Adding to current drugs a molecule, quorum sensing, reduces the production of certain harmful residues by bacteria and improves the effectiveness of existing treatments for cystic fibrosis, according to the researchers. results of a study published in the medical journal frontiers in Cellular and Infection Microbiology. This discovery would allow the development of new personalized therapies.
Cystic fibrosis is a fatal genetic disease that manifests as an overproduction of mucus in several organs, repeated bacterial infections, and progressive destruction of the lungs. There is no cure and when the disease has gained ground, the only solution is to have a lung transplant.
This disease is multiple and there are more than 2000 possible genetic mutations. Two treatments with limited efficacy are available for certain patients: Kalydeco for patients with a type of rare mutation (less than 4% of patients), and Orkambi for the most frequent mutation (79% of patients).
“People with cystic fibrosis have genetic defects that cause cells to produce a protein called CFTR abnormal and excess mucus in organs. Current drugs work to correct the defect in the CFTR protein. In an aseptic environment in vitro, the Kalydeco and Orkambi treatments work well. But in real life, the lungs of sick patients are colonized by bacteria, especially Pseudomonas aeruginosa. There was plenty of evidence that bacteria could interfere with treatment. Thanks to this study, we were able to determine which substances released by bacteria could interfere with the effectiveness of treatments, ”explains Professor Emmanuelle Brochiero.
Quorum sensing improves processing
Researchers at the University of Montreal Hospital Center Research Center in Canada collected nasal and lung cells removed from patients with cystic fibrosis at the time of lung transplantation. They then recreated respiratory epithelial tissue in the laboratory using tissue engineering to analyze the pathology and simulate therapeutic approaches.
Then, the scientists tested in vitro the impact of adding a Quorum Sensing inhibitor, from the furanone family. “We have shown that this molecule, by reducing the production of harmful residues by bacteria, preserves the effectiveness of treatments in the cells of patients with cystic fibrosis”, summarizes Emmanuelle Brochiero.
If the results of this study are conclusive, further research is needed to confirm the efficacy and safety of quorum sensing inhibitors that could potentially be used with current drugs.
“By using the cells collected from patients, we believe that it would be possible to test and predict the effectiveness of treatments such as Kalydeco and Orkambi, depending on the bacteria collected from each patient. We will also assess the ability of treatments to repair damaged lung tissue. And finally, it will be a question of identifying the most effective molecules, such as bacterial quorum sensing inhibitors, to counteract the harmful effect of infections. The ultimate goal is to improve treatments for patients and thus prolong their lives, ”concludes Emmanuelle Brochiero.
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