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Approche métabolomique pour l'étude de l'évolution adaptative de Pseudomonas aeruginosa au cours des infections pulmonaires chroniques dans la mucoviscidose

Oriane Moyne 1, 2
1 TIMC-TheREx [2016-2019] - Thérapeutique Recombinante Expérimentale [2016-2019]
TIMC - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
2 TIMC-EPSP [2016-2019] - Environnement et Prédiction de la Santé des Populations [2016-2019]
TIMC - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
Abstract : Chronic lung infection with Pseudomonas aeruginosa (P. a.) is considered as the leading cause of cysticfibrosis (CF) morbidity and mortality. During this persistent infection, the bacterium adapts to the typical lungenvironment of these patients and evolves within its host for decades. This adaptive evolution is driven byphenotypes, including a decrease in virulence and an increase in antibiotic resistance over time. Althoughseveral studies have attempted to elucidate the genetic mechanisms of this evolution, it remains difficulttoday to explain the relationships between the accumulated genomic mutations and the expression ofclinically 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-genomicobservation level: metabolomics. Metabolomics, the newest of the -omics disciplines, provides an instantview 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 patientswith CF. This bank was then clinically, phenotypically and metabolomically characterized. Integration ofthese different levels of information by multi-block statistical methods has allowed us to highlight metabolicpathways 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 ofimproving the management of these infections particularly resistant to antibiotics. In addition, our workdemonstrates the interest of metabolomics to study bacterial adaptive evolution under natural conditions.
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Oriane Moyne. Approche métabolomique pour l'étude de l'évolution adaptative de Pseudomonas aeruginosa au cours des infections pulmonaires chroniques dans la mucoviscidose. Pneumologie et système respiratoire. Université Grenoble Alpes, 2019. Français. ⟨NNT : 2019GREAS003⟩. ⟨tel-02402547⟩

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