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I2SysBio enables a cystic fibrosis patient to overcome acute rejection of her lung transplant with phage therapy

Written by admin | 17/09/2025

A team led by the Institute of Integrative Systems Biology (I2SysBio), a research center at PCUV, has successfully eradicated chronic Pseudomonas aeruginosa infection in a cystic fibrosis (CF) patient with double lung transplantation. Compassionate use therapy with bacteriophages, still under clinical development, has shown its potential as a complementary treatment in cases of antibiotic-resistant infections. The study has been published by the American Society for Microbiology

Resistance to antimicrobial drugs, such as antibiotics, poses a significant threat to human health worldwide. The search for alternative treatments is therefore a focus of scientific research in fields ranging from biological therapies and new molecules to nanotechnology, microbiome or gene editing.

Phages or bacteriophages, viruses that infect and destroy specific bacteria, are being used as a complementary treatment in multidrug-resistant infections that do not respond to traditional therapies. Although not yet approved as conventional medicinal products, their application may take place under compassionate use regimens or in clinical trials, limited to situations where no viable alternatives exist.

The article recently published by ASM Case Reports describes the use of phage therapy to treat chronic infection with Pseudomonas aeruginosa, a bacterium that causes infections with high morbidity and mortality, and most likely the most invasive pathogen in bronchopulmonary infections due to cystic fibrosis (CF). This genetic disorder, which mainly affects the lungs and intestines, has a prevalence in Europe of 1/5,000 people.

"Although this therapy still faces regulatory and clinical challenges, the advances in this field are encouraging and point to its future integration into conventional medicine," said Pilar Domingo, I2SysBio researcher and principal investigator of the project

The work team, led by the virologist and researcher of the Institute of Integrative Systems Biology (I2SysBio), located in the scientific-academic area of the University of Valencia Science Park (PCUV), Pilar Domingo-Calap, has successfully eradicated chronic Pseudomonas aeruginosa infection in a 44-year-old cystic fibrosis (CF) patient who underwent two bilateral lung transplants. In addition, the work has been supported by the spin-off of the University of Valencia Evolving Therapeutics, which is located in the business area of PCUV and of which Pilar Domingo is scientific director. 

The patient had been suffering from chronic lung infection since childhood and had undergone two bilateral lung transplants at age 29 and 40, both of which were followed by episodes of rejection and therapeutic attempts with intravenous antibiotics that proved ineffective, worsening your lung function and overall condition. At the end of 2023, the Spanish Agency for Medicines and Health Products (AEMPS) approved the compassionate treatment and authorized the Institute of Integrative Systems Biology to carry it out under the direction of Pilar Domingo, principal investigator of the project.

The treatment consisted of the supply of foggy phages in two 10-day batches, combined with the conventional treatment of the patient, whose lung capacity improved within a few days until the infection was completely eradicated, thus avoiding a third transplant. "The patient is currently with a good quality of life and the bacteria has not reappeared since treatment with phages, already more than a year and a half ago, demonstrating the long-term effectiveness of the therapy," adds the researcher.

"The patient is currently with a good quality of life and the bacteria has not reappeared since treatment with phages, already more than a year and a half ago, demonstrating the long-term effectiveness of therapy", Pilar Domingo, I2SysBio researcher and lead project investigator

This case, which pioneered the application of bacteriophages in transplanted patients, highlights the enormous potential of phagotherapy as a complementary treatment for chronic and resistant infections. "Although this therapy still faces regulatory and clinical challenges, advances in this field are encouraging and point to its future integration into conventional medicine," concludes Pilar Domingo-Calap.

The project has been financed through crowdfunding in collaboration with the Spanish Federation of Cystic Fibrosis, Project SEJIGENT/2021/014 (Council of Innovation, Universities, Science and Digital Society; Generalitat Valenciana), Project PID2020-112835RA-I00 (Ministry of Science, Innovation and Universities), and the contract Ramón y Cajal RYC2019-028015-I (Ministry of Research and Innovation). The study also involved Yale University (USA) and the Puerta de Hierro University Hospital in Madrid.

About Pilar Domingo-Calap

Pilar Domingo-Calap is a biologist, PhD with an extraordinary award from the University of Valencia (2012), and researcher Ramón y Cajal at the Institute of Integrative Systems Biology (I2SysBio). Since December 2020 he leads the group of Environmental and Biomedical Virology, whose main focus is to explore environmental virology with biomedical applications, especially the use of bacteriophages to combat multidrug-resistant bacteria. During his training he completed his thesis with stays at the CNRS (France) and at INSERM (Strasbourg), deepening in biomedicine, mutation and viral immunity.

His scientific career is highlighted by more than 70 publications in high-impact journals such as Nature Communications, Nature Microbiology, PLOS Genetics, Cell Reports or Med. In addition, she has reviewed over a hundred articles and is an associate editor for journals such as Microbiology Spectrum, Frontiers in Virology and BioDesign Research.

As co-founder and scientific director of the spin-off Evolving Therapeutics, Pilar has been key to moving from research to real solutions: developing personalized phage-based therapies to treat multi-resistant bacteria in human, animal and plant health. He has coordinated compassionate treatments for patients with chronic infections that are difficult to treat and led the first pilot trial in agriculture against Xylella fastidiosa in the Balearic Islands, preserving the microbiota of the treated organism. In 2025 she was awarded the Women TechEU prize, which is endowed with € 75,000 plus mentoring, to expand her company’s laboratories. 

Source: UV News