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Basel, Switzerland — A groundbreaking study published on Monday has revealed novel insights into how pathogens invade the lungs, utilizing lab-grown lung microtissues generated from human stem cells. Conducted by researchers at the Biozentrum of the University of Basel, the study focuses on the dangerous bacterium Pseudomonas aeruginosa, which is part of the World Health Organization’s list of 12 most dangerous bacterial pathogens.
Pseudomonas aeruginosa poses a significant threat, particularly to immunocompromised patients and those on mechanical ventilation, where mortality rates can reach up to 50 percent. The study, published in the journal Nature Microbiology, sheds light on the bacterium’s sophisticated strategy to breach the lungs’ defenses.
The research team, led by Prof. Urs Jenal, discovered that Pseudomonas aeruginosa targets specific lung cells, employing a clever method to penetrate the lung tissue’s protective barriers. Using lab-grown human lung microtissues that closely mimic the infection process within a patient’s body, the scientists were able to closely observe the bacterium’s tactics.
“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,” explained Prof. Jenal.
The bacterium attacks and invades the goblet cells using specialized secretion systems, replicates inside these cells, and eventually kills them. The death of these cells results in ruptures in the tissue layer, compromising the protective barrier and allowing the pathogens to rapidly colonize and spread into deeper tissue regions.
In addition to uncovering these invasion mechanisms, Jenal’s team developed a biosensor capable of measuring and tracking a small signaling molecule called c-di-GMP in individual bacteria in real-time. This innovative tool provides further insight into the bacterial infection process and could lead to new strategies for combating such infections.
The findings from this study offer crucial information that could aid in developing new treatments and preventive measures against Pseudomonas aeruginosa and similar pathogens, potentially saving countless lives in vulnerable patient populations.
