Decoding Adenine DNA Methylation Effects in <i>Streptococcus Mutans</i> : Insights Into Self‐DNA Protection and Autoaggregation

Streptococcus mutans, a key player in dental caries, faces multiple environmental challenges within the oral cavity, including oxidative stress, nutrient scarcity, and acidic pH. To survive and thrive, S. mutans has evolved intricate mechanisms, including the CSP-ComDE quorum sensing system, which coordinates responses to environmental cues. The CSP-ComDE system enables S. mutans to communicate with neighboring cells via its CSP pheromone. Under stress conditions, the CSP pheromone production increases, triggering a cascade of events. Notably, our research demonstrated that the CSP pheromone activates the expression of a Type II restriction-modification (R-M) system. Type II R-M systems are well-known tools in molecular biology and genetic engineering and consist of two distinct enzymes: a restriction enzyme and a methyltransferase. An increasing number of studies have revealed that bacterial adenine methylation (Dam methylation) has a broader role beyond mere DNA protection. In fact, the marks introduced into the DNA provide signals for a variety of physiological processes. Our results highlight a conserved chromosomal locus in S. mutans encoding the DpnII R-M system. DpnII R-M methylates DNA at 5'-GATC target sites within the S. mutans genome and cleaves unmarked DNA. Furthermore, our findings suggest that Dam methylation significantly impacts foreign DNA acquisition via natural transformation and modulates mutanobactin expression-a secondary metabolite linked to oxidative stress tolerance. Collectively, our findings suggest that Dam methylation bridges epigenetics and bacterial fitness, potentially opening new avenues in bacterial epigenetics. As we explore this intricate biological process, we may uncover novel therapeutic strategies to combat bacterial infections.