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Background   Streptococcus salivarius  is an abundant isolate of the human oral microbiota. Since both pH and glucose availability fluctuate frequently in the oral cavity, the goal of this study was to investigate regulation by CodY, a conserved pleiotropic regulator of Gram positive bacteria, in response to these two signals. The chemostat culture system was employed to precisely control the growth parameters, and the transcriptomes of wild-type  S. salivarius  57.I and its CodY-null derivative (Δ codY ) grown at pH 7 and 5.5, with limited and excessive glucose supply were determined.    Results  The transcriptomic analysis revealed that CodY was most active at pH 7 under conditions of glucose limitation. Based on whether a CodY binding consensus could be located in the 5′ flanking region of the identified target, the transcriptomic analysis also found that CodY shaped the transcriptome via both direct and indirect regulation. Inactivation of  codY  reduced the glycolytic capacity and the viability of  S. salivarius  at pH 5.5 or in the presence of H 2 O 2 . Studies using the  Galleria mellonella  larva model showed that CodY was essential for the toxicity generated from  S. salivarius  infection, suggesting that CodY regulation was critical for immune evasion and systemic infections. Furthermore, the CodY-null mutant strain exhibited a clumping phenotype and reduced attachment in biofilm assays, suggesting that CodY also modulates cell wall metabolism. Finally, the expression of genes belonging to the CovR regulon was affected by  codY  inactivation, but CodY and CovR regulated these genes in opposite directions.    Conclusions  Metabolic adaptation in response to nutrient availability and growth pH is tightly linked to stress responses and virulence expression in  S. salivarius . The regulation of metabolism by CodY allows for the maximal utilization of available nutrients and ATP production. The counteractive regulation of the CovR regulon could fine tune the transcriptomes in response to environmental changes.    Electronic supplementary material  The online version of this article (10.1186/s12864-018-4781-z) contains supplementary material, which is available to authorized users.

Impact of growth pH and glucose concentrations on the CodY regulatory network in Streptococcus salivarius