Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.
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Authors
Zorrilla, Francisco
Campbell, Kate
Blasche, Sonja
Kreidl, Marco
Messner, Christoph B
Demichev, Vadim
Freiwald, Anja
Mülleder, Michael
Patil, Kiran R
Publication Date
2022-04Journal Title
Nat Microbiol
ISSN
2058-5276
Publisher
Springer Science and Business Media LLC
Volume
7
Issue
4
Pages
542-555
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Yu, J. S., Correia-Melo, C., Zorrilla, F., Herrera-Dominguez, L., Wu, M. Y., Hartl, J., Campbell, K., et al. (2022). Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.. Nat Microbiol, 7 (4), 542-555. https://doi.org/10.1038/s41564-022-01072-5
Abstract
Microbial communities are composed of cells of varying metabolic capacity, and regularly include auxotrophs that lack essential metabolic pathways. Through analysis of auxotrophs for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial communities obtained as part of the Earth Microbiome Project (EMP), and study of auxotrophic-prototrophic interactions in self-establishing metabolically cooperating yeast communities (SeMeCos), we reveal a metabolically imprinted mechanism that links the presence of auxotrophs to an increase in metabolic interactions and gains in antimicrobial drug tolerance. As a consequence of the metabolic adaptations necessary to uptake specific metabolites, auxotrophs obtain altered metabolic flux distributions, export more metabolites and, in this way, enrich community environments in metabolites. Moreover, increased efflux activities reduce intracellular drug concentrations, allowing cells to grow in the presence of drug levels above minimal inhibitory concentrations. For example, we show that the antifungal action of azoles is greatly diminished in yeast cells that uptake metabolites from a metabolically enriched environment. Our results hence provide a mechanism that explains why cells are more robust to drug exposure when they interact metabolically.
Keywords
Drug Tolerance, Metabolic Networks and Pathways, Metabolome, Microbial Interactions, Microbiota
Sponsorship
European Research Council (951475)
Medical Research Council (MC_UU_00025/11)
Wellcome Trust (IA 200829/Z/16/Z, 200829/Z/16/Z, FC001134)
Israel Science Foundation (ISF) (#997/18)
Versus Arthritis (FC001134)
Francis Crick Institute (Francis Crick Institute Limited) (FC001134FC001134)
Identifiers
35314781, PMC8975748
External DOI: https://doi.org/10.1038/s41564-022-01072-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336390
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