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Study provides deeper insight into the regulation of bacterial toxins

In nature, different organisms often live in symbiosis - and thus benefit from each other. This also applies to certain threadworms, which kill their prey together with bacteria. As soon as the nematodes have penetrated their prey, preferably insect larvae, the bacteria from their intestines take over and kill the larva with the toxic substances. Helpful side effect: the poisoned larva are spurned by competitors in their search for food. A team of scientists from Frankfurt am Main and Jena has now identified a regulator that significantly influences the biological processes taking place during this prey migration. The joint publication is available online at the journal Nature Microbiology.

The bacteria that support the nematodes with their venom originate from the genera Photorhabdus and Xenorhabdus. Together they form a so-called obligatory symbiosis; both partners are bound to each other and cannot exist in nature without the other. While the nematode benefits from the toxin production of its bacterium, the intestinal bacterium is given a protected and suitable habitat. There it then produces a complex mixture of different molecules, so-called secondary metabolites, which in this case have a toxic effect.

Secondary metabolites also play an important role in human medicine. For example, many of the antibiotics and cancer drugs used clinically are based on bacterial secondary metabolites.

How the formation of this cocktail of secondary metabolites is regulated has already been partially researched, but not the role of small ribonucleic acids (sRNA) in this process. These exist in almost all organisms and play an important role in controlling protein production. The scientists involved in the study have now been able to demonstrate a decisive involvement of these sRNAs in the production of secondary metabolites: The sRNA known as "ArcZ" influences about 15 percent of all genes in the bacteria - including all genes that are involved in the formation of secondary metabolites.

"The production of secondary metabolites seems to depend on ArcZ in many other bacterial genera as well," explains Helge Bode, Professor of Molecular Biotechnology at the Goethe University Frankfurt and the LOEWE Center for Translational Biodiversity Genomics (TBG). "By elucidating the underlying mechanism, we are now able to produce new secondary metabolites in these bacteria in a targeted manner, which could possibly be used clinically in the future," adds Nick Neubacher, PhD student and first author of the publication.

"Our work thus links two research areas that have had virtually no contact so far: research on regulatory RNAs and on secondary metabolites," explains Kai Papenfort, Professor of General Microbiology at the University of Jena and its Cluster of Excellence “Balance of the Microverse”.

This research is a close teamwork of scientists from various disciplines under the leadership of the Collaborative Research Center 902 "Molecular Principles of RNA-based Regulation" of the German Research Foundation, and was additionally supported by the Cluster of Excellence 2051 "Balance of the Microverse" and the LOEWE Center for Translational Biodiversity Genomics (TBG).

Original publication

Nick Neubacher, Nicholas J. Tobias, Michaela Huber, Xiaofeng Cai, Timo Glatter, Sacha J. Pidot, Timothy P. Stinear, Anna Lena Lütticke, Kai Papenfort and Helge B. Bode (2020): Symbiosis, virulence and natural-product biosynthesis in entomopathogenic bacteria are regulated by a small RNA. Nature Microbiology, https://www.nature.com/articles/s41564-020-00797-5

Text: Stephanie Mayer-Bömoser & Alena Gold
Photo: D. Kucharski, K. Kucharska/Shutterstock.com