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Open AccessArticle

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

1
Département de Biochimie, Faculté de médecine de Grenoble, CNRS, CHU Grenoble Alpes, University Grenoble Alpes, Grenoble INP*, TIMC-IMAG, 38000 Grenoble, France
2
Département Médicaments et Technologies pour la Santé (DMTS), University Paris-Saclay, CEA, INRAE, MetaboHUB, 91191 Gif sur Yvette, France
3
Biomathematics and Epidemiology EPSP-TIMC, Veterinary Campus of Lyon, VetAgro Sup, 69280 Marcy l’Etoile, France
4
Laue-Langevin Institute, Theory Group, 71 Avenue des Martyrs, 38042 Grenoble, France
5
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland
6
CHU Grenoble Alpes, Service Hospitalier Universitaire de Pneumologie, Centre de Compétence de la Mucoviscidose, 38000 Grenoble, France
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Department of Veterinary and biological sciences, Université Claude Bernard Lyon 1, University Lyon 1, VetAgro Sup, UMR Ecologie Microbienne, CNRS 5557, INRA 1418, 69280 Marcy L’Etoile, France
8
CEA, INSERM, CNRS, Bacterial Pathogenesis and Cellular Responses, University Grenoble Alpes, UMR 1036/ERL 5261, 17 avenue des Martyrs, 38054 Grenoble, France
9
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
Present address: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92161, USA.
Metabolites 2021, 11(2), 63; https://doi.org/10.3390/metabo11020063
Received: 24 December 2020 / Revised: 14 January 2021 / Accepted: 15 January 2021 / Published: 21 January 2021
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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 View Full-Text
Keywords: cystic fibrosis; metabolomics; multiscale data analysis; LC-HRMS; P. aeruginosa; polyamines; Ala-Glu-mesodiaminopimelate cystic fibrosis; metabolomics; multiscale data analysis; LC-HRMS; P. aeruginosa; polyamines; Ala-Glu-mesodiaminopimelate
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MDPI and ACS Style

Moyne, O.; Castelli, F.; Bicout, D.J.; Boccard, J.; Camara, B.; Cournoyer, B.; Faudry, E.; Terrier, S.; Hannani, D.; Huot-Marchand, S.; Léger, C.; Maurin, M.; Ngo, T.-D.; Plazy, C.; Quinn, R.A.; Attree, I.; Fenaille, F.; Toussaint, B.; Le Gouëllec, A. Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections. Metabolites 2021, 11, 63. https://doi.org/10.3390/metabo11020063

AMA Style

Moyne O, Castelli F, Bicout DJ, Boccard J, Camara B, Cournoyer B, Faudry E, Terrier S, Hannani D, Huot-Marchand S, Léger C, Maurin M, Ngo T-D, Plazy C, Quinn RA, Attree I, Fenaille F, Toussaint B, Le Gouëllec A. Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections. Metabolites. 2021; 11(2):63. https://doi.org/10.3390/metabo11020063

Chicago/Turabian Style

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. 2021. "Metabotypes of Pseudomonas aeruginosa Correlate with Antibiotic Resistance, Virulence and Clinical Outcome in Cystic Fibrosis Chronic Infections" Metabolites 11, no. 2: 63. https://doi.org/10.3390/metabo11020063

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