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

ABSTRACT 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.