Extracellular ATP is an environmental cue in bacteria

In animals and plants extracellular ATP (eATP) functions as signal and regulates the immune response. During inflammation intestinal bacteria are exposed to elevated eATP originating from the mucosa. However, whether bacteria respond to eATP is unclear. Here we show that non-pathogenic Escherichia coli responds to eATP by modifying its transcriptional and metabolic landscapes. A genome-scale promoter library showed that the response is time-, concentration-, and medium-dependent and ATP-specific. Second messengers and genes related to metabolism, biofilm formation, and envelope stress were regulated downstream of eATP. Metabolomics confirmed that eATP triggers enrichment of compounds with bioactive properties on the host or bacteria. Combined genome-scale modelling revealed global metabolic and biomass building blocks modifications. Consequently, eATP altered the sensitivity to antibiotics and antimicrobial peptides. Finally, in pathogens, eATP controlled virulence factor expression. Our results indicate that eATP is an environmental cue in prokaryotes which broadly regulates physiology, antimicrobial resistance, and virulence.