'Living medicine' tackles drug-resistant biofilms growing on ventilation tubes
· Medical Xpressby Center for Genomic Regulation
edited by Sadie Harley, reviewed by Robert Egan
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A "living medicine" has thinned biofilms of antibiotic-resistant Pseudomonas aeruginosa in the lungs of pigs, according to the findings of a study published in the journal eBioMedicine. The experimental treatment involves inhaling a genetically modified bacterium designed to target layers of drug-resistant Pseudomonas aeruginosa that grow on the surfaces of endotracheal tubes used in hospitals.
It's the first time the experimental treatment, which has previously only been shown to tackle biofilms in mice, has also worked in pigs, a large animal with lungs that are similar in size, structure and immune response to human lungs.
It's also the first time the treatment has been shown to be administrable through a nebulizer, the same type of medical device human patients would use. Breathing in the "living medicine" thinned the biofilm inside breathing tubes from 6.08 to 3.67 micrometers, reducing thickness by around 40%.
A lung bacterium reprogrammed to target biofilms
The treatment involves Mycoplasma pneumoniae, a bacterium which normally causes a mild lung infection but, through genetic engineering, has been repurposed to be harmless for humans. The engineered bacterium was loaded with genes that dissolve sugars holding a biofilm together, as well as toxins that specifically only target Pseudomonas aeruginosa.
"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," explains Dr. Irene Rodríguez-Arce, senior co-author of the study.
When the researchers examined the lungs afterward, they found no signs of damage caused by the engineered bacterium. The treatment also showed no measurable effect on the animals' own airway bacteria, suggesting the living medicine targets Pseudomonas specifically.
Breathing tubes shelter antibiotic-resistant bacteria
The study could one day help patients who cannot breathe for themselves in the hospital. They are usually kept alive by passing a tube into the windpipe. Within days, bacteria colonize the inside of that tube and form a slimy, protective layer called a biofilm.
Antibiotics given through a drip struggle to penetrate the physical barrier of biofilms, causing recurring infections. In intubated patients, this is a known cause of ventilator-associated pneumonia (VAP). Around 1 in 4 cases are caused by Pseudomonas aeruginosa, which is frequently resistant to several types of antibiotics.
"Antibiotic resistance is a silent pandemic we see affecting intubated patients every day and Pseudomonas aeruginosa is among the hardest infections to clear. Our work represents a different line of attack, and one we badly need," says Dr. Antoni Torres, senior co-author of the study.
Toward a first human safety trial
The authors say their findings support a future first-in-human safety trial. Combining the "living medicine" with intravenous antibiotics or making further tweaks to the molecules that dissolve biofilms could further improve the experimental treatment's effectiveness.
"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. The research team at the CRG is also creating versions of the living medicine that can tackle pulmonary fibrosis and lung cancer.
The study is a collaboration between the Center for Genomic Regulation (CRG) and Hospital Clínic-IDIBAPS, both in Barcelona, with the animal studies carried out at the University of Barcelona. It was led by co-first authors Laia Fernández-Barat and Ana Motos, with Torres, Serrano and Rodríguez-Arce as senior authors.
Publication details
eBioMedicine (2026). DOI: 10.1016/j.ebiom.2026.106537
Journal information: EBioMedicine
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Pulmonary medicineInfectious diseases Provided by Center for Genomic Regulation Who's behind this story?
Sadie Harley
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