How do pathogens infiltrate the lungs? By utilizing human lung microtissues, a group of researchers has revealed the tactics utilized by a hazardous pathogen. The bacterium focuses on particular lung cells and has devised an intricate plan to penetrate the lung’s defensive barrier.
How do pathogens infiltrate the lungs? Using human lung microtissues, a team at the Biozentrum of the University of Basel has revealed the tactics utilized by a hazardous pathogen. The bacterium focuses on particular lung cells and has devised an intricate plan to penetrate the lung’s defensive barrier.
Earlier this year,The WHO has released a compilation of twelve of the most perilous bacterial pathogens in the world, which are resistant to various antibiotics and present a serious danger to human health. This compilation encompasses Pseudomonas aeruginosa, a highly feared hospital-acquired pathogen responsible for causing severe and life-threatening pneumonia. This pathogen poses a particularly serious threat to immunocompromised patients and individuals on mechanical ventilation, with mortality rates reaching as high as 50 percent.
Furthermore, Pseudomonas aeruginosa has developed a wide array of strategies to infiltrate the lungs and the body, as stated by research conducted by Prof. Urs.
Jenal and his team at the Biozentrum, University of Basel, have made new discoveries about the infection process by using lab-grown lung microtissues made from human stem cells. They published their findings in the scientific journal “Nature Microbiology,” detailing how the bacteria Pseudomonas is able to penetrate the top layer of lung tissue and invade deeper regions. This research was carried out as part of the National Center of Competence in Research (NCCR) “AntiResist.”
The thin layer of densely packed cells lining our lungs serves as a protective barrier for the deeper lung tissue. This surface is coated with mucus, which captures particles like microorganisms and is then removed from the air.
ays 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.”The bacteria target the goblet cells, which are a small part of the lung mucosa, breaching the defense line and causing the protective barrier to become leaky. The pathogens then rapidly spread into deeper tissue regions. This has led to the development of a new sensor for monitoring this process.bacterial infection
Scientists have used human lung organoids to understand how Pseudomonas bacteria infect the lungs. However, there is still uncertainty about how these pathogens change their behavior during the infection process. They need to be able to move around to spread over the tissue surface, then quickly stick to lung cells when they make contact, and later activate their virulence factors. It is known that the bacteria can quickly change their behavior using small signaling molecules. Until now, the technology to study these connections was not available.
Jenal’s team has now created a biosA new sensor has been developed to detect and monitor a small signaling molecule called c-di-GMP in individual bacteria. This breakthrough method was recently published in Nature Communications. According to Jenal, this advancement allows for the real-time monitoring and high-resolution tracking of how this signaling molecule is regulated during infection, as well as how it controls the virulence of the pathogen. Researchers now have a detailed understanding of when and where individual bacterial cells activate specific programs to regulate their behavior. This new method also allows for more in-depth investigations into lung infections.
Organ models replicate conditions found in patients
“T”Thanks to the advancement of human lung organoids, we have gained a deeper insight into the behavior of pathogens in human tissue and potentially in patients,” Jenal emphasizes. “This brings us significantly closer to achieving the goal of NCCR AntiResist.” Organoids of the human lung and other organs, such as the bladder, enable researchers to analyze the impact of antibiotics on tissue, such as pinpointing where and how bacteria endure treatment. These organ models will be essential in the future for creating innovative and successful approaches to combat pathogens.”
