Bioinformatics to the aid of cystic fibrosis patients

2024-10-05 04:00:00

This text is part of the special notebook Innovating for better care

A recent study, conducted among others by the Institute of Integrative and Systems Biology at Laval University, revealed the existence of pathogenic clones adapted to the lungs of people with cystic fibrosis. A valuable discovery that was made possible thanks to technological innovations in sequencing.

For years, Roger Levesque has been carefully studying the blue pus bacillus (Pseudomonas aeruginosa). Over time, the professor at the Faculty of Medicine and researcher at the Institute of Integrative and Systems Biology at Laval University has built up a vast microbial database. He thus collected strains taken from patients, animals or from the ground, rivers and lakes. But it was only recently that he was able to sequence these genomes, in close collaboration with experts from the universities of Cambridge and Oxford. Work which led to an important discovery.

Resistant clones

Published in the journal Science, this work shed light on how the blue pus bacillus, a harmless bacteria in a natural environment, generated pathogenic clones intended to colonize the lungs of patients with cystic fibrosis. “These clones have developed characteristics that allow them to survive inside the macrophages, the pulmonary immune cells, which normally destroy them,” explains Roger Levesque. These are strains that are not found in people who suffer from other types of infections of the skin or eyes, for example. »

This revelation comes at a crucial time, when the World Health Organization (WHO) has once again placed Pseudomonas aeruginosa on the list of pathogens to be monitored very closely in 2024. Like other bacteria, the blue pus bacillus has attracted the attention of the WHO for its worrying resistance to antibiotics. However, the search for new treatments requires improving knowledge of these bacteria with their formidable adaptability and which represent a great threat to human health.

As such, the study in which Roger Levesque and his colleagues from the Institute of Integrative and Systems Biology at Laval University, Irena Kukavica-Ibrulj and Jeff Gauthier participated, undoubtedly constitutes a remarkable advance . “This will allow us to monitor pathogenic clones in cystic fibrosis patients much more precisely with markers that we are currently developing,” emphasizes Mr. Levesque. This will help us find how we can intervene with antibiotic therapy by targeting exactly these strains, without having to take into account the whole range of strains that we can see everywhere. »

New perspectives

This promising breakthrough would not have been possible without the significant advances made in bioinformatics in recent years. “It’s remarkable what we can do today in terms of analyzing infectious diseases. We have come so far that we can sequence the genome of an infected human cell, such as a macrophage. We have incredible tools that we didn’t have even five years ago,” says Roger Levesque. His laboratory was able to develop high-level work in genomics thanks to financial support from Genome Canada and Génome Québec.

As technology has evolved, research costs have also decreased significantly. “The genome of the first strain of Pseudomonas aeruginosa was sequenced in 2000 for the sum of 5 million dollars. Today, we can do this same sequencing for around $50 in my laboratory, testifies Roger Levesque. Furthermore, the quality of sequencing is now much higher. We can see point mutations in microbial genes, which we couldn’t do before. »

Carried out in collaboration with Julian Parkhill, a recognized bioinformatics expert from the University of Cambridge, the work carried out on the bacterium Pseudomonas aeruginosa provides new perspectives. And not just regarding the search for effective treatments. “We used technology and a methodology that can be used for other infections of microorganisms. This paves the way for more important studies to better understand how a bacteria that is non-pathogenic in the environment can evolve to cause disease in humans and animals,” concludes Roger Levesque.

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