New drugs from toxic birds

Investigation of the symbiosis between bacteria and birds leads to the discovery of new natural products with antimicrobial properties.

Bacteria are a valuable source for the discovery of natural products that can be used for the development of new drugs. A HIPS research team has now identified two new classes of active substances with antimicrobial properties from bacteria that live in symbiosis with a toxic bird. This strategy and the substances discovered offer promising avenues towards the development of new anti-infectives, particularly against antibiotic-resistant pathogens. The researchers published their findings in the journal Nature Communications.

The New Guinea-based regent whistler, or Pachycephala schlegelii in Latin, is a strange bird. It carries batrachotoxin in its black and yellow plumage: a potent neurotoxin, also used by poison dart frogs to effectively protect themselves from predators. This toxin is not produced by the birds themselves, but is enriched from insects that serve as food. Researchers at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), together with international partners, have now discovered that the plumage of the regent whistler contains other substances that protect it from infestation by unwanted microorganisms. Unlike batrachotoxin, however, these substances are not ingested with food, but are produced by bacteria that live in symbiosis with the bird. The HIPS is a site of the Helmholtz Centre for Infection Research (HZI) in collaboration with Saarland University.

An international team led by Christine Beemelmanns, HIPS Department Head and Professor of Medical-Pharmaceutical Microbiota Research at Saarland University, isolated these bacteria of the genus Amycolatopsis from the secretions of the so-called brush gland, a skin gland of the bird. The researchers were able to discover previously unknown bioactive substances in these bacteria, including two new classes of natural products: pachycephalamides and demiguisines. “The discovery of these previously unknown molecules from the microbiome of a bird illustrates the enormous potential that symbiotic relationships offer for the identification of new natural products,” explains Elena Seibel, first author of the study. “Where different organisms live together, there are always interactions. In the case of microorganisms, this communication takes place with the help of chemical signals.” Natural products discovered in this way not only help to better understand the interaction between two organisms, but can also contribute to the development of new anti-infectives.

This innovative approach, in which microbial communities (also known as microbiota) serve as a source of new active substances, is at the core of Christine Beemelmann’s research. Together with her team, she is working on the discovery and functional analysis of new anti-infective natural products from microbiota. Using co-cultivation studies and cell-based assays, the researchers were able to show that the substances produced by the bacteria in the brush gland have an antimicrobial effect. In particular, the new compounds act against keratinolytic bacteria and fungi that attack the skin and feathers of birds.

“Our work impressively demonstrates that the identification of new bioactive natural products from microbial communities is a promising source for the discovery of innovative anti-infectives,” explains Beemelmanns. “The newly discovered natural products, especially the lipopeptides and hexapeptides that we found in avian microbiomes, offer great potential for combating infectious diseases.”

Through a combination of genetic and structural analyses, the team was able to decipher the genetic blueprints responsible for the production of these natural products and thus confirm their origin in the symbiotic relationship between bird and bacterium. The identification of such natural products has far-reaching significance, particularly in view of the increasing spread of antimicrobial resistance, which poses a serious challenge to modern medicine. “By unlocking the potential of microorganisms in symbiotic communities, we can develop new therapeutic approaches to fight infections and counter the global resistance problem,” emphasizes Beemelmanns.

Helmholtz Institute for Pharmaceutical Research Saarland:
The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken was founded jointly by the HZI and Saarland University in 2009. Scientists at HIPS develop and employ experimental and computational approaches to provide new active substances against infectious diseases, optimise them for use in humans and investigate how they can best be transported to their site of action in the human body. A special focus of the institute is on microbial natural products from soil bacteria and the human microbiota as well as innovative medicinal chemistry-driven approaches. http://www.helmholtz-hips.de

Helmholtz Centre for Infection Research:
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and other locations in Germany study bacterial and viral infections and the body’s defense mechanisms. They have in-depth expertise in natural product research and its use as a valuable source for novel anti-infectives. As a member of the Helmholtz Association and the German Center for Infection Research (DZIF), the HZI conducts translational research to lay the foundations for the development of novel therapies and vaccines against infectious diseases. http://www.helmholtz-hzi.de

Media contact:
Dr. Yannic Nonnenmacher
PR Manager HIPS
Helmholtz-Institut für Pharmazeutische Forschung Saarland (HIPS)
Tel.: 0681 98806-4500
yannic.nonnenmacher@helmholtz-hips.de

Originalpublikation:

Seibel, E., Um, S., Bodawatta, K.H. et al. Bacteria from the Amycolatopsis genus associated with a toxic bird secrete protective secondary metabolites. Nat Commun 15, 8524 (2024). https://doi.org/10.1038/s41467-024-52316-3

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