Nanotube-mediated cross-feeding couples the metabolism of interacting bacterial cells

Abstract

Bacteria frequently engage in cross-feeding interactions that involve an exchange of metabolites with other micro- or macroorganisms. The often obligate nature of these associations, however, hampers manipulative experiments, thus limiting our mechanistic understanding of the ecophysiological consequences that result for the organisms involved. Here we address this issue by taking advantage of a well-characterised experimental model system, in which auxotrophic genotypes of E. coli derive essential amino acid from prototrophic donor cells using intercellular nanotubes. Surprisingly, donor-recipient cocultures revealed that the mere presence of auxotrophic genotypes in coculture was sufficient to increase amino acid production levels in donor cells. Subsequent experiments unravelled that this effect was due to the depletion of amino acid concentrations in the cytoplasm of donor cells, which delayed feedback inhibition of the corresponding amino acid biosynthetic pathway. This finding indicates that in newly established mutualistic associations, an intercellular regulation of exchanged metabolites can simply emerge from the architecture of the underlying biosynthetic pathways, rather than through the evolution of new regulatory mechanisms. Taken together, our results show that a single loss-of-function mutation can physiologically couple the metabolism of two cross-feeding cells in a source-sink-like relationship.