Cell-to-cell heterogeneity emerges as consequence of metabolic cooperation in a synthetic yeast community.
Cells that grow together respond heterogeneously to stress even when they are genetically similar. Metabolism, a key determinant of cellular stress tolerance, may be one source of this phenotypic heterogeneity, however, this relationship is largely unclear. We used self-establishing metabolically cooperating (SeMeCo) yeast communities, in which metabolic cooperation can be followed on the basis of genotype, as a model to dissect the role of metabolic cooperation in single-cell heterogeneity. Cells within SeMeCo communities showed to be highly heterogeneous in their stress tolerance, while the survival of each cell under heat or oxidative stress, was strongly determined by its metabolic specialization. This heterogeneity emerged for all metabolite exchange interactions studied (histidine, leucine, uracil, and methionine) as well as oxidant (H2 O2 , diamide) and heat stress treatments. In contrast, the SeMeCo community collectively showed to be similarly tolerant to stress as wild-type populations. Moreover, stress heterogeneity did not establish as sole consequence of metabolic genotype (auxotrophic background) of the single cell, but was observed only for cells that cooperated according to their metabolic capacity. We therefore conclude that phenotypic heterogeneity and cell to cell differences in stress tolerance are emergent properties when cells cooperate in metabolism.
Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Kate
K
Campbell
Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Jakob
J
Vowinckel
Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom. mr559@cam.ac.uk.|The Francis Crick Institute, Mill Hill laboratory, London, United Kingdom. mr559@cam.ac.uk.
Markus
M
Ralser
D018920:Coculture Techniques; D005838:Genotype; D006358:Hot Temperature; D055442:Metabolome; D056265:Microbial Interactions; D050296:Microbial Viability; D018384:Oxidative Stress; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism*; D058615:Synthetic Biology
Heat stress; Metabolic cooperation; Oxidative stress; Self-establishing metabolically cooperating yeast community