Bacterial infections of the mucosal epithelium initiate inflammation of the local tissues, which leads to
changes in the molecular profile of the extracellular milieu, including increases in extracellular ATP, and
its ecto-enzymatic and hydrolytic degradation products ADP and adenosine. Extracellular ATP and
adenosine function as signaling molecules at purinergic receptors which have been shown to regulate
several key aspects of immune cell function. Information has been quite limited, however, on how this
may alter bacterial growth in the inflamed tissue. Here we demonstrate that stimulation of Chlamydia
trachomatis infected epithelial cells with micromolar extracellular ATP, ADP and adenosine significantly
impairs growth of the bacteria. The response to adenosine is mediated by the A2b receptor, while the
effects of ATP and ADP suggest involvement of P2X4 receptors. Chlamydial growth is reversibly
inhibited, and the bacteria return to normal growth kinetics following removal of the stimulus. This
suggests that extracellular adenosine and adenine nucleotides are important for local control of C.
trachomatis at infected mucosal epithelium, and that further characterization of the intracellular
mechanisms employed by the host could lead to improved methods of treating this important pathogen.