Biofilms are highly resistant communities of bacteria that pose a major challenge in the treatment of infections. Pseudomonas aeruginosa is a notorious biofilm former that causes antibiotic–recalcitrant pneumonia in the respiratory tract. While studying biofilm formation in laboratory conditions has been extensively conducted, understanding their development in the complex environment of the human respiratory tract has remained elusive.

To investigate the process of biofilm formation in more realistic conditions, researchers have developed AirGels—3D, optically accessible tissue–engineered human lung models that emulate the physiological properties of the airway mucosa, including mucus secretion and ciliary beating. This technology allows scientists to study airway infections in a more realistic and comprehensive manner, bridging the gap between in vitro studies and clinical observations. By infecting AirGels with P. aeruginosa, and studying them under high-resolution live microscopy, the team was able to observe the bacterium form biofilms in real-time.

The research is published in PLoS Biology, in the paper, “Pseudomonas aeruginosa type IV pili actively induce mucus contraction to form biofilms in tissue-engineered human airways.

“There is a lot to say about this study, but the engineering of organoids for infection research has tremendous potential,” said Alexandre Persat, PhD, assistant professor at EPFL. “It’s a game changer.”

In the study, the researchers used AirGels to investigate the role of mucus in the process of biofilm formation by P. aeruginosa. They found that Paeruginosa “forms mucus–associated biofilms within hours by contracting luminal mucus early during colonization. Mucus contractions facilitate aggregation, thereby nucleating biofilms.”

In addition, their observations revealed that P. aeruginosa actively induces contraction of its host’s mucus using the retractile filaments, type IV pili (T4P). The T4P filaments generate the necessary forces to contract the airway’s mucus, which allows P. aeruginosa cells to aggregate and form a biofilm. The researchers validated their findings with follow-up simulations and biophysical experiments on selected P. aeruginosa mutants.

The study shows that the AirGel organoid model can provide unique insights into the mechanical interactions between bacteria and their hosts’ environments, in this case uncovering a previously unknown mechanism that contributes to biofilm formation in the respiratory tract.

Being able to engineer organoids that faithfully replicate the mucosal environment opens up new avenues of exploration, enabling researchers to uncover overlooked aspects of infections, investigating the influence of additional physiological factors, such as temperature, humidity, drugs, and chemical stressors on the development and progression of infection, and develop targeted treatments against antibiotic-resistant pathogens.

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