“Therapeutic strategies alternative to antibiotics are of great interest, especially in the current context of growing concern about antimicrobial resistance,” notes Laia Fernàndez-Barat, researcher at IDIBAPS, CIBERES member and author of the article.
Antibiotic resistance: the silent pandemic of intensive care units
One of the most common and deadly infections detected in intensive care units is bacterial biofilms, which grow inside the endotracheal tubes of intubated patients and form a viscous protective layer. This is a known cause of ventilator-associated pneumonia, and approximately one in four cases are caused by Pseudomonas aeruginosa, a bacterium that is often resistant to several types of antibiotics. Moreover, the antibiotics administered via drip struggle to penetrate the physical barrier of biofilms, causing recurrent infections.
“Antibiotic resistance is a silent pandemic that we see affecting intubated patients every day, and Pseudomonas aeruginosa is one of the most difficult infections to eliminate. Our work represents a different line of attack, and one that we urgently need,” explains Antoni Torres, of the IDIBAPS Mechanisms of lung injury: from infection and critical illness to fibrosis group and co-lead author of the study.
“Living medicine” to combat Pseudomonas aeruginosa
In this study, they tested an experimental treatment consisting of a genetically modified bacterium, designed to attack drug-resistant P. aeruginosa biofilms.
This was the first time that this experimental treatment, which had previously only been shown to be effective in mice, had been tested in large animals with lungs similar in size, structure and immune response to human beings. Furthermore, for the first time, its effectiveness was tested via inhalation using a nebuliser.
The treatment used Mycoplasma pneumoniae, a bacterium that normally causes a mild lung infection but was re-engineered to be harmless to humans. The modified bacterium was also loaded with genes that dissolve the sugars that hold a biofilm together, as well as with toxins that only affect Peudomonas aeruginosa.
“Our modified bacterium releases enzymes that essentially dissolve the Pseudomonas mucus that coats the endotracheal tube. It is an extraordinary pheromone visible under an electron microscope”, explains Irene Rodríguez-Arce, a researcher at the Centre for Genomic Regulation (CRG) and co-author of the study.
Reduction of almost 40% in endotracheal tube biofilms
The experimental treatment, or “living medicine”, reduced the bacterial film inside the endotracheal tubes from 6.08 to 3.67 micrometres, showing promising results for combating ventilator-associated pneumonia.
Additionally, upon examining the lungs, there were no signs of damage caused by the modified bacterium. The treatment also showed no measurable effect on the bacteria in the animals’ airways, suggesting that the living medicine specifically targets Pseudomonas without affecting other microorganisms.
The authors say that their findings support a future human safety trial and plan to carry out further research. The next step is to test the modified bacterium alongside intravenous antibiotics to see if they can enhance treatment effectiveness.
Study of reference
Fernández-Barat L, Motos A, Segura-Morales C et al. Targeting Pseudomonas aeruginosa ventilator-associated pneumonia with a non-antibiotic and biofilm-disrupting live biotherapeutic: preclinical safety and efficacy study. eBioMedicine, 2026; 134
