Fig. 1

Schematic/work flow of experimental design – From evolution to emergence. a Adaptive laboratory evolution (ALE) of antibiotic resistant populations of C. violaceum under sub-lethal concentrations of antibiotic. 5 μl of overnight culture of C. violaceum was evenly spread onto LB agar plates with respective antibiotic (10 μg/ml) and were incubated at 30 °C until colonies appeared on the agar plates. After clonal purification the resistant populations were cultured and showed characteristic violet color pigment, violacein. ChlR shows lower intensity of pigmentation while StrpR showed higher levels as compared to WT. b Primary phenotypic profiling performed to confirm the evolution of resistance against the two antibiotics using minimum inhibitory concentration (MIC) and violacein estimation (refer Methods for details). c Systems Biology approach used in this study with basic growth profiling, metabolite supplementation experiments, genotypic profiling using whole genome sequencing (WGS), HRMS metabolomics, and in silico structural analysis of variants and flux balance modeling using iDB149 network with constraints derived from in house data. This scalable pipeline allows understanding the genotype-phenotype relationship of the resistant pathogens