Extracellular Z-DNA Enhances Cariogenicity of Biofilm

Extracellular DNA (eDNA) is one of the core components of the extracellular matrix (ECM) in biofilms and provides attachment sites for microbes and other ECM components. However, little is known about the functions and underlying mechanisms of eDNA in the cariogenicity of dental plaque biofilms. A recent study demonstrated that conformational diversity of eDNA exists in biofilms, and the transition of eDNA from right-handed (B-DNA) to left-handed (Z-DNA) is associated with the structural stability and pathogenicity of biofilms. Caries-related biofilm is a complex multispecies microenvironment. The presence and biological function of the conformational transition of eDNA within this biofilm have not been previously reported. In this study, we found that extracellular Z-DNA is widely present in carious tissues and cariogenic biofilm, especially Streptococcus mutans, indicating its possible role in the occurrence and activity of dental caries. The content of extracellular Z-DNA showed species heterogeneity. The modulation of Z-DNA formation affected the level of extracellular polysaccharide. Increased formation of Z-DNA substantially strengthened the cariogenicity of the biofilm by increasing DNase resistance, structural density, and acid production. These insights provide a new perspective to understand the underlying function of the conformation transition of eDNA in promoting carious lesions, as well as a possible anti-biofilm strategy targeting extracellular Z-DNA.