Investigating Klebsiella pneumoniae pathoadaptation at the mucosal surface using human-derived organoids

• Applicant: Dr. Miro Thorsten Wilhelm Plum, Ph.D.
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Metabolism, Biochemistry and Genetics of Microorganisms ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562169108

This project explores how Klebsiella pneumoniae can exist harmlessly in the gut but become a dangerous pathogen in the lungs. The aim is to uncover how this bacterium interacts with the protective mucus in the lungs and gut, adapts to different environments, and overcomes the body's defenses. Key questions include how K. pneumoniae uses lung and gut mucus for nutrients, attaches to tissues, and how this mucosal adaptation leads to virulence in the lung. To investigate this, the study uses human-derived organoid models, miniature versions of the lung and gut grown in the lab. These models mimic human tissue more accurately than traditional methods and allow studying bacterial behavior in high-resolution. The project has two main goals: first, to identify the bacterial genes and processes that help K. pneumoniae colonize lung and gut tissues, and second, to understand how the bacterium adapts to these environments and becomes harmful in the lungs. By combining advanced techniques like live fluorescence microscopy, transposon screening, and RNA sequencing, this research will uncover the key factors behind K. pneumonia’s ability to switch between harmless and harmful states. These findings will fill critical gaps in our understanding of K. pneumoniae and deepen our knowledge of how the colonization of different mucosal tissues can lead to virulence.

• DFG Programme: WBP Fellowship
• International Connection: Switzerland
• Host: Professor Alexandre Persat