Effect of Copper Applied Topically or in Drinking Water on Experimental Caries in Rats

Afseth, John; Amsbaugh, S.M.; Monell-Torrens, E.; Bowen, William H.; Rölla, Gunnar; Brunelle, Janet A.; Dahl, Erik

doi:10.1159/000260799

Cited by 25 publications

(27 citation statements)

References 5 publications

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“…Incorporation of 320 ppm Cu in sucrose resulted in less smooth-surface caries in rats compared to a sucroseonly control group [Rosalen et al, 1996b]. Afseth et al [1984] observed that 65 ppm Cu in drinking water significantly reduced caries and the number of S. mutans on tooth surfaces in rats. These concentrations of 65-320 ppm copper are generally higher than those found in the present study to inhibit bacterial growth (0-4.5 ppm).…”

Section: Correlations Of Ions and Relative Bacterial Growth Ratesmentioning

confidence: 91%

Ion Release from Copper Phosphate Cement and Influence on <i>Streptococcus mutans</i> Growth in vitro: A Comparative Study

Foley

Blackwell

2003

Caries Res

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The aim of this study was to compare the effects of a black copper cement (BCC), an established restorative material (a conventional glass ionomer cement) and two temporary restorative materials (a zinc phosphate and a zinc polycarboxylate cement) on the growth of Streptococcus mutans in vitro, and to correlate bacterial growth with ion release from each material. Test specimens were eluted in either 0.1 M lactic acid, pH 4, or 0.1 M sodium chloride, pH 7. At 2 days, 7 days, 28 days and 6 months, eluates were inoculated with S. mutans and bacterial growth was recorded. Metal ion (Cu²⁺, Zn²⁺and Mg²⁺) and fluoride release were measured. At most immersion times, the different materials had a statistically significant inhibitory effect on bacterial growth compared to the respective control, at both pH levels. The inhibitory effect decreased with time and in most cases was associated with high levels of ion release at the beginning of the experimental period, followed by significantly lower levels. For BCC, there were statistically significant relationships between the median rates of growth of S. mutans in the presence of BCC eluates and the median values for release of copper and zinc, although not magnesium. Of the different materials, BCC demonstrated greatest antibacterial activity.

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Section: Correlations Of Ions and Relative Bacterial Growth Ratesmentioning

confidence: 91%

Ion Release from Copper Phosphate Cement and Influence on <i>Streptococcus mutans</i> Growth in vitro: A Comparative Study

Foley

Blackwell

2003

Caries Res

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“…Numerous studies have indicated the inhibitory effects of copper on S. mutans growth and caries formation (15)(16)(17)(18)(19)(20)(21)(22). The copper concentrations in saliva and dental plaque vary between individuals and depend on the age, sex, nutrient intake, etc.…”

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confidence: 99%

The copYAZ Operon Functions in Copper Efflux, Biofilm Formation, Genetic Transformation, and Stress Tolerance in Streptococcus mutans

et al. 2015

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In bacteria, copper homeostasis is closely monitored to ensure proper cellular functions while avoiding cell damage. Most Gram-positive bacteria utilize the copYABZ operon for copper homeostasis, where copA and copB encode copper-transporting P-type ATPases, whereas copY and copZ regulate the expression of the cop operon. Streptococcus mutans is a biofilm-forming oral pathogen that harbors a putative copper-transporting copYAZ operon. Here, we characterized the role of copYAZ operon in the physiology of S. mutans and delineated the mechanisms of copper-induced toxicity in this bacterium. We observed that copper induced toxicity in S. mutans cells by generating oxidative stress and disrupting their membrane potential. Deletion of the copYAZ operon in S. mutans strain UA159 resulted in reduced cell viability under copper, acid, and oxidative stress relative to the viability of the wild type under these conditions. Furthermore, the ability of S. mutans to form biofilms and develop genetic competence was impaired under copper stress. Briefly, copper stress significantly reduced cell adherence and total biofilm biomass, concomitantly repressing the transcription of the gtfB, gtfC, gtfD, gbpB, and gbpC genes, whose products have roles in maintaining the structural and/or functional integrity of the S. mutans biofilm. Furthermore, supplementation with copper or loss of copYAZ resulted in significant reductions in transformability and in the transcription of competence-associated genes. Copper transport assays revealed that the ⌬copYAZ strain accrued significantly large amounts of intracellular copper compared with the amount of copper accumulation in the wild-type strain, thereby demonstrating a role for CopYAZ in the copper efflux of S. mutans. The complementation of the CopYAZ system restored copper expulsion, membrane potential, and stress tolerance in the copYAZ-null mutant. Taking these results collectively, we have established the function of the S. mutans CopYAZ system in copper export and have further expanded knowledge on the importance of copper homeostasis and the CopYAZ system in modulating streptococcal physiology, including stress tolerance, membrane potential, genetic competence, and biofilm formation. IMPORTANCE S. mutans is best known for its role in the initiation and progression of human dental caries, one of the most common chronic diseases worldwide. S. mutans is also implicated in bacterial endocarditis, a life-threatening inflammation of the heart valve. The core virulence factors of S. mutans include its ability to produce and sustain acidic conditions and to form a polysaccharide-encased biofilm that provides protection against environmental insults. Here, we demonstrate that the addition of copper and/or deletion of copYAZ (the copper homeostasis system) have serious implications in modulating biofilm formation, stress tolerance, and genetic transformation in S. mutans. Manipulating the pathways affected by copper and the copYAZ system may help to develop potential therapeutics to prev...

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“…A number of early reports, however, suggest that copper cements are bactericidal [Smirnow, 1915] and it has been postulated that this effect is due to copper ion release. Copper ions are known to have a proven antibacterial and hence antiplaque effect, both in vitro on selected oral bacteria [Duguid, 1983;Morrier et al, 1998] and in vivo [Afseth, 1983;Afseth et al, 1980Afseth et al, , 1988, as well as anticaries activity in animal models [Afseth et al, 1984;Rosalen et al, 1996]. Given this background, the aims of this clinical trial were firstly, to determine the effect of a copper phosphate cement and a conventional glass ionomer on the bacteriological composition of carious dentine sealed under such restorations in vivo.…”

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confidence: 99%

In vivo Cariostatic Effect of Black Copper Cement on Carious Dentine

Foley

Blackwell²

2003

Caries Res

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This study compared the effect of a copper phosphate cement (BCC) and a conventional glass ionomer cement (GIC) on carious dentine that remains under restorations in vivo. Using a split-mouth design, 45 primary molar pairs with dentine caries were sampled microbiologically. Without further removal of carious dentine, the molar pairs were randomly allocated to three restorative groups: (1) one cavity was lined with BCC and restored with GIC and the other was kept under review as an untreated control; (2) one cavity was restored with GIC, whilst the other was kept under review; (3) one cavity was lined with BCC and restored with GIC, whilst the other was filled with GIC. The dentine was re-sampled microbiologically at 1 month (30 pairs) and 6 months (15 pairs). BCC demonstrated a significant effect on the total anaerobic count over 1 month, when paired with both the control and GIC, whereas the antibacterial effects of GIC compared with no treatment were not statistically significant. In addition, BCC performed significantly better than no treatment in reducing mutans streptococci and lactobacilli over 1 month. Over 6 months, BCC caused a significantly greater reduction in mutans streptococci than GIC. In conclusion, BCC demonstrated a significant antibacterial effect on carious dentine in vivo.

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Effect of Copper Applied Topically or in Drinking Water on Experimental Caries in Rats

Cited by 25 publications

References 5 publications

Ion Release from Copper Phosphate Cement and Influence on <i>Streptococcus mutans</i> Growth in vitro: A Comparative Study

Ion Release from Copper Phosphate Cement and Influence on <i>Streptococcus mutans</i> Growth in vitro: A Comparative Study

The copYAZ Operon Functions in Copper Efflux, Biofilm Formation, Genetic Transformation, and Stress Tolerance in Streptococcus mutans

In vivo Cariostatic Effect of Black Copper Cement on Carious Dentine

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