Regulation of oxidative response and extracellular polysaccharide synthesis by a diadenylate cyclase in Streptococcus...

Cyclic diadenosine monophosphate (c-di-AMP) has been implicated in the control of many important bacterial activities. However, the function of this molecule in Streptococcus mutans, the primary aetiological agent of human dental caries, is unknown. In this study, we identified and characterized a diadenylate cyclase, named CdaA, in S. mutans. Furthermore, we showed that in-frame deletion of the cdaA gene in S. mutans causes decreased c-di-AMP levels, increased sensitivity to hydrogen peroxide and increased production of extracellular polysaccharides. Global gene expression profiling revealed that more than 200 genes were significantly upregulated or downregulated (> 2.0-fold) in the cdaA mutant. Interestingly, genes with increased or decreased expression were clustered in cellular polysaccharide biosynthetic processes and oxidoreductase activity respectively. Notably, the expression of several genomic islands, such as GTF-B/C, TnSmu, CRISPR1-Cas and CRISPR2-Cas, was found to be altered in the cdaA mutant, indicating a possible link between these genomic islands and c-di-AMP signalling. Collectively, the results reported here show that CdaA is an important global modulator in S. mutans and is required for optimal growth and environmental adaption. This report also paves the way to unveil further the roles of c-di-AMP signalling networks in the biology and pathogenicity of S. mutans.