Engineering microbial consortia for distributed signal processing

A central goal in biology is to infer input signals from measurable readouts. Engineered biosensors are usually built to respond selectively to single inputs, so crosstalk between sensors must be removed through laborious, context-specific orthogonalization. Here we show that multiplexed concentrations can be inferred without eliminating crosstalk. We distribute sensing across a microbial community and decode its time-resolved collective response, which can disambiguate combinations of chemical inputs even when individual sensors show crosstalk or respond indirectly. A computational framework coupling kinetic modeling with machine learning maps these community dynamics to input concentrations. We demonstrate quantitative inference in communities with low or high sensor crosstalk, in communities that respond only indirectly to antibiotic combinations, and in pooled hospital sink water spiked with target analytes. By tolerating non-orthogonal, cross-reactive, and indirect responses, distributed dynamic sensing broadens the range of biological systems usable for multiplexed measurement, wherever input combinations produce reproducible, distinguishable response trajectories. Multiplexed biosensing is often limited by crosstalk between sensors. Here, authors distribute sensing across microbial communities and use timer-resolved modelling and machine learning to infer multiple chemical concentrations from cross-reactive and indirect responses.