Organoids revolutionize research on respiratory infections

Newswise — Biofilms are tough groups of bacteria that are very hard to treat when causing infections. Scientists have studied how biofilms form in labs, but we still don't know much about how they develop in the human respiratory tract.

Alexandre Persat and his team at EPFL made a significant breakthrough in solving this problem. They achieved this by creating organoids called AirGels. Organoids are small 3D tissues grown from stem cells that resemble real tissues and organs in the human body. AirGels represent a new approach in the field, allowing researchers to recreate and analyze the complex environments of organs in the lab. This advancement could provide valuable insights into understanding biofilm development in the human respiratory tract.

Tamara Rossy and her team have created the AirGels, which are engineered models of human lung tissue. These AirGels offer exciting new opportunities in infection research. They represent a major advancement in the field by closely mimicking the properties of the airway mucosa, such as mucus secretion and ciliary beating. With this technology, scientists can now investigate airway infections in a more lifelike and thorough manner, bridging the gap between laboratory studies and real-world clinical observations.

“There is a lot to say about this study, but the engineering of organoids for infection research has tremendous potential,” says Persat. “It’s a game changer.”

In their research, published in PLoS Biology, the scientists utilized AirGels to study how mucus influences the formation of biofilms by the antibiotic-resistant bacterium, Pseudomonas aeruginosa. They infected the AirGels with P. aeruginosa and observed the biofilm formation process in real time using advanced live microscopy with high resolution. This innovative approach allowed them to gain valuable insights into the dynamics of biofilm development in a realistic and controlled environment.

The researchers made a fascinating discovery during their observations: P. aeruginosa uses special retractile filaments called type IV pili (T4P) to actively induce the contraction of the host's mucus. These T4P filaments generate the forces needed to bring the airway's mucus together, enabling P. aeruginosa cells to gather and form a biofilm. To confirm their findings, the team conducted additional simulations and biophysical experiments on specific P. aeruginosa mutants, further validating their results. This study sheds light on the mechanisms behind biofilm formation by this antibiotic-resistant bacterium and provides new insights into potential targets for future treatments.

The study demonstrates that the AirGel organoid model offers valuable and distinctive insights into the mechanical interactions between bacteria and their host environments. In this particular case, it revealed a previously unknown mechanism employed by P. aeruginosa to contribute to biofilm formation in the respiratory tract. This breakthrough highlights the potential of AirGels in uncovering new aspects of infectious processes and how they occur in complex human tissues, which can significantly advance our understanding of infections and pave the way for innovative treatment strategies.

Creating organoids that accurately mimic the mucosal environment allows researchers to explore new possibilities in studying infections. They can now investigate how various factors like temperature, humidity, drugs, and chemical stress impact the infection's development and progression. Moreover, this advancement aids in developing specific treatments for antibiotic-resistant germs.