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Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance
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Yu, Jason S. L., Correia-Melo, Clara, Zorrilla, Francisco, Herrera-Dominguez, Lucia, Wu, Mary Y., Hartl, Johannes, Campbell, Kate, Blasche, Sonja, Kreidl, Marco, Egger, Anna-Sophia, Messner, Christoph B., Demichev, Vadim, Freiwald, Anja, Mülleder, Michael, Howell, Michael, Berman, Judith, Patil, Kiran R., Alam, Mohammad Tauqeer and Ralser, Markus (2022) Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance. Nature Microbiology, 7 (4). pp. 542-555. doi:10.1038/s41564-022-01072-5 ISSN 2058-5276.
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WRAP-microbial-communities-form-rich-extracellular-metabolomes-foster-metabolic-interactions-promote-drug tolerance-Alam-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (15Mb) | Preview |
Official URL: 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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||||||||||||||||||||||||||||||||||||||
| SWORD Depositor: | Library Publications Router | ||||||||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Microbial ecology, Anti-infective agents, Drug resistance in microorganisms, Metabolites | ||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Nature Microbiology | ||||||||||||||||||||||||||||||||||||||||||
| Publisher: | Nature Publishing Group UK | ||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 2058-5276 | ||||||||||||||||||||||||||||||||||||||||||
| Official Date: | 21 March 2022 | ||||||||||||||||||||||||||||||||||||||||||
| Dates: |
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| Volume: | 7 | ||||||||||||||||||||||||||||||||||||||||||
| Number: | 4 | ||||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 542-555 | ||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1038/s41564-022-01072-5 | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 21 April 2022 | ||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 22 April 2022 | ||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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