Dynamic proteome allocation regulates the profile of interaction of auxotrophic bacterial consortia

Abstract

Microbial ecosystems are composed of multiple species in constant metabolic exchange. A pervasive interaction in microbial communities is metabolic cross-feeding and occurs when the metabolic burden of producing costly metabolites is distributed between community members, in some cases for the benefit of all interacting partners. In particular, amino acid auxotrophies generate obligate metabolic inter-dependencies in mixed populations and have been shown to produce a dynamic profile of interaction that depends upon nutrient availability. However, identifying the key components that determine the pair-wise interaction profile remains a challenging problem, partly because metabolic exchange has consequences on multiple levels, from allocating proteomic resources at a cellular level to modulating the structure, function and stability of microbial communities. To evaluate how ppGpp-mediated resource allocation drives the population-level profile of interaction, here we postulate a multi-scale mathematical model that incorporates dynamics of proteome partition into a population dynamics model. We compare our computational results with experimental data obtained from co-cultures of auxotrophic Escherichia coli K12 strains under a range of amino acid concentrations and population structures. We conclude by arguing that the stringent response promotes cooperation by inhibiting the growth of fast-growing strains and promoting the synthesis of metabolites essential for other community members.

Minorities drive growth resumption in cross-feeding microbial communities

“…Metabolic specialization has been shown to evolve readily ( 8 , 11 – 14 ). This specialization can resolve biochemical conflicts between metabolic reactions, allowing individual microbes to optimize pathway lengths and providing consortia of interacting microbes with faster growth or higher yields ( 15 – 23 ).…”

“…When the external conditions change, microbes need to remodel their metabolism, but they can only resume growth once their metabolic partners have also adapted to the new conditions. This dilemma is particularly pronounced if microbes depend on each other for this metabolic remodeling ( 23 , 32 , 33 ). Such a situation arises whenever microbes, after a shift in environmental conditions, require cellular resources from their partners to produce the enzymes needed to resume growth.…”