S. pneumoniae is a main human pathogen that survives to acidic environment through the Acid Tolerance Response (ATR) mechanism. We previously described the acidic-stress induced autolysis (ASIL) that release virulence factors favoring pathogenesis and that F0F1-ATPase is involved in the acidic stress response. The atpC mutants (atpC encodes the subunit c of this enzyme) showed a repressed ATR, but an increased ASIL.
Here, we found that this pathogen was able to survive several hours inside A549 pneumocytes or macrophages RAW 267.4. We showed that F0F1-ATPase, and consequently ATR, are necessary for intracellular life of the pneumococcus in macrophages. In addition, we described that ATR induction and intracellular life of pneumococci in pneumocytes are controlled by ComDE and CiaRH, two-component systems (TCS) that had been involved in the ASIL mechanism, showing opposite roles. Briefly, CiaRH is essential for ATR (ComE represses activation) whereas ComE is necessary for ASIL (CiaRH protects induction). These results suggested that both TCSs control these antagonistic processes, either in vitro or in a cellular model.
This is the first report of TCSs that acts like checkpoints to control a stress response and to decide between a survival and a suicide mechanism in a cell model. This biological model contributes to the knowledge of bacterial pathogenesis under stress conditions in host tissues, where pathogens need to survive to establish infections.
