How dangerous hospital germs infect the lungs

The hospital bacterium Pseudomonas aeruginosa causes life-threatening pneumonia. Swiss researchers have now discovered how bacteria manage to overcome lung defences.

The team cultured lung organoids (3D cultures of stem cells that mimic the cellular complexity and function of human organs) and then observed the sophisticated strategy the pathogen uses to penetrate the lung's defense line. The results were published in the specialized journal “Natural Microbiology” published.

Mucous barrier against pathogens

The entire respiratory system is lined with a specialized mucous membrane that protects the deeper layers of lung tissue. The mucous membrane consists of millions of moving hair cells, namely cilia, between which are located mucus-producing goblet cells.

Its mucus prevents microorganisms and thus pathogens from penetrating deep into the lungs. But they form an almost impenetrable barrier. Of all things Pseudomonas aeruginosa However, he is able to break through this barrier.

Infection is one of the most common causes of pneumonia

These bacteria are hospital germs and, according to the Robert Koch Institute (RKI) in Berlin, are among the most common causes of pneumonia occurring during a hospital stay and are particularly life-threatening for immunocompromised patients who are on mechanical ventilation.

The World Health Organization (WHO) has listed Pseudomonas aeruginosa as one of the world's twelve most dangerous bacterial pathogens that is resistant to multiple antibiotics.

How pathogens overcome the mucus barrier

But how does the pathogen penetrate the mucous barrier? Evidence is provided by lung organoids created by a Swiss researcher, which were obtained from human stem cells and infected with the pathogen.

“We have grown human lung microtissues that realistically mimic the infection process in the patient’s body,” explains Urs Ginal from the Biozentrum at the University of Basel. “These lung models allowed us to reveal the infection strategy of the pathogen.”

Advanced infection strategy

In fact, the bacteria used a sophisticated strategy to penetrate barrier tissue. This is what the study says:

• The first stage of infection: “In the initial stage of infection, Pseudomonas aeruginosa spreads rapidly using nutrients available in the mucus layer.” In this initial stage, only a few bacteria come into contact with the tissue surface and the tissue remains healthy.
• The second stage of infection: “In the next stage of the infection process, Pseudomonas aeruginosa begins to attach to and attack the underlying epithelial tissue, possibly due to mucus depletion, as evidenced by cessation of pathogen growth.”
• The third stage of infection: The bacteria then use the mucus-producing goblet cells as a Trojan horse. “By attacking goblet cells, which make up only a small part of the lung lining, bacteria can penetrate the defense line and open the gate,” says Genal.

Pathogens settle in weak spots in the immune system

Scientists explained that the pathogens attacked the goblet cells with concentrated force, invaded them, multiplied, and ultimately caused the cells to explode and thus die.

The explosion of dead cells, in turn, causes cracks in the barrier and thus leaks, which bacteria immediately exploit: they quickly settle in weak points, and from there they spread to deeper tissue areas.

More effective strategies in combating pathogens

“Thanks to the development of human lung organoids, we now understand much better how pathogens behave in human tissues, and perhaps also in patients,” says Genal, summarizing the research results.

Organoids taken from human lungs and other organs such as the bladder have allowed researchers to study the effects of antibiotics in tissues, for example determining where and how bacteria survive during treatment. They are therefore indispensable for developing new and effective strategies to combat pathogens in the future.