Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.

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Correia-Melo, Clara  ORCID logo  https://orcid.org/0000-0001-6062-1472
Zorrilla, Francisco 
Herrera-Dominguez, Lucia  ORCID logo  https://orcid.org/0000-0001-8276-2241

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.


Funder: United Arab Emirates University (UAEU); doi: https://doi.org/10.13039/501100006013

Article, /631/326/2565/855, /631/326/22, /13/31, /13/44, /14/34, /14/35, /38/47, /82/80, /96/63, /82/58, article
Journal Title
Nat Microbiol
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Springer Science and Business Media LLC
Francis Crick Institute (Francis Crick Institute Limited) (FC001134, FC001134FC001134, FC001134, FC001134, FC001134, FC001134, FC001134)
Wellcome Trust (Wellcome) (IA 200829/Z/16/Z, IA 200829/Z/16/Z, IA 200829/Z/16/Z)
RCUK | Medical Research Council (MRC) (MC_UU_00025/11, MC_UU_00025/11, MC_UU_00025/11)
Wellcome Trust (Wellcome) (IA 200829/Z/16/Z, IA 200829/Z/16/Z)
Israel Science Foundation (ISF) (#997/18)