and Paul Riggs posted in STC in 2016. Therein they describe their heroic – even if failed – attempts at determining how E. coli K‑12 got its name. They call themselves "...lovers of that sour smelling E. coli..." after quoting from that immortal tale of lovers, Shakespeare's Romeo and Juliet:
"What's in a name? That which we call a rose
By any other name would smell as sweet."
Even though my "rose" is the verb and not the noun, I hope you'll find this story just as sweet. While Memo and Paul sought the origin of a name of the most famous of all E. coli strains, I have sought details of how a puny inhabitant of the human gut rose to such prominence in molecular biology.
This post was inspired by last week's Talmudic Question #191 contributed by Michael Malamy. I felt that an equally Talmudic question is this one: Being such a puny gut microbe (outnumbered by anaerobes by >1000 to 1), how did E. coli rise to such prominence in molecular biology? A prominence that is summed up in the well-known aphorism attributed to Jacques Monod: "Tout ce qui est vrai pour le Colibacille est vrai pour l'éléphant." (Before I elaborate in the rise of E. coli, I need to interject a note of gratitude. It was Dianne Newman who first brought to my attention the fact that this quote is elaborated from a statement coined earlier by Jan Kluyver in describing the unity of biochemistry: "from elephant to butyric acid bacterium—it is all the same." For that and so much more, many thanks!)
Figure 2. Escherich's habilitation treatise. Source
The first description of E. coli is found in Theodor Escherich's habilitation treatise, Die Darmbakterien des Säuglings und ihre Beziehungen zur Physiologie der Verdauung (Enterobacteria of infants and their relation to digestion physiology). It was published in 1886 and established Escherich as the first pedriatic infectious disease physician. In the text, Escherich describes a bacterium commonly isolated from the feces of healthy neonates and names it Bacterium coli commune. Its relative abundance in neonates versus adults, its rapid growth rate and the "not-so-strict" anaerobic culture conditions he used probably all contributed to this bacterium outgrowing the far more numerous anaerobes present in the gut. By 1895 such isolates were re-named Bacillus coli, simply because they were rods (Bacillus — from the Latin baculus = stick). The genus Escherichia – in honor of the discoverer – was established in 1919 by Castellani and Chalmers and presented in their astonishing tome Manual of Tropical Medicine. A peak at that publication will be very much worth your while! And for a comprehensive treatment of Escherich's accomplishments along with detailed accounts of early work with E. coli, I highly recommend the EcoSal chapter "Escherich and Escherichia" by Herbert C. Friedmann.
The first adumbrations that E. coli would rise to play a key role in the birth of molecular biology occurred early in the twentieth century. In 1907, Rudolf Massini – working in Paul Ehrlich's Institute for Experimental Therapy in Frankfurt, Germany – published a paper (as cited here) characterizing a strain of E. coli which started as a lactose non-fermenter. Upon prolonged incubation on lactose indicator medium, Lac+ papillae appeared within the Lac– colonies. Progeny from the papillae remained Lac+ after re-streaking. Massini called the strain Bacillus coli mutabile. In his own words: "This work constitutes a contribution from bacteriology to the theory of mutation," suggesting (at least in a retrospective interpretation) that E. coli might be amenable to genetic analyses. Massini was thus way ahead of his time by doing these sorts of bacterial genetics.
Figure 3. Example of a colony with papillae. Source
E. coli was also central in the early work with bacteriophages. In my reading of Twort's 1915 description of "ultra-microscopic viruses" (i.e., the paper noted as documenting the discovery of bacteriophages), it is possible that in instances he could have been working with isolates of Bacillus coli. Regardless, when in the early 1920s André Gratia rediscovered Twort's original work he began using E. coli. Gratia was also ahead of his time, in many respects a pioneer of E. coli genetics. For example, in 1925 he published his discovery of the production of an antimicrobial substance from E. coli, Colicin V, years before Fleming's account of penicillin. Thus, by the 1920s the stage was set. Escherichia coli had its proper name and numerous researchers interested in understanding it. How was it that in the next twenty years E. coli would rise to center stage in the drama of the birth of molecular biology? In my view, this was a play in three acts: the Phage Group, the French School, and the Lederbergs. These are the stuff of legends and much has been written about all three. Here I want to simply relate the way each group came to choose to work with E. coli.
By most accounts, the Phage Group came together in the late 1930s through the interactions of Alfred Hershey, Salvador Luria and Max Delbrück. Hershey and Luria had previous training in phage work. But it was Delbrück's bringing in the use of E. coli and its phages that solidified the group. Delbrück's choice is a story of being at the right place at the right time and seizing the opportunity. Delbrück had trained as a theoretical physicist in Germany and having gained an interest in genes, went to Caltech in 1937 set to work on Drosophila genetics with Thomas Morgan. After six frustrating months given the slow pace of that model system, he was attracted to the work that Emory Ellis was doing with the bacteriophages as a way to understand the basic biology of viruses that could be involved in cancer. Ellis and his wife Marion had set up a system using phage obtained from the Pasadena sewage treatment plant. Here's the clincher. As a bacterial host they were using E. coli! Why? Simply because it was available from Carl Lindegren, a student in Morgan's group. In a way, Delbrück was handed E. coli on a silver platter. But he certainly knew how to run with it and that he did. By 1943, he and Luria had published their landmark paper on the origin of mutants and in so doing had used E. coli to give birth to microbial genetics.
As wonderfully related by Agnes Ullmann, the French School of Molecular Biology was led by André Lwoff, Jacques Monod, and François Jacob. How they came to focus on E. coli also has an amusing anecdote. At about the time that Delbrück arrived at Caltech (1937) Monod was leaving Caltech after a short visit with Morgan's group. Monod then took a faculty position at the Sorbonne in Paris. Importantly, he often met with Lwoff. (Monod's visit to Caltech proved lifesaving, the details of why you'll have to read in Ullmann's essay.) Lwoff relates how he introduced Monod to E. coli: "I advised him to use a bacterium able to grow in a synthetic medium, for example Escherichia coli. 'Is it pathogenic?' asked Jacques. The answer being satisfactory, Monod began, in 1937, to play with E. coli and this was the origin of everything..." Everything indeed! By 1940 Monod had discovered diauxic growth, marking the beginning of a long friendship with lactose and E. coli.
The arrival of the Lederbergs to the E. coli scene came a little later. But what a bang they created! In 1946 Joshua Lederberg and Edward Tatum published their discovery of gene recombination in E. coli, breaking wide open the field of E. coli genetics. This was the first of many enormous contributions that Josh made to molecular biology using this bacterium. Not long after, in 1950, Esther Lederberg discovered the lysogenic phage lambda, which would soon parallel the lac operon in terms of providing insights into gene regulation. Both of these seminal discoveries were done using E. coli K‑12. The STC post searching for how that strain got its name already follows its history from Stanford to the Lederbergs. What bears repeating here is the incredible strike of luck they had to be using a strain that had two unusual traits: a derepressed conjugative and integrative plasmid (F) that allowed the detection of recombination and the prophage lambda.
The rest is, as they say, history!
