Analysis of the Streptococcus mutans proteome during acid and oxidative stress reveals modules of co-expression and an expanded role for the TreR transcriptional regulator

Abstract

Streptococcus mutans promotes a tooth-damaging dysbiosis in the oral microbiota because it can form biofilms and survive acid stress better than most of its health-associated, ecological competitors. Many of these commensals produce hydrogen peroxide, therefore S. mutans must manage both oxidative stress and acid stress with coordinated and complex physiological responses. In this study, the proteome of S. mutans was examined during regulated growth in acid and oxidative stresses, as well as in deletion mutants with impaired oxidative stress phenotypes, Δnox and ΔtreR. 607 proteins exhibited significantly different abundance levels across the conditions tested, and correlation network analysis identified several modules of co-expressed proteins that were responsive to the deletion of nox and/or treR, as well as acid and oxidative stress. The data provided evidence explaining the ROS-sensitive and mutacin-deficient phenotypes exhibited by the ΔtreR strain. SMU.1069-1070, a poorly understood LytTR system, had elevated abundance in the ΔtreR strain. S. mutans LytTR systems regulate mutacin production and competence, which may explain how TreR affects mutacin production. Furthermore, the gene cluster that produces mutanobactin, important in ROS tolerance, displayed reduced abundance in the ΔtreR strain. The role of Nox as a keystone in the oxidative stress response was also emphasized. This dataset illustrates, at high resolution, how the paradigm cariogenic species activates the stress responses which enable it to cause disease, and it provides oral microbiota researchers with a resource to both reexamine previous hypotheses regarding proteins of interest and explore newly identified co-expression modules and pathways.