ROLE OF EXTRACELLULAR ATP IN THE PATHOGENESIS OF PERIODONTAL DISEASE

Abstract

ATP is a danger assocaited molecular pattern to alert the immune system of an impending danger. In this study, we found that Aggregatibacter actinomycetemcomitans, a pathogen associated with aggressive periodontal disease secreted ATP extracellularly to elicit chemokine response in innate immune cells. Since periodontal bacteria exist as a community in plaque biofilm, we hypothesized that eATP at sites of tissue damage could function as a nutrient or signaling molecule in bacterial communities. Indeed, eATP induced dispersal of Fusobacterium nucleatum biofilm. Furthermore, biofilm dispersed F. nucleatum was more virulent compared to its planktonic or biofilm counterparts. In our attempt to delineate the mechanism of secretion of ATP in A. actinoycetemcomitans, we developed a protocol to generate random libraries of A. actinoycetemcomitans mutants using the Himar1 transposon system. Collectively, this work has provided new insights on previously unrecognized sources and roles of eATP, and their potential implications in periodontal disease.