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Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975748/ https://www.ncbi.nlm.nih.gov/pubmed/35314781 http://dx.doi.org/10.1038/s41564-022-01072-5 |
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author | 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 Ralser, Markus |
author_facet | 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 Ralser, Markus |
author_sort | Yu, Jason S. L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8975748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89757482022-04-07 Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance 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 Ralser, Markus Nat Microbiol Article 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. Nature Publishing Group UK 2022-03-21 2022 /pmc/articles/PMC8975748/ /pubmed/35314781 http://dx.doi.org/10.1038/s41564-022-01072-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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 Ralser, Markus Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
title | Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
title_full | Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
title_fullStr | Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
title_full_unstemmed | Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
title_short | Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
title_sort | microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975748/ https://www.ncbi.nlm.nih.gov/pubmed/35314781 http://dx.doi.org/10.1038/s41564-022-01072-5 |
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