Published: 29 August 2024

Meaningful research without animal testing

Antibiotic-resistant germs are particularly feared in hospitals. One of them is Pseudomonas aeruginosa. An infection with this bacterium causes pneumonia, which leads to death in up to 50% of ventilated patients. How the germ overcomes the lung's protective layer and destroys the underlying tissue was previously unclear. Now, researchers at the University of Basel have used a detailed human lung model to decipher the underlying mechanisms (1).

For this purpose, they used so-called mini-lungs, in which they grew human lung cells on a membrane at the interface between air and culture medium(2). The cells formed a tissue composed of different cell types, just like in our lungs. For example, it contains so-called goblet cells, which produce the mucus that lines our lungs. The lung model also has cilia, which are tiny hair-like structures that move rhythmically, thereby transporting the mucus—along with attached foreign particles or bacteria—out of the lungs, thus cleaning and protecting the lung tissue. This model perfectly replicates the protective layer of the human lung. Additionally, the researchers developed a method to track in real-time how pathogens invade the tissue and change in the process (3).

The human mini-lungs were then infected with Pseudomonas aeruginosa. The bacteria initially multiply in the protective mucus layer. Eventually, some of the bacteria reach the lung cells beneath the mucus layer and invade them. They primarily target the goblet cells, which are responsible for mucus production. Inside the cells, the bacteria multiply, causing the goblet cells to swell and eventually burst. This allows the infection to spread to adjacent cells.

The mini-lungs used in the study allow for the investigation of the infection directly in human cells. This is a significant advantage over so-called animal models, in which lung cells differ substantially from those of humans. With the lung model, various antibiotics can be tested to observe how the bacteria respond to treatment and where they might persist protected from antibiotics. Moreover, patient-specific cells can be used in these animal-free models, allowing individual differences between patients to be taken into account.