Extracellular ATP is an environmental cue in bacteria

Area of Science:

• Microbiology
• Biochemistry
• Molecular Biology

Background:

• Extracellular ATP (eATP) is a known signaling molecule in animals and plants, modulating immune responses.
• Intestinal bacteria encounter elevated eATP levels during inflammation, but their response to it remains largely unknown.

Purpose of the Study:

• To investigate whether bacteria, specifically Escherichia coli, respond to extracellular ATP (eATP).
• To elucidate the molecular and metabolic mechanisms underlying bacterial responses to eATP.
• To determine the functional consequences of eATP signaling in bacteria, including effects on antimicrobial resistance and virulence.

Main Methods:

• Utilized a genome-scale promoter library to assess eATP-dependent gene regulation.
• Employed metabolomics to analyze changes in bacterial metabolite profiles.
• Integrated genome-scale modeling to understand global metabolic shifts.
• Tested the impact of eATP on bacterial sensitivity to antibiotics and antimicrobial peptides.

Main Results:

• Escherichia coli demonstrated a time-, concentration-, and medium-dependent, ATP-specific response to eATP.
• eATP modulated second messenger pathways and regulated genes involved in metabolism, biofilm formation, and envelope stress.
• Metabolomic and modeling analyses revealed significant alterations in bacterial metabolic networks and biomass composition.
• Bacterial exposure to eATP affected sensitivity to antibiotics and antimicrobial peptides.
• In pathogenic bacteria, eATP was found to control virulence factor expression.

Conclusions:

• Extracellular ATP (eATP) acts as a significant environmental cue for prokaryotes, broadly regulating their physiology.
• Bacterial responses to eATP impact antimicrobial resistance and virulence, suggesting a role in host-microbe interactions.
• eATP signaling in bacteria represents a novel regulatory mechanism with implications for understanding microbial ecology and pathogenesis.