University of Tübingen researchers reverse the evolution of a class of antibiotics to gain insights for the development of new drugs. Illustration Anna Voigtländer. Credit: University of Tübingen/CMFI
Key points:
- Researchers reversed the evolution of a class of antibiotics to gain insights for the development of new drugs.
- By tracing the evolution of the antibiotics and their underlying genetic sequences, the researchers were able to replicate some of the pivotal steps required for creating functional molecules in a laboratory setting.
- “Recreating such an ancient molecule was exhilarating, akin to bringing dinosaurs or wooly mammoths back to life.”
To further aid the fight against antibiotic-resistant pathogens, scientists at the University of Tübingen (Germany) have delved into the intricate world of glycopeptide antibiotics—a vital resource—to uncover their evolutionary origins. By uncovering and understanding their evolutionary trajectory, the researchers are looking for insights that could steer the development of future antibiotics.
For the study, published in Nature Communications, the researchers examined the glycopeptide antibiotics teicoplanin and vancomycin, along with related compounds sourced from specific bacterial strains. These compounds, built from amino acids and sugars, disrupt bacterial cell wall construction, ultimately leading to bacterial death. Notably, teicoplanin and vancomycin exhibit this potency against numerous human pathogens.
The scientists first constructed a family tree of known glycopeptide antibiotics, linking their chemical structures via gene clusters that encode their blueprints. Employing bioinformatics algorithms, they deduced a putative ancestral form of these antibiotics, which they dubbed “paleomycin.” By reconstructing the genetic pathways believed to produce paleomycin, the team successfully synthesized the compound, which displayed antibiotic properties in tests.
According to the paper’s results, the core structure of paleomycin mirrors the complexity seen in teicoplanin, while vancomycin exhibits a simpler core.
“We speculate that recent evolution streamlined the latter’s structure, yet its antibiotic function remained unchanged,” said study co-author Nadine Ziemert from the Controlling Microbes to Fight Infections Cluster of Excellence at the University of Tübingen.
By tracing the evolution of the antibiotics and their underlying genetic sequences, the researchers were able to replicate some of the pivotal steps required for creating functional molecules in a laboratory setting.
“Recreating such an ancient molecule was exhilarating, akin to bringing dinosaurs or wooly mammoths back to life,” said Ziemert. “This journey through time revealed profound insights into the evolution of bacterial antibiotic pathways and nature's optimization strategies, leading to modern glycopeptide antibiotics. This provides us with a solid foundation for advancing this crucial antibiotic group using biotechnology.”