Microbes use transporters to regulate the release of metabolites based on value

Abstract

Microbial interactions are shaped by the exchange of metabolites, ranging from intermediates in central carbon metabolism to amino acids, vitamins and fermentation by-products. While specific metabolic processes such as overflow metabolism are well documented, a general principle explaining the chemical diversity of metabolite release and the variation in individual release rates remains elusive. Here, using a combination of computational and experimental approaches on seven different microbes, we show that release rates are negatively correlated with the value of metabolites, and that this relationship explains more variability in release rates than other frequently associated factors. By measuring metabolite release from 67 E. coli mutants lacking individual transport genes, we find that transporters both cause and counteract net metabolite release. These findings suggest that metabolite release constitutes a fitness cost that microbes have evolved to reduce, while revealing the underlying transport mechanism. This unifying explanation reshapes our understanding of how microbial interactions emerge and persist.