Abstract
The prolonged exposure of the cariogenic bacterial species Streptococcus mutans to high concentrations of fluoride leads to the development of fluoride resistance in this species. Previous studies confirmed the involvement of a mutation in a single chromosomal region in the occurrence of fluoride resistance. The involvement of multiple genomic mutations has not been verified. The aim of this study is to identify multiple genetic loci associated with fluoride resistance in S. mutans. The previously published whole genome sequences of two fluoride-resistant S. mutans strains (UA159-FR and C180-2FR) and their corresponding wild-type strains (UA159 and C180-2) were analyzed to locate shared chromosomal mutations in fluoride-resistant strains. Both fluoride-resistant strains were isolated in laboratory by culturing their mother strains in media with high concentrations of fluoride. The corresponding gene expression and enzyme activities were accordingly validated. Mutations were identified in two glycolytic enzymes, namely pyruvate kinase and enolase. Pyruvate kinase was deactivated in fluoride-resistant strain C180-2FR. Enolase was less inhibited by fluoride in fluoride-resistant strain UA159-FR than in its wild-type strain. Mutations in the promoter mutp constitutively increased the promoter activity and up-regulated the expression of the downstream fluoride antiporters in fluoride-resistant strains. Mutations in the intergenic region glpFp led to lower expression of glpF, encoding a glycerol uptake facilitator protein, in fluoride-resistant strains than in wild-type strains. Our results revealed that there is overlap of chromosomal regions with mutations among different fluoride-resistant S. mutans strains. They provide novel candidates for the study of the mechanisms of fluoride resistance.
Highlights
Fluoride has been applied for over 50 years as an effective anti-caries agent
S. mutans UA159-FR showed stronger fluoride resistance during growth when compared to S. mutans UA159
After comparing these single nucleotide polymorphisms (SNPs) with those found in S. mutans C180-2FR genome, we located three shared loci with mutations in both fluoride-resistant strains
Summary
Fluoride ions (F−) can prevent dental caries through their ability to protect dental hard tissue, as well as to inhibit bacterial growth and metabolism. Fluoride Resistance in S. mutans of cariogenic bacterial species, including Streptococcus mutans (Yoshihara et al, 2001). When present in bacterial cells, F− can directly or indirectly inhibit metabolic enzymes including enolase, F-ATPase and urease, leading to decreased growth and metabolism (Curran et al, 1994; Guha-Chowdhury et al, 1997; Burne and Marquis, 2000; van Loveren et al, 2008; Pandit et al, 2013). The results of our recent study indicated, that the biofilm fluoride-level may induce resistance in bacteria when the pH of the environment remains low for an extended period of time (Cai et al, 2017)
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