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Lung Organoids Reveal How Pathogens Invade Human Lung Tissue

The pathogenic bacterium Pseudomonas aeruginosa breaching through the respiratory epithelia of a human lung microtissue model, captured via Scanning Electron Microscopy.
Credit: Benoit Laventie, Biozentrum, University of Basel.
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Earlier this year, the WHO published a list of twelve of the world’s most dangerous bacterial pathogens that are resistant to multiple antibiotics and pose a grave threat to human health. This list includes Pseudomonas aeruginosa, a much-feared nosocomial pathogen that causes severe and life-threatening pneumonia. This pathogen is especially threatening to immunocompromised patients and those on mechanical ventilation, with mortality rates up to 50 percent.

The lung barrier is penetrable

Pseudomonas aeruginosa has developed a broad range of strategies to invade the lungs and the body. Researchers led by Prof. Urs Jenal at the Biozentrum, University of Basel, have now gained novel insights into the infection process using lab-grown lung microtissues generated from human stem cells. In the scientific journal Nature Microbiology, they describe how Pseudomonas breaches the top layer of lung tissue and invades deeper areas. This study was conducted as part of the National Center of Competence in Research (NCCR) “AntiResist”.

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Our lungs are lined by a thin layer of tightly packed cells that protects the deeper layers of lung tissue. The surface is covered with mucus, which traps particles such as microorganisms and is removed from the airways by specialized cells. This layer serves as an effective almost impenetrable barrier against invading pathogens. However, Pseudomonas bacteria have found a way to breach it. But how the pathogen crosses the tissue barrier has remained a mystery until now.

Lung organoids provide new insight into infections in humans    

“We have grown human lung microtissues that realistically mimic the infection process inside a patient’s body,” explains Jenal. “These lung models enabled us to uncover the pathogen’s infection strategy. It uses the mucus-producing goblet cells as Trojan horses to invade and cross the barrier tissue. By targeting the goblet cells, which make up only a small part of the lung mucosa, the bacteria can breach the defense line and open the gate.”