Inhaled Therapy Uses Modified Bacteria to Break Down Pseudomonas Biofilms

Biofilms are protective layers of bacteria that can form inside endotracheal tubes during mechanical ventilation, making infections difficult to treat because intravenous antibiotics often struggle to penetrate them. These biofilms can contribute to ventilator-associated pneumonia, with approximately one in four cases caused by Pseudomonas aeruginosa. To address this challenge, researchers have developed an inhaled “living medicine” designed to target drug-resistant Pseudomonas biofilms in ventilation tubes.

Researchers at the Center for Genomic Regulation (CRG) and Hospital Clínic-IDIBAPS in Barcelona developed an experimental inhaled treatment using genetically engineered Mycoplasma pneumoniae, a bacterium normally associated with respiratory infections. The bacterium was modified to make it harmless to humans and reprogrammed to produce molecules that break down the sugars holding bacterial biofilms together, along with toxins that specifically target Pseudomonas aeruginosa.

The approach was evaluated in pigs, whose lungs share similarities with human lungs in size, structure, and immune response. Building on earlier studies demonstrating activity against biofilms in mice, researchers tested whether the engineered bacteria could remain effective in a larger animal model. The treatment was delivered through a nebulizer, a device commonly used to administer inhaled medications.

Following inhalation, the treatment reduced biofilm thickness inside breathing tubes by approximately 40%, from 6.08 to 3.67 micrometers. Examination of lung tissue revealed no signs of damage associated with the engineered bacteria, while the animals’ normal airway microbiota remained largely unaffected. These findings suggest that the treatment can selectively target Pseudomonas biofilms without significantly disrupting surrounding respiratory bacteria.

The findings were published in eBioMedicine on November 11, 2026, with animal studies conducted at the University of Barcelona as part of the collaboration between CRG and Hospital Clínic-IDIBAPS. The results support further development toward a first-in-human safety trial. Researchers also suggest that combining the treatment with intravenous antibiotics or refining its biofilm-dissolving molecules could further improve its effectiveness.

“Our study is part of an emerging field of medicine known as live biotherapeutics. In this case we've taken a bacterium naturally adapted to the lung and reprogrammed it so that it delivers therapeutic molecules instead of causing damage. It's a Trojan horse strategy against disease,” said Dr. Irene Rodríguez-Arce, senior co-author of the study.

"I am confident that with modifications to the bacterial chassis' payload, we could completely dissolve the biofilms on the surface of endotracheal tubes and clear P. aeruginosa infections entirely," explains ICREA research professor Luis Serrano, senior co-author of the study. 

Related Links
Center for Genomic Regulation
Hospital Clínic-IDIBAPS