Pathogenic clones finely adapted to the lungs of people with cystic fibrosis

Pathogenic clones finely adapted to the lungs of people with cystic fibrosis
Pathogenic clones finely adapted to the lungs of people with cystic fibrosis

In 2024, the World Health Organization once again placed the bacteria Pseudomonas aeruginosa on its short list of priority pathogens. This list includes the names of bacteria for which the WHO considers that it is urgent to advance knowledge because these microorganisms resistant to several antibiotics are wreaking havoc throughout the world. In this regard, P. aeruginosa does not give up its place: in 2019, it caused 560,000 deaths on the planet.

A study published on July 4 in the journal Science by an international team, including three researchers from Laval University, responds to this call from the WHO. The researchers present the results of work that shows how P. aeruginosaa bacteria that is harmless in natural environments, has evolved to give rise to clones adapted to a very special ecological niche: the lungs of people suffering from cystic fibrosis.

The team from Cambridge, Oxford and Laval University analyzed 9,829 strains of P. aeruginosa collected in natural environments, from animals and from humans, in around fifty countries between 1900 and 2018. Of these, 9,573 samples came from 2,765 patients with an infection caused by P. aeruginosa.

“We found that 51% of infections caused by P. aeruginosa “The number of clones worldwide was attributable to 21 major clones,” says one of the study’s authors, Roger Levesque, professor at the Faculty of Medicine and researcher at the Institute of Integrative and Systems Biology at Laval University.

Subsequent analyses produced a clear conclusion. “There are two major divisions among the pathogenic clones of P. aeruginosasummarizes Professor Levesque. The first group is found in people with cystic fibrosis while the second group is found in patients who do not have this disease. These preferences are associated with the expression or non-expression of certain genes.”

One of the differences observed between the two groups helps to understand why P. aeruginosa causes chronic respiratory infections in people with cystic fibrosis. “We found that the expression of certain genes allowed clones from the cystic fibrosis group to survive inside lung immune cells – macrophages – that normally destroy them,” says Professor Levesque. “This example shows how these clones have developed adaptations that ensure their survival in the lungs of people with cystic fibrosis.”

Cystic fibrosis is the leading cause of death among children and young adults in Canada. Approximately 4,300 Canadians are living with this incurable disease. Previous studies have shown that the severity of cystic fibrosis is directly related to the severity of infections caused by P. aeruginosa.

“In young people and adults, treatment of this disease mainly consists of controlling this bacteria using antibiotics,” says Professor Levesque. “The fact that it has become resistant to several antibiotics is therefore a major concern. The results of our study, particularly those affecting macrophages and genes involved in infection mechanisms, suggest new treatment options.”

Irena Kukavica-Ibrulj and Jeff Gauthier, from the Institute of Integrative and Systems Biology at Laval University, are also among the list of signatories of the study published in Science.

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