Virulence adaption to environment promotes the age-dependent nasal colonization of .

is an important human commensal bacteria colonizing the human body, especially the nasal cavity. The nasal carriage can be a source of bacteremia. However, the bacterial factors contributing to nasal colonization are not completely understood. By analysing strains from the nasal cavity of the children, young adults, and seniors, we found that the low activity of the SaeRS two-component system (TCS) is an important determinant for to colonize in seniors. The senior group isolates of showed a rather distinct sequence type composition as compared with other age group isolates. The senior group isolates showed not only a lower gene carriage of enterotoxins a, c, and q but also lower hemolytic activity against human red blood cells. Of regulators affecting hemolysin production (i.e. , , , , and ), only the SaeRS TCS showed an age-dependent decrease of activity. The decreased virulence and better colonization ability of the senior group isolates of were confirmed in the mouse model. The senior group isolates showed the lowest survival and the best adhesion and colonizing ability. Also, the senior nasal secretions supported survival better than the child and young adult nasal secretions. These results indicated that the senior nasal cavity favours colonization of with higher adhesion and lower virulence, to which the reduced SaeRS TCS activity contributes. Taken together, our results illustrate an example of bacterial adaptation to the changing host environment.