On an intruiging E. coli strain....

Escherichia coli bacteria have a dubious reputation when it comes to our health. Usually you will find them referred to in the news as E. coli after another outbreak occurred. However, a multitude of E. coli bacteria exist! Indeed, some are "pathogenic" and can cause dismay when we accidentally get them into our gastro-intestinal or urinary tract. Other bacteria are "commensal" and are actually normal inhabitants of our gut and doing us no harm as long as they stay where they are. And, intriguingly, so-called "probiotic" bacteria exist that can produce factors promoting our health, for example by killing pathogenic bacteria. This story is about a strain that falls into the last category: E. coli Nissle 1917. To understand its name we have to go back just over 100 years back in history....

It was during the First World War that a German medic and scientist Alfred Nissle (hint!) became interested in how the human host and its bacterial inhabitants interact: what factors determine health and disease for the human and what is a healthy microbial community? A simple way to test the influence of one bacteria to the other is to grow them together on a petri-dish and see what happens.... Ulrich Sonnenborn, a leading scientist in Nissle research, nicely describes how Alfred Nissle designed a test to find bacterial strains in our stool samples that could impede the growth of pathogenic Salmonella bacteria. Indeed, he observed that sometimes the pathogens would hardly grow and particular E. coli strains were thriving. It was in 1917 (another hint!) when Alfred Nissle isolated the strain we now know as Nissle 1917 from the stool of a German soldier that - unlike many comrades - did not suffer from the heavy then often fatal bloody diarrheas caused by Shigella bacteria. After testing many strains present in his stool - and thus gut - Alfred Nissle found the strain with the best health promoting activities.

Unsurprisingly, this little creature has been extensively studied over the past 100 years in the hope to unlock its secret health promoting powers! Still, we now, for the first time, report the results of a so-called untargeted metabolomics study that investigated whether we could find any differences in metabolic capacities of E. coli Nissle and its close relatives. Using mass spectrometry techniques, we measured the metabolic output from Nissle 1917 and closely related E. coli strains including pathogens and commensals. The outcomes were remarkable as the small molecule output of Nissle 1917 was very different from genetically very similar strains only differing in a few hundreds of hypothetical proteins. These not yet functionally described proteins may well be responsible for Nissle's unique metabolic capacities. Furthermore, this could potentially explain part of its ascribed probiotic characteristics next to known factors as microcins which are antibacterial peptides active under low-iron conditions typically for an inflamed gut.

We show how Nissle excretes the small molecules Citrulline and Ornthine into its environment and also takes up more Arginine - one of the amino acids - than the other strains studied do. These other strains were found to emit the structurally close yet different Arginic acid. All these molecules bear similarities and are present in the Arginine biosynthesis pathway in bacteria. We also detected the presence of a not previously described bacterial metabolite that could well be part of the same metabolic pathway as it shares functional groups with Citrulline and Arginic acid. In the Figure below you see examples of mass spectrometry data analysed and the proposed molecular structures. Yes indeed, it is from those kind of spectra that I try to derive the chemical structures of small molecules.

This fascinating bug has been turned into an over-the-counter medicine. Perhaps surprisingly, this was already done by Alfred Nissle himself! He coined it Mutaflor after the Latin words "mutare" and "flora" which in this context would translate as "changing the intestinal microflora". Moreover, recent studies show that by taking advantage of modern metabolic engineering techniques applied to Nissle 1917, it can be used to our advantage in even more situations. Here, the modified bug were shown to help to reduce levels of toxic ammonia in our blood.

Just after the centenary year of E. coli Nissle 1917 the research into its remarkable properties remain very much active. Our study contributes to the legacy of Alfred Nissle who foresaw that not all E. coli strains are our enemies and we hope to inspire more research into the effect of small molecules excreted by gut bacteria and their impact on disease and health.