Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections

• Published in: Metabolites Vol. 11; no. 2; p. 63
• Main Authors: Moyne, Oriane, Castelli, Florence, Bicout, Dominique J, Boccard, Julien, Camara, Boubou, Cournoyer, Benoit, Faudry, Eric, Terrier, Samuel, Hannani, Dalil, Huot-Marchand, Sarah, Léger, Claire, Maurin, Max, Ngo, Tuan-Dung, Plazy, Caroline, Quinn, Robert A, Attree, Ina, Fenaille, François, Toussaint, Bertrand, Le Gouëllec, Audrey
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.01.2021; MDPI
• Subjects: Adaptation; Antibiotic resistance; Antibiotics; Bacteriology; Bronchopulmonary infection; Clinical outcomes; Cluster analysis; Cystic fibrosis; Drug resistance; Evolution & development; Genomes; Genotype & phenotype; Human health and pathology; Infections; Infectious diseases; LC-HRMS; Life Sciences; Lungs; Metabolism; Metabolites; Metabolomics; Microbiology and Parasitology; multiscale data analysis; Mutation; P. aeruginosa; Pathogens; Patients; Phenotypes; polyamines; Pseudomonas aeruginosa; Pulmonology and respiratory tract; Virulence; Ala-Glu-mesodiaminopimelate; metabolomics; multiscale data analysis; cystic fibrosis; LC-HRMS; polyamines; P. aeruginosa; 37 polyamines
• ISSN: 2218-1989; 2218-1989
• DOI: 10.3390/metabo11020063

( ) 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 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 adaptation. Metabolic profiles were integrated with expression of bacterial phenotypes and clinical measurements following multiscale analysis methods. Our results highlighted significant associations between "metabotypes", expression of antibiotic resistance and virulence phenotypes, and frequency of clinical exacerbations, thus identifying promising biomarkers and therapeutic targets for difficult-to-treat infections.