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Friday, 01/20/2023
Researchers from IAMR group publish in Nature Biotechnology a ‘Living medicine’ created to tackle drug-resistant lung infections.
Researchers from IAMR group publish in Nature Biotechnology a ‘Living medicine’ created to tackle drug-resistant lung infections.
This excellent result comes from a collaborative consortium in which our IDIBAPS-Ciberes group added an important translational value on this new promising technology developed by CRG, also with the collaboration of Institute of Agrobiotechnology (IdAB), a joint research institute of Spain’s CSIC and the government of Navarre. https://www.nature.com/articles/s41587-022-01584-9#citeas.
Researchers have designed the first ‘living medicine’ to treat lung infections. The treatment targets Pseudomonas aeruginosa, a type of bacteria which is naturally resistant to many types of antibiotics and is a common source of infections in hospitals.
The treatment involves using a modified version of the bacterium Mycoplasma pneumoniae, removing its ability to cause disease and repurposing it to attack P. aeruginosa instead. The modified bacterium is used in combination with low doses of antibiotics that would otherwise not work on their own.
Researchers tested the efficacy of the treatment in mice, finding that it significantly reduced lung infections. The ‘living medicine’ doubled mouse survival rate compared to not using any treatment. Administering a single, high dose of the treatment showed no signs of toxicity in the lungs. Once the treatment had finished its course, the innate immune system cleared the modified bacteria in a period of four days.
The findings are published in the journal Nature Biotechnology and are supported by the “la Caixa” Foundation through the CaixaResearch Health call. The study was led by researchers at the Centre for Genomic Regulation (CRG) and Pulmobiotics in collaboration with the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona and the Institute of Agrobiotechnology (IdAB), a joint research institute of Spain’s CSIC and the government of Navarre.
P. aeruginosa infections are difficult to treat because the bacteria lives in communities that form biofilms. Biofilms can attach themselves to various surfaces in the body, forming impenetrable structures that escape the reach of antibiotics. “Our group has outstanding experience in the field of ventilator associated pneumonia (VAP)” says Prof. Antoni Torres, group leader of IAMR-IDIBAPS and Ciberes research group. “In addition, we have a consolidated animal model of VAP, coordinated by Dr. Ana Motos, that has been very productive and has attracted industries from all over the world to test their technology” he adds.
“This model allows us to study real in vivo biofilm adding an important translational value to all the preventive and treatment strategies tested in our model” says Dr. Laia Fernández-Barat, who first described in vivo biofilm in the endotracheal tubes of this animal model and afterwards she translated their findings to ICU patients. “Endotracheal tubes are usually discarded at patient’s extubation but we keep them in a collection since it is a valuable sample to study biofilms” she adds.
P. aeruginosa biofilms can grow on the surface of endotracheal tubes of orotracheally intubated critically-ill patients who require mechanical ventilators to breathe. This, has been is one of the factors associated to ventilator-associated pneumonia (VAP), a condition which affects one in four (9-27%) patients who require intubation and complicates patients’ outcomes.
The authors of the study engineered M. pneumoniae to dissolve biofilms by equipping it with the ability to produce various molecules including pyocins, toxins naturally produced by bacteria to kill or inhibit the growth Pseudomonas bacterial strains. To test its efficacy, they collected P. aeruginosa biofilms from the endotracheal tubes of patients in intensive care units. They found the treatment penetrated the barrier and successfully dissolved the biofilms.
“We have developed a battering ram that lays siege to antibiotic-resistant bacteria. The treatment punches holes in their cell walls, providing crucial entry points for antibiotics to invade and clear infections at their source. We believe this is a promising new strategy to address the leading cause of mortality in hospitals,” says Dr. María Lluch, Chief Scientific Officer at Pulmobiotics, co-corresponding author of the study and principal investigator at the International University of Catalonia.
With the aim of using the ‘living medicine’ to treat VAP, the researchers will carry out further tests before reaching the clinical trial phase. The treatment is expected to be administered using a nebulizer, a device that turns liquid medicine into a mist which is then inhaled through a mouthpiece or a mask.
M. pneumoniae is one of the smallest known species of bacteria. Dr. Luis Serrano, Director of the CRG, first had the idea to modify the bacteria and use it as a ‘living medicine’ two decades ago. Dr. Serrano is a specialist in synthetic biology, a field that involves repurposing organisms and engineering them to have new, useful abilities. With just 684 genes and no cell wall, the relative simplicity of M. pneumoniae makes it ideal for engineering biology for specific applications.
Cite this article: Mazzolini R, Rodríguez-Arce I, Fernández-Barat L, Piñero-Lambea C, Garrido V, Rebollada-Merino A, Motos A, Torres A, Grilló MJ, Serrano L, Lluch-Senar M. Title: Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms. Nat Biotechnol. 2023 Jan 19. doi: 10.1038/s41587-022-01584-9. Epub ahead of print. PMID: 36658340.
Related links
- https://www.clinicbarcelona.org/en/news/living-medicine-created-to-tackle-drug-resistant-lung-infections
- https://www.clinicbarcelona.org/noticias/crean-una-pildora-viva-para-combatir-las-infecciones-pulmonares-resistentes-a-los-antibioticos
- https://www.clinicbarcelona.org/ca/noticies/creen-una-pindola-viva-per-a-combatre-les-infeccions-pulmonars-resistents-als-antibiotics