27-Apr-2022 - Max-Planck-Institute für terrestrische Mikrobiologie

Finding new weapons in Nature`s battlesites

Genomic studies open up a wealth of bioactive small molecules in insect-killing bacteria

Interactions between microbes and other organisms are mediated by a plethora of small molecules, also called natural products. A research team led by Dr. Yi-Ming Shi and Prof. Helge Bode from the Max Planck Institute for Terrestrial Microbiology has now performed a systematic analysis of biosynthetic ‘dark matter’ and biological functions, thus creating a solid basis for future discovery and refinement of natural products.

When bacteria interact with other organisms, a myriad of bacterial natural products are involved. In most cases, it is not possible to trace which bacterial strain produces which natural substance and what properties it has. And thus products such as colibactin from human intestinal bacteria involved in cancer development remain the exception rather than the rule.

Insect pathogenic bacteria: Research models with great potential

Xenorhabdus and Photorhabdus live in symbiosis with specific nematodes. Jointly, they infect and kill soil-dwelling insect larvae. Within this relationship, the bacteria are responsible for the production of numerous toxins and other interaction-mediating substances. At the same time, they can be cultured and genetically manipulated in the laboratory in the absence of their nematode host. Therefore, they are considered promising research models for studying the chemical ecology of bacterial natural products.

Now, for the first time, the bacteria have been systematically studied in a combination of pangenomic and domain sequence similarity analysis with respect to two central questions: which gene clusters are responsible for natural product production, and are they evolutionarily conserved or unique to these bacterial genera?

Numerous unknown biosynthetic gene clusters discovered

The researchers led by Dr. Yi-Ming Shi and Prof. Dr. Helge Bode identified 1,000 biosynthetic gene clusters, over half of which are previously unknown. Using homologous expression and chemical structure analysis the research team uncovered a veritable biochemical treasure trove. But what does the nematode host benefit from these bacterial substances?

“Our bioactivity evaluation demonstrates that the prevalent compounds are eukaryotic proteasome inhibitors that presumably suppress the immune system of insects, but we identified also other virulence factors against insects or suppressors of the insect immune system. Thus our findings account for the molecular functional basis of these bacterial natural products,” says Yi-Ming Shi, first and correspondence author of the publication. “Among the new discoveries, many natural products stand out not only due to their unusual chemical structural features and modes of action, but also their prevalence across different bacteria taxa. This implies possible universal chemical weapons in bacteria.”

Bacteria with special abilities to produce natural substances

Identification and functional characterization, which were performed in cooperation with Prof. Yonggyun Kim from Andong National University (Korea), Prof. Michael Groll from Technical University of Munich, and Prof. Rolf Müller from Helmholtz Institute for Pharmaceutical Research Saarland, revealed how bacteria orchestrate the interplay of natural products to maintain their symbiotic lifestyles, while pointing to the enormous capabilities of the genus Xenorhabdus in particular to produce novel natural products for drug leads. As such, however, this work also lays important groundwork for significantly accelerating the discovery and refinement of natural products in microbiomes from other niches.

  • Shi, Y.-M.; Hirschmann, M.; Shi, Y-N.; Ahmed, S.; Abebew, D.; Tobias, N.J.; Grün, P.; Crames, J.P.; Pöschel, L.; Kuttenlochner, W.; Richter, C.; Herrmann, J.; Müller, R.; Thanwisai, A; Pidot, S. J.; Stinear, T. P.; Groll, M.; Kim, Y.; Bode, H. B.; Global analysis of biosynthetic gene clusters reveals conserved and unique natural products in entomopathogenic nematode-symbiotic bacteria; Nature Chemistry 14 (2022)

Facts, background information, dossiers

  • natural products
  • bacteria
  • biosynthesis
  • nematodes
  • insects
  • virulence factors

More about Max-Planck-Institute für terrestrische Mikrobiologie

  • News

    Environmentally friendly production of mandelic acid

    Sometimes potentially useful enzymes are not easy to discover because their biocatalytic capabilities may go beyond their natural and thus known range of action. By recombining a newly discovered enzymatic capability, a research team from the Max Planck Institute for Terrestrial Microbiolog ... more

    Synchro swimmers under the microscope

    Not only birds, fish and even crowds of people show collective movement patterns, motile bacteria also form currents and vortices when their cell density exceeds a certain size. Researchers at the Max Planck Institute for terrestrial Microbiology in Marburg have now been able to show how sw ... more

    Pathogens from the sea

    Vibrio parahaemolyticus can be found in the tidal zones in estuarine areas. The marine bacterium causes acute gastroenteritis in humans and is the leading cause for seafood borne illnesses in the world. Researchers from the Max Planck Institute for terrestrial Microbiology in Marburg, Germa ... more

More about Max-Planck-Gesellschaft

  • News

    Pumping up the music of molecules

    Sensitive animal noses can sniff out trace particles, such as volatile organic compounds, in the ambient air. Humans, on the other hand, are developing innovative technologies for this purpose, such as optical spectroscopy. This uses laser light to detect the molecular composition of gases. ... more

    How to find marker genes in cell clusters

    The thousands of cells in a biological sample are all different and can be analyzed individually, cell by cell. Based on their gene activity, they can be sorted into clusters. But which genes are particularly characteristic of a given cluster, i.e. what are its “marker genes”? A new statist ... more

    Cell-culture breakthrough: Advanced “mini brains” in the dish

    “Outer Radial Glia” (oRG) cells are nervous system stem cells that are instrumental for the development of the human cortex and have been challenging to produce in the lab. Now, a team of Max Planck researchers from Berlin succeeded in generating brain organoids that are enriched with these ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: