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Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections
by
Oriane Moyne, Florence Castelli, Dominique J. Bicout, Julien Boccard, Boubou Camara, Benoit Cournoyer, Eric Faudry, Samuel Terrier, Dalil Hannani, Sarah Huot-Marchand, Claire Léger, Max Maurin, Tuan-Dung Ngo, Caroline Plazy, Robert A. Quinn, Ina Attree, François Fenaille, Bertrand Toussaint and Audrey Le Gouëllec
Cited by 21 | Viewed by 4918
Abstract
Pseudomonas aeruginosa (
P.a) is one of the most critical antibiotic resistant bacteria in the world and is the most prevalent pathogen in cystic fibrosis (CF), causing chronic lung infections that are considered one of the major causes of mortality in CF
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Pseudomonas aeruginosa (
P.a) is one of the most critical antibiotic resistant bacteria in the world and is the most prevalent pathogen in cystic fibrosis (CF), causing chronic lung infections that are considered one of the major causes of mortality in CF patients. Although several studies have contributed to understanding
P.a within-host adaptive evolution at a genomic level, it is still difficult to establish direct relationships between the observed mutations, expression of clinically relevant phenotypes, and clinical outcomes. Here, we performed a comparative untargeted LC/HRMS-based metabolomics analysis of sequential isolates from chronically infected CF patients to obtain a functional view of
P.a adaptation. Metabolic profiles were integrated with expression of bacterial phenotypes and clinical measurements following multiscale analysis methods. Our results highlighted significant associations between
P.a “metabotypes”, expression of antibiotic resistance and virulence phenotypes, and frequency of clinical exacerbations, thus identifying promising biomarkers and therapeutic targets for difficult-to-treat
P.a infections
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