ABSTRACT
Symbiotic associations have radically shaped the diversity and complexity of life on earth. Many known symbioses represent physiological fusions of previously independent organisms, in which metabolites are traded between interacting partners in intricate ways. The first steps leading to this tight entanglement, however, remain unknown. Here we demonstrate that unidirectional cross-feeding of essential amino acids between two bacterial cells can already couple their metabolisms in a source-sink-like relationship. Auxotrophic recipients used intercellular nanotubes to derive amino acids from other bacterial cells. Removal of cytoplasmic amino acids in this way increased the amino acid production of donor cells by delaying feedback inhibition of the corresponding amino acid biosynthetic pathway. Strikingly, even though donor cells produced all the focal amino acids recipients required to grow, this additional metabolic burden did not incur detectable fitness costs. Our results demonstrate that one loss-of-function mutation is sufficient to couple the metabolic networks of two organisms, thus resulting in a functional fusion of two previously independent individuals.
