Emergence of community behaviors in the gut microbiota upon drug treatment.

community resilience drug bioaccumulation drug biotransformation growth inhibition human-targeted drugs metabolomics microbiology

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
19 Sep 2024
Historique:
received: 14 06 2023
revised: 26 06 2024
accepted: 20 08 2024
medline: 26 9 2024
pubmed: 26 9 2024
entrez: 25 9 2024
Statut: aheadofprint

Résumé

Pharmaceuticals can directly inhibit the growth of gut bacteria, but the degree to which such interactions manifest in complex community settings is an open question. Here, we compared the effects of 30 drugs on a 32-species synthetic community with their effects on each community member in isolation. While most individual drug-species interactions remained the same in the community context, communal behaviors emerged in 26% of all tested cases. Cross-protection during which drug-sensitive species were protected in community was 6 times more frequent than cross-sensitization, the converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that the resilience of microbial communities can collapse when perturbations get stronger. By metabolically profiling drug-treated communities, we showed that both drug biotransformation and bioaccumulation contribute mechanistically to communal protection. As a proof of principle, we molecularly dissected a prominent case: species expressing specific nitroreductases degraded niclosamide, thereby protecting both themselves and sensitive community members.

Identifiants

pubmed: 39321801
pii: S0092-8674(24)00966-8
doi: 10.1016/j.cell.2024.08.037
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Sarela Garcia-Santamarina (S)

European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany; European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.

Michael Kuhn (M)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.

Saravanan Devendran (S)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.

Lisa Maier (L)

European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany.

Marja Driessen (M)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.

André Mateus (A)

European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany.

Eleonora Mastrorilli (E)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.

Ana Rita Brochado (AR)

European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany.

Mikhail M Savitski (MM)

European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany.

Kiran R Patil (KR)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany. Electronic address: kp533@mrc-tox.cam.ac.uk.

Michael Zimmermann (M)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany. Electronic address: michael.zimmermann@embl.de.

Peer Bork (P)

European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany; Max Delbrück Center for Molecular Medicine, Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany. Electronic address: bork@embl.de.

Athanasios Typas (A)

European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany; European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany. Electronic address: typas@embl.de.

Classifications MeSH