Two-Year Caries Clinical Study of the Efficacy of Novel Dentifrices Containing 1.5% Arginine, an Insoluble Calcium Compound and 1,450 ppm Fluoride

Kraivaphan, Petcharat; Amornchat, Cholticha; Triratana, Terdphong; Mateo, Luis R; Ellwood, R.P.; Cummins, D.; DeVizio, William; Zhang, Y.-P.

doi:10.1159/000353183

Cited by 94 publications

(97 citation statements)

References 13 publications

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“…Consistent with the microbiological data, 1.5% or 3% L-arginine treatments were equally effective in reducing both the biofilm biomass (dry weight) and the amount of insoluble EPS (versus vehicle control), while the biological effects of 0.75% L-arginine were modest. Based on these findings, we selected 1.5% L-arginine, which has also been shown to be a clinically effective concentration (29)(30)(31), for further analyses. Interestingly, the content of soluble EPS and intracellular polysaccharides (IPS) was unaffected (see Fig.…”

Section: Resultsmentioning

confidence: 99%

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l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

et al. 2016

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L-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous L-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, L-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous L-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) L-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical L-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, L-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H 2 O 2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H 2 O 2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of L-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor. IMPORTANCEDental caries is one of the most prevalent and costly infectious diseases worldwide, caused by a biofilm formed on tooth surfaces. Novel strategies that compromise the ability of virulent species to assemble and maintain pathogenic biofilms could be an effective alternative to conventional antimicrobials that indiscriminately kill other oral species, including commensal bacteria. L-Arginine at 1.5% has been shown to be clinically effective in modulating cariogenic biofilms via alkali production by arginolytic bacteria. Using a mixed-species ecological model, we show new mechanisms by which L-arginine disrupts the process of biofilm matrix assembly and the dynamic microbial interactions that are associated with cariogenic biofilm development, without impacting the bacterial viability. These results may aid in the development of enhanced methods to control biofilms using L-arginine. Biofilms formed on surfaces are highly organized and structured microbial communities enmeshed in an extracellular matrix composed of polymeric substances, such as exopoly...

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Section: Resultsmentioning

confidence: 99%

“…The available laboratory and clinical evidence supports exogenous L-arginine supplementation at the concentration of 1.5% (wt/vol) as a feasible adjunctive anticaries approach via ADS activity (28)(29)(30)(31). However, L-arginine may inflict additional changes in the biofilm milieu under conditions conducive to dental caries.…”

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confidence: 99%

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

et al. 2016

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“…An exogenous supply of arginine might activate the bacterial arginine deiminase system and counteract acid demineralization of tooth surface. In fact, a protective effect against caries of toothpaste containing arginine is considered, and its efficacy is suggested (1,16). Moreover, agmatine was produced by the addition of arginine (Fig.…”

Section: Metabolome Analysis Of Intracellular Metabolites During Aminmentioning

confidence: 99%

<b>Amino acid composition and amino acid-metabolic network in supragingival </b><b>plaque </b>

Washio¹,

Ogawa²,

Suzuki³

et al. 2016

Biomed. Res.

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Dental plaque metabolizes both carbohydrates and amino acids. The former can be degraded to acids mainly, while the latter can be degraded to various metabolites, including ammonia, acids and amines, and associated with acid-neutralization, oral malodor and tissue inflammation. However, amino acid metabolism in dental plaque is still unclear. This study aimed to elucidate what kinds of amino acids are available as metabolic substrates and how the amino acids are metabolized in supragingival plaque, by a metabolome analysis. Amino acids and the related metabolites in supragingival plaque were extracted and quantified comprehensively by CE-TOFMS. Plaque samples were also incubated with amino acids, and the amounts of ammonia and amino acid-related metabolites were measured. The concentration of glutamate was the highest in supragingival plaque, while the ammonia-production was the highest from glutamine. The obtained metabolome profile revealed that amino acids are degraded through various metabolic pathways, including deamination, decarboxylation and transamination and that these metabolic systems may link each other, as well as with carbohydrate metabolic pathways in dental plaque ecosystem. Moreover, glutamine and glutamate might be the main source of ammonia production, as well as arginine, and contribute to pH-homeostasis and counteraction to acid-induced demineralization in supragingival plaque.

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“…Results from studies also revealed that exposure to L-arginine altered biofilm ecology when bacteria were grown under cariogenic conditions, with the presence of 1.5% exogenous L-arginine favoring the growth of S. gordonii (commensal) over cariogenic S. mutans in an in vitro model (27). Large-scale randomized clinical trials also revealed that the use of 1.5% arginine in combination with 1,450 ppm fluoride in toothpaste provided better protection against the formation of new carious lesions and the progression of existing lesions and promoted remineralization better than a dentifrice with 1,450 ppm fluoride alone (28,29). Despite the accumulated evidence demonstrating the benefits of arginine on dental health, far less effort has been invested in exploring the potential effects of arginine on the growth and virulence of caries pathogens (24,27,30).…”

mentioning

confidence: 99%

Effects of Arginine on Streptococcus mutans Growth, Virulence Gene Expression, and Stress Tolerance

Chakraborty

Burne

2017

Appl Environ Microbiol

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Streptococcus mutans is a common constituent of oral biofilms and a primary etiologic agent of human dental caries. The bacteria associated with dental caries have potent abilities to produce organic acids from dietary carbohydrates and to grow and metabolize in acidic conditions. By contrast, many commensal bacteria produce ammonia through the arginine deiminase system (ADS), which moderates the pH of oral biofilms. Arginine metabolism by the ADS is a significant deterrent to the initiation and progression of dental caries. In this study, we observed how exogenously provided L-arginine affects the growth, the virulence properties, and the tolerance of environmental stresses of S. mutans. Supplementation with 1.5% arginine (final concentration) had an inhibitory effect on the growth of S. mutans in complex and chemically defined media, particularly when cells were exposed to acid or oxidative stress. The genes encoding virulence factors required for attachment/accumulation (gtfB and spaP), bacteriocins (nlmA, nlmB, nlmD, and cipB), and the sigma factor required for competence development (comX) were downregulated during growth with 1.5% arginine. Deep sequencing of RNA (RNA-Seq) comparing the transcriptomes of S. mutans growing in chemically defined media with and without 1.5% arginine revealed differential expression of genes encoding ATP-binding cassette transporters, metal transporters, and constituents required for survival, metabolism, and biofilm formation. Therefore, the mechanisms of action by which arginine inhibits dental caries include direct adverse effects on multiple virulence-related properties of the most common human dental caries pathogen.IMPORTANCE Metabolism of the amino acid arginine by the arginine deiminase system (ADS) of certain oral bacteria raises the pH of dental plaque and provides a selective advantage to health-associated bacteria, thereby protecting the host from dental caries (cavities). Here, we examine the effects of arginine on the cavitycausing bacterium Streptococcus mutans. We find that arginine negatively impacts the growth, the pathogenic potential, and the tolerance of environmental stresses in a way that is likely to compromise the ability of S. mutans to cause disease. Using genetic and genomic techniques, multiple mechanisms by which arginine exerts its influence on virulence-related properties of S. mutans are discovered. This report demonstrates that a primary mechanism of action by which arginine inhibits the initiation and progression of dental caries may be by reducing the pathogenic potential of S. mutans.

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Two-Year Caries Clinical Study of the Efficacy of Novel Dentifrices Containing 1.5% Arginine, an Insoluble Calcium Compound and 1,450 ppm Fluoride

Cited by 94 publications

References 13 publications

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

l -Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

<b>Amino acid composition and amino acid-metabolic network in supragingival </b><b>plaque </b>

Effects of Arginine on Streptococcus mutans Growth, Virulence Gene Expression, and Stress Tolerance

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