Streptococcus mutans Cell Death: Novel Role for a Known Bacteriocin

Background: Programmed cell death (PCD) is a genetically regulated process of cell suicide that is well characterized in multi-cellular organisms. Recently, the existence of PCD has also been established in prokaryotes. Streptococcus mutans resides on the tooth surface as part of the dental biofilm, where it causes dissolution of tooth enamel through acid production. This bacterium employs a signal transduction system composed of the ComDE two-component regulatory system and its secreted pheromone CSP to control the expression of virulence factors. Recently, it has been shown that CSP can also induce a PCD-like process in S. mutans. Objective: To characterize the genetic pathways involved in CSP-induced cell death in S. mutans, and investigate its biological significance. Methods: We performed growth kinetics experiments under high concentrations of synthetic CSP to determine the kinetics and physiology of cell death. A DNA microarray experiment was also designed to identify the genes activated during the killing process. Results: By combining cell physiology, gene expression analysis and mutagenesis, we have identified a CSP-induced bacteriocin-like peptide, CipB, and its cognate immunity protein, CipC, involved in S. mutans cell death. Results from co-cultivation cell viability assays and experiments conducted with purified recombinant CipB (full-length and truncated forms) suggested that CipB acts intracellularly to cause cell death. Moreover, our results suggested that CipB may also play a role in the uptake of extracellular DNA released during the lysis of sibling cells. Conclusions: The CSP-induced cell death pathway in S. mutans involves the CipB bacteriocin and its CipC immunity factor. The CSP-induced cell death pathway may provide us with new targets for antibacterial therapies designed to treat biofilm-related infections. Supported by NIDCR grant DE013230