Pandorabactins: A New Frontier in Understanding Lung Pathogens

In a significant advancement in microbiological research, an interdisciplinary team led by the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) in Jena has uncovered a novel group of bioactive compounds known as pandorabactins, found in pathogenic bacteria of the genus Pandoraea. This discovery, published in the esteemed journal *Angewandte Chemie International Edition* on June 19, 2025, sheds light on how these bacteria compete for vital iron resources in the human lung, a critical factor in their pathogenicity.

The genus Pandoraea, which has been relatively understudied, derives its name from Pandora's box in Greek mythology—a metaphor for the unpredictable dangers it poses. "We have been working with an antibiotic-resistant bacterium," explains Dr. Elena Herzog, the study's lead author and a doctoral researcher at Leibniz-HKI. Despite their health risks, the Pandoraea bacteria are also known to produce natural antibacterial compounds, highlighting a duality in their biological roles.

Iron is an essential element for all living organisms, playing a crucial role in various biological processes, including enzyme functions and cellular respiration. However, in iron-poor environments, such as the human body, the absorption of this vital element becomes challenging. Many microorganisms, therefore, produce siderophores—molecules that effectively bind iron from their surroundings. Prior to this study, no virulence factors or niche determinants had been identified in Pandoraea that would facilitate their survival in such competitive environments.

The research team conducted bioinformatic analyses that led to the identification of a previously unknown gene cluster termed *pan*, responsible for coding a non-ribosomal peptide synthetase, an enzyme integral to siderophore production. "We specifically searched for genes that could be involved in siderophore production," Dr. Herzog states. Using targeted gene inactivation, culture-based methods, and advanced analytical techniques such as mass spectrometry and NMR spectroscopy, the team successfully isolated two new natural products, pandorabactin A and B. These compounds demonstrated the ability to complex iron, suggesting a vital role in the survival of Pandoraea strains in iron-limited environments.

Notably, bioassays indicated that pandorabactins inhibit the growth of competing bacterial species, including Pseudomonas, Mycobacterium, and Stenotrophomonas, by sequestering iron, thereby reducing competition in the lung environment. Furthermore, analyses of sputum samples from cystic fibrosis patients revealed that the presence of the *pan* gene cluster correlates with changes in the lung microbiome, suggesting that pandorabactins may influence microbial community dynamics within diseased lungs.

Despite the promising findings, Dr. Herzog cautions against premature medical applications of these compounds, stating that it is still too early to draw clinical conclusions from the research. Nevertheless, this study is a significant step forward in understanding the competitive survival strategies of Pandoraea bacteria and their impact on the human lung microbiome.

The collaborative research involved institutions such as the University of Jena, University of Heidelberg, and the University of Hong Kong, and was conducted as part of the "Balance of the Microverse" Cluster of Excellence and the ChemBioSys Collaborative Research Center, receiving funding from the German Research Foundation. The imaging mass spectrometer utilized for analyses was supported by the Free State of Thuringia and co-financed by the European Union.

This discovery not only enhances our understanding of microbial interactions in the lung but also opens up avenues for future research into potential therapeutic applications targeting these bacterial survival mechanisms. As the field of microbiology continues to evolve, the role of pandorabactins in health and disease may reveal new strategies for combating antibiotic-resistant infections and improving patient outcomes in respiratory diseases.