Abstract
Fluoride is an inorganic monatomic anion that is widely used as an anti-cariogenic agent for the control of caries development. The aims of this study were to identify the mutated genes that give rise to fluoride-resistant (FR) strains of the cariogenic pathogen Streptococcus mutans and explore how genetic alterations in the genome of an S. mutans FR strain optimize the metabolism(s) implicated in the expression of virulence-associated traits. Here, we derived an S. mutans FR strain from a wild-type UA159 strain by continuous shifts to a medium supplemented with increasing concentrations of fluoride. The FR strain exhibited a slow growth rate and low yield under aerobic and oxidative stress conditions and was highly sensitive to acid stress. Notably, microscopy observation displayed morphological changes in which the FR strain had a slightly shorter cell length. Next, using the sequencing analyses, we found six mutations in the FR genome, which decreased the gene expression of the phosphoenolpyruvate-dependent phosphotransferase system (PTS). Indeed, the ability to intake carbohydrates was relatively reduced in the FR strain. Collectively, our results provide evidence that the genetic mutations in the genome of the FR strain modulate the expression of gene(s) for carbon metabolism(s) and cellular processes, leading to diminished fitness with respect to virulence and persistence.
Highlights
Dental caries is a common oral disease closely associated with the increasing intake of fermentable carbohydrates due to changes in food processes and dietary habits [1]
Considering the distinct characteristics of these resistant strains isolated from different experimental environments, we attempted to generate a new FR strain of S. mutans using the procedure described in the Methods section
Inparticular, particular, our ourresults resultshighlight highlight the theinterrelationship interrelationship of of aa reduced reduced ability ability to to uptake uptake carbohydrates carbohydrates and and aadecreased flux through glycolysis, which can have an abnormal influence on the biology decreased flux through glycolysis, which can have an abnormal influence on the biology of S. mutans
Summary
Dental caries is a common oral disease closely associated with the increasing intake of fermentable carbohydrates due to changes in food processes and dietary habits [1]. More than 700 species of microorganisms are present, of which Streptococcus mutans and Streptococcus sobrinus are dominantly isolated in dental caries [3,4,5]. S. mutans is one of the major agents responsible for the initiation of human dental caries, which forms dental plaque (dental biofilm) on the tooth surface. The acidic pH within the dental biofilm leads to an increased proportion of acid-tolerant microorganisms and promotes the occurrence and progression of caries [4,6]
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