We focused our attention on the first barrier that this pathogen must cross to establish an infection, and we hypothesized that intracellular survival in pneumocytes should be important for S. pneumoniae. The ΔstkP, ΔcomE, and comET128A mutants were tested in the pneumococcal infection model in A549 pneumocytes, and they revealed an increased survival compared with wt. Thus, we conclude that this survival could have been caused by increasing their capacity of ATR, decreasing the H2O2 production and modifying the cell wall biosynthesis to repress ASIL (Fig 9). This evidence concerns the gene ATR and pneumococcal infection.