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

Maintaining a consistent mix of bacteria within engineered microbial communities is challenging, as minor differences in their efficiency can lead to one species entirely replacing the others. Researchers investigated this issue in a laboratory setting, focusing on a pair of bacterial strains within a continuous culture system. They devised a feedback system that adjusts the growth rate of the faster strain in response to the population ratio between the two strains.

This ratio-feedback law provides an idealized, adjustable equilibrium point that promotes coexistence among the competing microbes. To implement this idea, the team devised a biological solution involving distinct quorum sensing mechanisms, an RNA-based ratiometric control component, and a molecule called ppGpp that regulates cellular growth.

By separating the slow growth of the microbes from the rapid controller dynamics, they applied a mathematical technique called singular perturbation theory. This approach demonstrated that, under the right conditions where the controller operates swiftly, the complete system model inherits the desired coexistence equilibrium and its stability properties from the simplified model used to describe the underlying biology.

Computer simulations confirmed the accuracy of this reduction and shed light on the delicate balance required between the different timescales involved. If this separation becomes less pronounced or the molecular regime assumed in the model is compromised, the system's performance would suffer.