Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
16
03
2021
accepted:
28
01
2022
pubmed:
23
3
2022
medline:
6
4
2022
entrez:
22
3
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35314781
doi: 10.1038/s41564-022-01072-5
pii: 10.1038/s41564-022-01072-5
pmc: PMC8975748
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
542-555Subventions
Organisme : Arthritis Research UK
ID : FC001134
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00025/11
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001134
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001134
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200829/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001134
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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