Institute for Stem Cell Science and Regenerative Medicine (inStem), Bengaluru 560065, India.
Genetics. 2021 Oct 2;219(2). doi: 10.1093/genetics/iyab109.
In fluctuating nutrient environments, isogenic microbial cells transition into "multicellular" communities composed of phenotypically heterogeneous cells, showing functional specialization. In fungi (such as budding yeast), phenotypic heterogeneity is often described in the context of cells switching between different morphotypes (e.g., yeast to hyphae/pseudohyphae or white/opaque transitions in Candida albicans). However, more fundamental forms of metabolic heterogeneity are seen in clonal Saccharomyces cerevisiae communities growing in nutrient-limited conditions. Cells within such communities exhibit contrasting, specialized metabolic states, and are arranged in distinct, spatially organized groups. In this study, we explain how such an organization can stem from self-organizing biochemical reactions that depend on special metabolites. These metabolites exhibit plasticity in function, wherein the same metabolites are metabolized and utilized for distinct purposes by different cells. This in turn allows cell groups to function as specialized, interdependent cross-feeding systems which support distinct metabolic processes. Exemplifying a system where cells exhibit either gluconeogenic or glycolytic states, we highlight how available metabolites can drive favored biochemical pathways to produce new, limiting resources. These new resources can themselves be consumed or utilized distinctly by cells in different metabolic states. This thereby enables cell groups to sustain contrasting, even apparently impossible metabolic states with stable transcriptional and metabolic signatures for a given environment, and divide labor in order to increase community fitness or survival. We speculate on possible evolutionary implications of such metabolic specialization and division of labor in isogenic microbial communities.
在波动的营养环境中，同基因的微生物细胞会转变为由表型异质细胞组成的“多细胞”群落，表现出功能特化。在真菌（如出芽酵母）中，表型异质性通常是在细胞在不同形态之间切换的背景下描述的（例如，酵母到菌丝/假菌丝或白色/不透明的转变在白色念珠菌中）。然而，在营养有限条件下生长的克隆酿酒酵母群落中，可以看到更基本形式的代谢异质性。这些群落中的细胞表现出不同的、专门的代谢状态，并以不同的、空间组织的群体排列。在这项研究中，我们解释了这种组织如何源于依赖特殊代谢物的自组织生化反应。这些代谢物在功能上具有可塑性，即相同的代谢物被不同的细胞代谢和用于不同的目的。这反过来又允许细胞群作为专门的、相互依赖的交叉喂养系统发挥作用，支持不同的代谢过程。以表现出糖异生或糖酵解状态的细胞为例，我们强调了可用代谢物如何驱动有利的生化途径产生新的、限制资源。这些新资源本身可以被不同代谢状态的细胞以不同的方式消耗或利用。因此，细胞群可以在给定的环境中维持稳定的转录和代谢特征的不同代谢状态，从而分工合作，以提高群落的适应性或生存能力。我们推测了这种代谢特化和同基因微生物群落中分工的可能进化意义。
