Biodiversity: Foundation for New Drug Discoveries

Helmholtz Centre for Infection Research

The threat posed by antibiotic resistance is growing worldwide. Research into new active compounds is therefore of the utmost importance to ensure that bacterial infections can continue to be treated effectively in the future. Natural compounds play a crucial role in this regard. Compared to other microorganisms, myxobacteria remain relatively unexplored, which increases the likelihood of interesting discoveries. After all, the greater the biological diversity of the bacteria studied, the greater the chance that they produce previously unknown candidate active compounds. In the published study, the researchers describe 118 new myxobacteria, as well as their sequenced genomes. In doing so, they significantly expand the available genomic resources. HIPS is a site of the Helmholtz Centre for Infection Research (HZI) in collaboration with Saarland University.

Until now, only eleven families and 32 genera were known within the order of myxobacteria. A team led by Prof. Rolf Müller, Scientific Director of HIPS and head of the department "Microbial Natural Products", collected soil samples over several decades and isolated primarily myxobacteria from them. They were also supported in this effort by citizen scientists participating in the Microbelix citizen science campaign. As a result, they were able to expand the diversity of these promising natural product producers to 28 families and 90 genera. In addition, the researchers sequenced the genomes of all newly described myxobacteria. "The newly isolated bacteria and their genome sequences offer us a rich treasure trove of novel natural products and their genetic blueprints. In virtually every genome analyzed, we find multiple gene sequences for the production of potential active compounds that no one has ever seen before—that's incredibly exciting," says Dr Ronald Garcia, a scientist in the "Microbial Natural Products" department.

To enable researchers worldwide to use this data, the HIPS team has made ABC-Myxo available: an interactive, web-based atlas of the gene regions that myxobacteria use to produce active compounds. The service is available free of charge to researchers around the world. In the future, the bacteria themselves will be maintained for research purposes by the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures.

The research team was also able to demonstrate that new natural compounds can indeed be derived from the bacteria and their genetic information. In their study, they describe five new classes of compounds: Myxoquaterines are effective against fungi, sandacrabines against viruses, and sandarazoles have antibacterial effects. In addition, new sorangibactin siderophores were discovered, as well as pyxidicyclines, a novel class of topoisomerase inhibitors. "Our data impressively demonstrate how important microbial biodiversity is for the discovery of new natural and active compounds," says Müller. "Hardly any new compounds can be found in microorganisms that have already been well studied. Our myxobacterial collection, on the other hand, offers unparalleled potential for discovering truly novel chemical structures. It thus lays the foundation for urgently needed active compounds to effectively treat infectious diseases in the future as well."

Even interested members of the general public can help to continually expand the diversity of the myxobacteria being studied: As part of the Microbelix participatory project, anyone interested can collect soil samples from near-natural areas, send them to researchers at HIPS, and thus contribute to the discovery of new active compounds. www.microbelix.de

Original publication:

Amay Ajaykumar Agrawal, Ronald Garcia, Guangyi Chen, Chantal D. Bader, Peter Sullivan, Alexander Popoff, Daniel Krug, Maja Hunter, Sebastian Walesch, Emilia Oueis, Christine Frank, Haowen Zhao, Joachim J. Hug, Sebastian Keller, Pascal Hirsch, Azat Tagirdzhanov, Tatiana Malygina, Mary Victory E. Gutierrez, Alexey Gurevich, Judith Boldt, Boyke Bunk, Jörg Overmann, Ulrich Nübel, Andreas Keller, Olga V. Kalinina, Rolf Müller: Unveiling the Taxonomic Diversity and Unprecedented Biosynthetic Treasure of the Phylum Myxococcota. Advanced Science (2026); http://doi.org/10.1002/advs.76919

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