How the joint defence mechanism of two bacteria works

In 2021, Pierre Stallforth, Professor of Bioorganic Chemistry and Palaeobiotechnology at the University of Jena, and his team from the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) showed that bacteria of the genera Pseudomonas and Paenibacillus join forces to protect themselves from their predator, an amoeba. Together with the teams led by Prof. Ute Hellmich and Dr Markus Lakemeyer at the University of Jena, the researchers have now been able to show exactly what this defence mechanism looks like. The study was conducted by the Cluster of Excellence »Balance of the Microverse« at the University of Jena and has been published in the »Journal of the American Chemical Society«.

Analysis at the molecular level

The cooperation between the two bacteria Pseudomonas sp. SZ40 and Paenibacillus sp. SZ31 is based on a natural product called syringafactin, which belongs to the class of lipopeptides. It is produced by Pseudomonas, but only becomes dangerous to the amoeba after a modification caused by Paenibacillus. Paenibacillus cleaves the lipopeptide at an unusual site using two special enzymes known as DL peptidases. This converts the syringafactin into a substance that is toxic to the amoeba.

»It was very exciting for me to understand the mechanism by which the special class of DL lipopeptides is cleaved and how this can be exploited in the interaction of microbes«, reports Hellmich. What is special about these natural products is their unusual site of attack in the spatial structure of the lipopeptides.

»Amino acids are normally L-configured in nature, which is why most enzymes are specialized in cleaving this variant«, explains Stallforth. D and L forms differ only in their symmetry; they behave like mirror images of each other. Their atomic composition is the same. »This means that for many analytical methods, both molecules look the same, even though we know that there is a huge difference between using the left or right hand«, Hellmich illustrates.

Multifunctional game mechanics

According to Stallforth, this alteration is not an isolated case, but appears to be a general, albeit very specific, mechanism. »These enzymes are so interesting because we can use them to elucidate the structure of complex natural substances by selectively dividing them into smaller fragments.« »And that will make it easier for us and other groups to analyse new natural substances in the future,« adds Lakemeyer. This is a great help for the development of new natural product-based anti-infectives.

Wonderful cooperation

Not only the bacteria, but also the research teams worked together organically, Hellmich explains enthusiastically. »Individually, none of us would have been able to tackle this problem in this way«, Hellmich describes the situation. »Here in Jena, we were able to go from small natural products to protein structures in cells to the ecological context, and we also had an application in biotechnology.« That is unique. »I have never experienced anything like Jena at any other location«, adds Lakemeyer. »It’s just fun when you can look at the same problem from different angles and then also have great colleagues.«

The study was a collaboration between the Leibniz-HKI and the Universities of Jena and Würzburg. The research networks involved were the Cluster of Excellence »Balance of the Microverse« and the Collaborative Research Centre ChemBioSys, which are also based at the University of Jena.