Microbiome-mediated fructose depletion restricts murine gut colonization by vancomycin-resistant Enterococcus.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
13 12 2022
Historique:
received: 28 09 2020
accepted: 30 11 2022
entrez: 13 12 2022
pubmed: 14 12 2022
medline: 16 12 2022
Statut: epublish

Résumé

Multidrug-resistant organisms (MDRO) are a major threat to public health. MDRO infections, including those caused by vancomycin-resistant Enterococcus (VRE), frequently begin by colonization of the intestinal tract, a crucial step that is impaired by the intestinal microbiota. However, the specific members of the microbiota that suppress MDRO colonization and the mechanisms of such protection are largely unknown. Here, using metagenomics and mouse models that mimic the patients' exposure to antibiotics, we identified commensal bacteria associated with protection against VRE colonization. We further found a consortium of five strains that was sufficient to restrict VRE gut colonization in antibiotic treated mice. Transcriptomics in combination with targeted metabolomics and in vivo assays indicated that the bacterial consortium inhibits VRE growth through nutrient depletion, specifically by reducing the levels of fructose, a carbohydrate that boosts VRE growth in vivo. Finally, in vivo RNA-seq analysis of each strain of the consortium in combination with ex vivo and in vivo assays demonstrated that a single bacterium (Olsenella sp.) could recapitulate the effect of the consortium. Our results indicate that nutrient depletion by specific commensals can reduce VRE intestinal colonization, which represents a novel non-antibiotic based strategy to prevent infections caused by this multidrug-resistant organism.

Identifiants

pubmed: 36513659
doi: 10.1038/s41467-022-35380-5
pii: 10.1038/s41467-022-35380-5
pmc: PMC9748033
doi:

Substances chimiques

Vancomycin 6Q205EH1VU
Fructose 30237-26-4
Anti-Bacterial Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

7718

Informations de copyright

© 2022. The Author(s).

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Auteurs

Sandrine Isaac (S)

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana - FISABIO, Valencia, Spain. isaacsandrine8488@gmail.com.
Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. isaacsandrine8488@gmail.com.

Alejandra Flor-Duro (A)

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana - FISABIO, Valencia, Spain.

Gloria Carruana (G)

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana - FISABIO, Valencia, Spain.

Leonor Puchades-Carrasco (L)

Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.

Anna Quirant (A)

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana - FISABIO, Valencia, Spain.

Marina Lopez-Nogueroles (M)

Analytical Unit Platform, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.

Antonio Pineda-Lucena (A)

Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
Molecular Therapeutics Program, Centro de Investigación Médica Aplicada, University of Navarra, Pamplona, Spain.

Marc Garcia-Garcera (M)

Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.

Carles Ubeda (C)

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana - FISABIO, Valencia, Spain. ubeda_carmor@gva.es.
CIBER en Epidemiología y Salud Pública, Madrid, Spain. ubeda_carmor@gva.es.

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Classifications MeSH