Deciphering the role of SMU.1147 in peptide-mediated signaling and competence in Streptococcus mutans.

Abstract

Streptococcus mutans is a primary cariogenic pathogen involved in dental biofilm formation, a major virulence factor in the development of dental caries. In S. mutans, the competence-stimulating peptide (CSP), encoded by comC, plays a critical role in environmental stress response, growth regulation, and virulence expression. In this study, we performed transcriptome analysis to investigate the role of SMU.1147, a unique core gene in S. mutans, in biological pathways related to transport, defense responses, and environmental sensing. The deletion of SMU.1147 led to the upregulation of genes involved in carbohydrate uptake and metabolism, particularly phosphotransferase system (PTS) transporters, thereby enhancing the sugar transport capacity. However, despite increased sugar uptake, the mutant strain did not show significant changes in growth rate or ATP production and displayed slightly reduced organic acid production. Additionally, the mutant exhibited significantly reduced cell viability after an 8-h incubation compared to the parental strain. Notably, genes associated with CSP-dependent signal transduction and stress defense, such as comX, comR, htrA, scnRK, and ciaRH, were downregulated in the mutant strain. Furthermore, stress-related genes, including spxA2, clpP, and clpX, were significantly downregulated, suggesting compromised protein quality control and oxidative stress responses. Our findings suggest that SMU.1147 plays a critical role in regulating peptide-mediated signaling, metabolic coordination, and environmental adaptation in S. mutans, positioning it as a key integrator of the metabolic and stress response networks that are essential for pathogenicity and survival.

Importance: Understanding the regulatory mechanisms that govern virulence and environmental adaptation in Streptococcus mutans is essential for developing strategies to mitigate dental caries. This study reveals the critical role of the SMU.1147 gene in S. mutans in metabolic regulation, stress response, and cell viability. Our results demonstrate how the deletion of this gene affects sugar uptake and organic acid production, leading to imbalances in carbon metabolism and reduced long-term survival. These findings provide valuable insights into the ability of S. mutans to adapt to stressed conditions and highlight the role of SMU.1147 in modulating biofilm formation and virulence, contributing to our understanding of regulatory pathways in dental pathogens.