Stress-Induced Cooperation Promotes Tolerance in Resource-Limited Auxotrophic Microbial Consortia

Microbial communities often rely on metabolic cooperation, especially under nutrient limitation, but how antibiotics influence these interactions remains unclear. Here, we show that exposure to chloramphenicol, a ribosome-targeting bacteriostatic antibiotic, promotes cooperation in auxotrophic Escherichia coli consortia. Using a proteome-partition model, we find that chloramphenicol-induced growth inhibition elevates levels of the alarmone ppGpp, shifting proteome allocation toward amino acid biosynthesis and export. This regulatory response enhances cross-feeding and supports cooperative growth, even under antibiotic stress. Laboratory experiments confirm that, under low amino acid availability, co-cultures of leucine and phenylalanine auxotrophs display greater tolerance to chloramphenicol than monocultures. Both our theoretical and experimental results reveal a feedback loop in which antibiotic stress strengthens metabolic interdependence, buffering growth inhibition and enhancing community-level tolerance.