Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

Abstract

Streptococcus mutans in dental biofilms is regularly exposed to cycles of acidic pH during the ingestion of fermentable dietary carbohydrates. The ability of S. mutans to tolerate low pH is crucial for its virulence and pathogenesis in dental caries. To better understand its acid tolerance mechanisms, we performed genome-wide transcriptional analysis of S. mutans in response to an acidic pH signal. The preliminary results showed that adaptation of S. mutans to pH 5.5 induced differential expression of nearly 14 % of the genes in the genome, including 169 upregulated genes and 108 downregulated genes, largely categorized into nine functional groups. One of the most interesting findings was that the genes encoding multiple two-component systems (TCSs), including CiaHR, LevSR, LiaSR, ScnKR, Hk/Rr1037/1038 and ComDE, were upregulated during acid adaptation. Real-time qRT-PCR confirmed the same trend in the expression profiles of these genes at pH 5.5. To determine the roles of these transduction systems in acid adaptation, mutants with a deletion of the histidine-kinase-encoding genes were constructed and assayed for the acid tolerance response (ATR). The results revealed that inactivation of each of these systems resulted in a mutant that was impaired in ATR, since pre-exposure of these mutants to pH 5.5 did not induce the same level of protection against lethal pH levels as the parent did. A competitive fitness assay showed that all the mutants were unable to compete with the parent strain for persistence in dual-strain mixed cultures at acidic pH, although, with the exception of the mutant in liaS, little effect was observed at neutral pH. The evidence from this study suggests that the multiple TCSs are required for S. mutans to orchestrate its signal transduction networks for optimal adaptation to acidic pH.

Streptococcus mutans NADH Oxidase Lies at the Intersection of Overlapping Regulons Controlled by Oxygen and NAD + Levels

“…It is unclear whether differences observed between the ⌬nox strain and UA159 are directly due to the elevated oxygen concentration experienced by the ⌬nox strain or due to the loss of Nox functions other than oxygen reduction (such as regeneration of NAD ϩ ). Previously, changes in global transcription of S. mutans in response to acidic and oxygen stresses had been analyzed in cultures grown to exponential growth phase (58)(59)(60). Here, the tightly controlled environment of the chemostat was used to generate samples in which the external variables, such as nutrients, pH, and oxygen levels, could be rigorously regulated and adjusted.…”

Trk2 Potassium Transport System in Streptococcus mutans and Its Role in Potassium Homeostasis, Biofilm Formation, and Stress Tolerance

“…In addition to acid production, tolerance to low pH is an important determinant in maintaining glycolysis and surviving acidic environments, such as those found in carious lesions. A study conducted by Gong et al examined the acid-induced transcriptome of S. mutans and found that the expression of nearly 14% of the genes encoded in its genome was altered by acid stress (54). These included trkA, trkH, and trkB, all of which were significantly upregulated at low pH (54), suggesting their involvement in acid stress tolerance.…”

Stress Physiology of Lactic Acid Bacteria

“…Acetyl-CoA is rerouted toward the biosynthesis of fatty acids instead of butanoate (161,170), which may enhance the rigidity and impermeability of the cytoplasmic membrane (177,178). Changes in pyruvate metabolism were also observed in S. mutans under acid stress (166,167).…”

“…Under acid stress conditions, Lb. casei and S. mutans markedly decreased the synthesis of the phosphoenolpyruvate phosphotransferase system (PEP-PTS) for glucose, which is the primary carbohydrate transport system belonging to the PTS-GFL superfamily (165)(166)(167). Under the same conditions, an acid-resistant mutant of Lb.…”