LiaSR two-component system modulates the oxidative stress response in Streptococcus mutans

Many commensal bacteria of the human oral microbiome can produce reactive oxygen species (ROS). ROS will inhibit the colonization of Streptococcus mutans (S. mutans), a major pathogenic bacteria in dental caries. The LiaSR two-component system in S. mutans can sense and respond to environmental oxidative stress. However, the molecular details of the LiaSR two-component system and oxidative stress response have been unclear. In this study, we aimed to elucidate the underlying mechanisms of the LiaSR two-component system and the mediated oxidative stress response in S. mutans. We performed the H2O2 killing assay, Confocal laser scanning microscopy, and 2,7-Dichlorofluoresce diacetate staining assay to evaluate the sensitivity of S. mutans to H2O2. The propidium iodide probe and TUNEL kit were used to detect the membrane permeability and DNA fragmentation. Quantitative real-time PCR was conducted to analyze the expression level of underlying regulated genes. The liaS and liaR deficient mutants were particularly sensitive to H2O2 compared to their wild strain S. mutans 593, which was previously isolated from a caries-active patient. The intracellular levels of ROS and membrane permeability increased in the mutants. The TUNEL assay showed that the rate of DNA fragmentation in the liaR mutant was higher compared to the wild strain and liaS mutant. Relative expression of the spxA2 gene in the mutants was lower than in the wild strain. The dpr and dinB genes were downregulated in the liaR mutant. These results indicated that the LiaSR two-component system mediated influence on spxA2 expression in S. mutans and contributed to membrane homeostasis, which was involved in the oxidative response process. S. mutans could also elevate the dpr and the dinB genes, which depend on the liaR component in the LiaSR system, may help reduce the DNA damage caused by ROS. This study provides valuable insights into the mechanisms of the LiaSR two-component system in the oxidative stress response of S. mutans.