Pandoraea bacteria, named after teh mythical Pandora’s box, have historically been associated with potential health risks.However, recent research has revealed a surprising twist: these bacteria also possess beneficial properties. “We have been working with an antibiotic-resistant bacterium,” says Elena Herzog, the first author of a study on the topic. Herzog, a doctoral researcher in the team of Christian Hertweck at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), notes that “Pandoraea bacteria not only harbor risks. They also produce natural products with an antibacterial effect.”

Despite their potential pathogenicity, the molecular characteristics of Pandoraea remained largely unexplored. “We only knew that these bacteria occur in nature and that they can be pathogenic because they have been found in the lung microbiome of patients with cystic fibrosis or sepsis,” explains Herzog.

Iron Acquisition: A Key to Survival

Iron is crucial for the survival of most organisms, including bacteria. “Iron plays a central role in enzymes and the respiratory chain of living organisms, such as,” explains Herzog. Though, acquiring iron in environments like the human body is challenging. To overcome this, many microorganisms produce siderophores, which are small molecules that capture and transport iron into the cell.

The research team aimed to identify the factors that enable Pandoraea strains to thrive in competitive environments, given the lack of previously known virulence or niche factors. “However, there were no known virulence or niche factors in the Pandoraea bacteria that could help them survive,” says Herzog.

Through bioinformatic analyses, the team discovered a previously unknown gene cluster called pan, which codes for a non-ribosomal peptide synthetase, an enzyme typically involved in siderophore production.”We started with a gene cluster analysis and specifically searched for genes that could be responsible for the production of siderophores,” reports Herzog.

By inactivating specific genes and employing advanced analytical techniques, including mass spectrometry and NMR spectroscopy, the researchers isolated and characterized two new natural products: Pandorabactin A and B. These molecules can bind iron and are believed to play a significant role in the survival of Pandoraea strains. “The molecules help the bacteria to take up iron when it is scarce in their surroundings,” says herzog.

“We have been working with an antibiotic-resistant bacterium… Pandoraea bacteria not only harbor risks.they also produce natural products with an antibacterial effect.”

Pandorabactins: Inhibiting Competitors

Further experiments revealed that pandorabactins inhibit the growth of othre bacteria, such as Pseudomonas, Mycobacterium, and Stenotrophomonas, by depriving them of iron.

Analyses of lung sputum samples from cystic fibrosis patients showed a correlation between the presence of the pan gene cluster and changes in the lung microbiome, suggesting that pandorabactins can directly influence microbial communities in diseased lungs.

While medical applications are still distant, this discovery sheds light on the survival mechanisms of Pandoraea bacteria and their interactions within the human body. “However, it is still too early to derive medical applications from these findings,” emphasizes Herzog. “Nevertheless, the discovery provides important details on the survival strategies