dATP/ATP, a Multifunctional Nucleotide, Stimulates Bacterial Cell Lysis, Extracellular DNA Release and Biofilm Development

BACKGROUND: Signaling by extracellular adenosine 5'-triphosphase (eATP) is very common for cell-to-cell communication in many basic patho-physiological development processes. Rapid release of ATP into the extracellular environment from distressed or injured eukaryotic cells due to pathogens or other etiological factors can serve as a "danger signal", activating host innate immunity. However, little is known about how or whether pathogenic bacteria respond to this "danger signal". METHODS AND PRINCIPAL FINDINGS: Here we report that extracellular dATP/ATP can stimulate bacterial adhesion and biofilm formation via increased cell lysis and extracellular DNA (eDNA) release. We demonstrate that extracellular dATP/ATP also stimulates bacterial adherence in vitro to human bronchial epithelial cells. CONCLUSIONS AND SIGNIFICANCE: These data suggest that bacteria may sense extracellular dATP/ATP as a signal of "danger" and form biofilms to protect them from host innate immunity. This study reveals a very important and unrecognized phenomenon that both bacteria and host cells could respond to a common important signal molecule in a race to adapt to the presence of one another. We propose that extracellular dATP/ATP functions as an "inter-domain" warning signal that serves to induce protective measures in both Bacterial and Eukaryotic cells.