Metabolic heterogeneity and cross-feeding within isogenic yeast populations captured by DILAC.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
30
06
2022
accepted:
13
12
2022
pubmed:
17
2
2023
medline:
7
3
2023
entrez:
16
2
2023
Statut:
ppublish
Résumé
Genetically identical cells are known to differ in many physiological parameters such as growth rate and drug tolerance. Metabolic specialization is believed to be a cause of such phenotypic heterogeneity, but detection of metabolically divergent subpopulations remains technically challenging. We developed a proteomics-based technology, termed differential isotope labelling by amino acids (DILAC), that can detect producer and consumer subpopulations of a particular amino acid within an isogenic cell population by monitoring peptides with multiple occurrences of the amino acid. We reveal that young, morphologically undifferentiated yeast colonies contain subpopulations of lysine producers and consumers that emerge due to nutrient gradients. Deconvoluting their proteomes using DILAC, we find evidence for in situ cross-feeding where rapidly growing cells ferment and provide the more slowly growing, respiring cells with ethanol. Finally, by combining DILAC with fluorescence-activated cell sorting, we show that the metabolic subpopulations diverge phenotypically, as exemplified by a different tolerance to the antifungal drug amphotericin B. Overall, DILAC captures previously unnoticed metabolic heterogeneity and provides experimental evidence for the role of metabolic specialization and cross-feeding interactions as a source of phenotypic heterogeneity in isogenic cell populations.
Identifiants
pubmed: 36797484
doi: 10.1038/s41564-022-01304-8
pii: 10.1038/s41564-022-01304-8
pmc: PMC9981460
doi:
Substances chimiques
Amino Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
441-454Subventions
Organisme : Cancer Research UK
ID : FC001134
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001134
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001134
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001134
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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