" A metabolomics approach to study within-host adaptation of Pseudomonas aeruginosa during cystic fibrosis chronic lung infections "
- Pr. Bertrand TOUSSAINT, PU-PH, Université Grenoble Alpes, CHU Grenoble-Alpes, Supervisor
- Dr. Dominique J. BICOUT, Chercheur, Université Grenoble Alpes, VetAgroSup Lyon, Co-supervisor
- Dr. Audrey LE GOUELLEC, MCU-PH, Université Grenoble Alpes, CHU Grenoble-Alpes, Co-advisor
- Pr. Max MAURIN, PU-PH, Université Grenoble Alpes, Laboratoire de Bactériologie, CHU Grenoble-Alpes, Co-advisor, guest
- Pr. Christophe PISON, Professeur des Universités - Praticien Hospitalier (PU-PH), Clinique de Pneumologie, CHU Grenoble-Alpes, President et Examiner
- Dr. Anne DOLEANS-JORDHEIM, Maître de Conférence Universitaire - Praticien Hospitalier (MCU-PH), Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Reporter
- Pr. Thierry JOUENNE, Directeur de Recherche, UMR CNRS 6270, Université de Rouen, Reporter
- Dr. Julien BOCCARD, Chercheur, Université de Genève (Suisse), Examiner
- Dr. Florence CASTELLI, Ingénieur-Chercheur, CEA Paris-Saclay, Examiner
Presentation video "Ma thèse au laboratoire TIMC" by Oriane Moyne for the Journée Des Doctorants 2018.
Chronic lung infection with Pseudomonas aeruginosa (P. a.) is considered as the leading cause of cystic fibrosis (CF) morbidity and mortality. During this persistent infection, the bacterium adapts to the typical lung environment of these patients and evolves within its host for decades. This adaptive evolution is driven by phenotypes, including a decrease in virulence and an increase in antibiotic resistance over time. Although several studies have attempted to elucidate the genetic mechanisms of this evolution, it remains difficult today to explain the relationships between the accumulated genomic mutations and the expression of clinically relevant phenotypes, or to correlate these mutations with the patient’s health status.
In this work, we propose to study the mechanisms underlying this adaptive evolution at a post-genomic observation level: metabolomics. Metabolomics, the newest of the -omics disciplines, provides an instant view of the metabolic activities, and furnishes a vision as close as possible to the phenotype. To this end, we constructed a bank of evolutive clonal P. a. lineages sampled during chronic lung infection in patients with CF. This bank was then clinically, phenotypically and metabolomically characterized. Integration of these different levels of information by multi-block statistical methods has allowed us to highlight metabolic pathways involved in within-host patho-adaptation of P. a. .
Our results rise new hypotheses for the development of therapeutic and diagnostic tools with the aim of improving the management of these infections particularly resistant to antibiotics. In addition, our work demonstrates the interest of metabolomics to study bacterial adaptive evolution under natural conditions.
Pseudomonas aeruginosa, adaptive evolution, metabolomics, multi-block analysis, cystic