Ratiometric growth-rate control enables robust coexistence in competing microbial consortia

Abstract

Maintaining a prescribed composition in engineered microbial consortia is difficult because small fitness differences can drive competitive exclusion. We study a two-strain consortium in continuous culture and develop a feedback architecture that regulates composition by selectively slowing the fast strain as a function of the population ratio. At the population level, we derive an idealized ratio-feedback law with a tunable positive coexistence equilibrium. We then propose a biomolecular realization using orthogonal quorum sensing, an sRNA-based ratiometric controller, and a ppGpp-mediated growth actuator. Exploiting the separation between slow population growth and faster intracellular controller dynamics, we use singular perturbation theory to show that, for sufficiently fast controller dynamics, the full implementation model inherits the coexistence equilibrium and its local stability properties from the reduced model. Numerical simulations validate the reduction and show how weaker timescale separation or loss of the assumed molecular regime degrades performance.