Involvement of VicK in the acid tolerance of Streptococcus mutans

Background: Streptococcus mutans is a primary causative agent of dental caries. It utilizes dietary sucrose to produce lactic acid, which causes demineralization of the dental enamel leading to caries.  A key property conducive to the virulence of S. mutans, is its ability to induce an acid tolerance response (ATR) at pH values typical of that precluding caries lesions, which then affords protection from killing at lower sub-lethal pH values. This process requires that pH drops are detected so that necessary adaptive measures can be initiated using ATR. Objective: To investigate the involvement of the VicK sensor kinase in the ATR of S. mutans using DNA microarrays.  Methods: To compare expression profiles during ATR, we employed S. mutans UA159 wild-type strain and its VicK-deficient mutant (SmuvicK) derivative for DNA microarray analysis. Briefly, RNA was extracted from cultures grown to mid-log phase at pH 7.5, and consequently washed and exposed to either pH 7.5 or pH 5.5 for 1h.  After DNAse treatment and labelling, RNAs were used for cDNA synthesis and hybridized to microarrays slides, which were scanned and analysed. Results: Under low pH, the VicK regulon encompassed 115 transcripts representing genes that were differentially expressed (p<0.001). Of these, 43 and 72 transcripts were significantly up- and down-regulated relative to wild-type, respectively. Affected genes included those involved in stress responses, transport of sugars, osmoprotective functions, while a majority of genes had no predicted function. Notably, among pH-induced genes, 8 transcripts were only when VicK was present in the cell (i.e. wild-type), thus a strong VicK-mediated role in their regulation under low pH. Conclusions: Taken together, these findings expand the role of VicK as a putative pH sensor and support its involvement in the ATR of S. mutans. Acknowledgements: NIH Grant R01DE013230 and CIHR grant MT-15431.