Emergent phenotypic heterogeneity in synthetic cross-feeding consortia driven by heterogeneous metabolite distribution.

Cooperation is crucial for constructions of all levels of life. But cooperation is often vulnerable, and understanding the underlying causes remains a grand challenge in ecology and evolution. Here we, by constructing a synthetic cooperative system consisting of two genetically engineered Escherichia coli strains with metabolic cross-feeding, demonstrate that cross-feeding, though it promotes the growth, amplifies cell noise of both strain populations in the bacterial consortium. The emergent phenotypic heterogeneity, expressed as the induced increase in cell noise by cross-feeding, is attributed mainly to enhanced resource heterogeneity and subsequent variation in gene expression among cells within each population. We further show that the positive interaction (including mutualism, commensalism and/or exploitation) also induces phenotypic heterogeneity in distinct microbial consortia consisting of bacterial strains isolated from aquatic, soil or rhizospheric environments. Our results reveal a cooperation-induced trade-off between population fitness and homogeneity, highlighting the importance of stochasticity in understanding the evolution of cooperation in microbiomes in nature.