Extracellular ATP is an environmental cue in bacteria

Abstract

In animals and plants extracellular ATP (eATP) functions as signalling molecule and regulates the immune response. During inflammation intestinal bacteria are exposed to elevated eATP originating from the mucosa. Whether bacteria respond to eATP is unclear. Here we show that non-pathogenic Escherichia coli responds to eATP at physiologically relevant concentrations by modifying its transcriptional and metabolic landscape. The use of a promoter library showed that the response to eATP is time-, dose- and medium-dependent. Genes related to lipid, amino acid, or vitamin metabolism were regulated. Metabolomics showed that eATP triggers enrichment of molecules with bioactive properties on the host or bacteria. Combined genome-scale modelling highlighted the global metabolic modifications. Moreover, eATP altered the sensitivity to antibiotics and antimicrobial peptides. Finally, in pathogens eATP controls the expression of virulence and fitness factors. Our results indicate that eATP is a signalling molecule in prokaryotes which globally regulates physiology, antimicrobial resistance, and virulence.