Anti-cariogenic Characteristics of Rubusoside

Kim, Jeesoo; Nguyen, Thi Thanh Hanh; Jin, Juhui; Septiana, Iis; Son, Gyu Min; Lee, Gang Hee; Jung, You Jin; Qureshi, Dilshad; Mok, Il Kyoon; Pal, Kunal; Yang, Soo Yeon; Kim, Seong Bo; Kim, Doman

doi:10.1007/s12257-018-0408-0

Cited by 17 publications

(9 citation statements)

References 23 publications

(34 reference statements)

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“…The effect of rubusoside on related proteins is due to the disruption of the spatial conformation of the protein. A recent study suggested that rubusoside may inhibit the mutansucrase activity of S. mutans by influencing hydrophobic and hydrogen bond (H bond) interactions between rubusoside and the amino acid residues at the active-site pocket of mutansucrase (47). More studies of S. mutans are needed, and the quantitative PCR results need to be confirmed at the protein level to verify the current results.…”

Section: Discussionmentioning

confidence: 83%

Effect of Rubusoside, a Natural Sucrose Substitute, on Streptococcus mutans Biofilm Cariogenic Potential and Virulence Gene Expression In Vitro

Guan

Che

Zhou

et al. 2020

Appl Environ Microbiol

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Dental caries is a biofilm-mediated disease with Streptococcus mutans as the main pathogenic microorganism, and its incidence is closely related to sucrose. Rubusoside is a natural non-nutritive sweetener isolated from Rubus suavissimu S.Lee. This study was designed to determine the effect of the sucrose substitute on cariogenic properties and virulence gene expression of S. mutans biofilms. S. mutans was exposed to: BHI medium (as a control), BHI+1% sucrose, BHI+1% rubusoside, and BHI +1% xylitol. The growth curve of biofilm was monitored with crystal violet staining and pH was measured every 24 h. After 5 days, the biofilms formed on the glass coverslips were recovered to determine the biomass (dry weight and total soluble proteins), colony-forming units, and intra- and extracellular polysaccharides. Biofilm structural imaging was observed using a scanning electron microscope (SEM). The virulence gene expression (gtfB, gtfC, gtfD, ftf, spaP, gbpB, ldh, atpF, vicR, and comD) was determined by rt-qPCR. Compared to growth in sucrose, xylitol and control, growth in rubusoside resulted in a lower acid production, while also reducing the biofilm accumulation, bacterial viability, and even reducing the production of extracellular polysaccharides. And less biofilm formation and extracellular matrix was observed through SEM in rubusoside than sucrose and xylitol. From the perspective of virulence genes, rubusoside and xylitol significantly inhibited expression of virulence genes compared with sucrose, among which, down-regulation of the gtfB, gtfC, gbpB, ldh, and comD was found in rubusoside than xylitol. Therefore, rubusoside appears to be less potential cariogenicity than sucrose and xylitol, and may become an effective sucrose substitute for caries prevention. Further studies need to deepen these findings. Importance Dental caries, as a major public health challenge, places a heavy biological, social and financial burden on individuals and health care systems. To palliate the deleterious effect of sucrose on the virulence factors of S. mutans, massive commercial products have oriented towards developing sucrose substitutes. Rubusoside, a natural sucrose substitute, is a plant extract with high sweetness. Although some studies have shown that rubusoside do not produce acids and inhibit the growth of S. mutans, little attention has been paid to dental biofilm and underlying mechanisms. Our study focuses on the effect of rubusoside on formation and structure of biofilm, and expression of virulence genes. Results confirms that rubusoside can inhibit accumulation, bacterial viability, polysaccharide production of biofilm, and inhibit related gene expression. These results provide further insight into the cariogenicity of S. mutans biofilm, and demonstrate a new perspective for studying the impact of sucrose substitutes on caries.

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Section: Discussionmentioning

confidence: 83%

Effect of Rubusoside, a Natural Sucrose Substitute, on Streptococcus mutans Biofilm Cariogenic Potential and Virulence Gene Expression In Vitro

Guan

Che

Zhou

et al. 2020

Appl Environ Microbiol

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“…Alternatively, hyaluronic acid can be produced by microbial fermentation using Streptococcus species. For a long time, industrial-scale production of hyaluronic acid has been performed using a pathogen Streptococcus zooepidemicus (Kim et al, 1996; Schiraldi et al, 2010), which produces a pathogenic factor together hyaluronic acid that contributes to forming the extracellular capsule (Kim et al, 2019). Because of this risk, there has been increasing interest in engineering of non-pathogenic microorganisms, including genus of Escherichia, Bacillus, Lactococcus , and Agrobacterium , for hyaluronic acid production (Widner et al, 2005; Chien and Lee, 2007; Mao and Chen, 2007; Yu and Stephanopoulos, 2008).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Engineering of Escherichia coli for the Production of Hyaluronic Acid From Glucose and Galactose

Woo

Seong

Lee

et al. 2019

Front. Bioeng. Biotechnol.

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Hyaluronic acid is a glycosaminoglycan biopolymer widely present throughout connective and epithelial tissue, and has been of great interest for medical and cosmetic applications. In the microbial production of hyaluronic acid, it has not been established to utilize galactose enabling to be converted to UDP-glucuronic acid, which is a precursor for hyaluronic acid biosynthesis. In this study, we engineered Escherichia coli to produce hyaluronic acid from glucose and galactose. The galactose-utilizing Leloir pathway was activated by knocking out the galR and galS genes encoding the transcriptional repressors. Also, the hasA gene from Streptococcus zooepidemicus was introduced for the expression of hyaluronic acid synthase. The consumption rates of glucose and galactose were modulated by knockout of the pfkA and zwf genes, which encode 6-phosphofructokinase I and glucose-6-phosphate dehydrogenase, respectively. Furthermore, the precursor biosynthesis pathway for hyaluronic acid production was manipulated by separately overexpressing the gene clusters galU-ugd and glmS-glmM-glmU, which enable the production of UDP-glucuronic acid and UDP-N-acetyl-glucosamine, respectively. Batch culture of the final engineered strain produced 29.98 mg/L of hyaluronic acid from glucose and galactose. As a proof of concept, this study demonstrated the production of hyaluronic acid from glucose and galactose in the engineered E. coli.

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“…In addition, Lengsfeld et al demonstrated that berryderived polysaccharides can combat H. pylori infection in vivo by preventing bacterial binding to the gastric mucosa [53]. Additional studies have shown antibacterial effects for berry-derived sanguiin H-6 [35] and rubusoside [54]. Further experiments are needed to identify the raspberry and blackberry compounds that mediate antimicrobial activity against H. pylori.…”

Section: Discussionmentioning

confidence: 99%

A High-Throughput Metabolic Microarray Assay Reveals Antibacterial Effects of Black and Red Raspberries and Blackberries against Helicobacter pylori Infection

et al. 2021

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Helicobacter pylori infection is commonly treated with a combination of antibiotics and proton pump inhibitors. However, since H. pylori is becoming increasingly resistant to standard antibiotic regimens, novel treatment strategies are needed. Previous studies have demonstrated that black and red berries may have antibacterial properties. Therefore, we analyzed the antibacterial effects of black and red raspberries and blackberries on H. pylori. Freeze-dried powders and organic extracts from black and red raspberries and blackberries were prepared, and high-performance liquid chromatography was used to measure the concentrations of anthocyanins, which are considered the major active ingredients. To monitor antibiotic effects of the berry preparations on H. pylori, a high-throughput metabolic growth assay based on the Biolog system was developed and validated with the antibiotic metronidazole. Biocompatibility was analyzed using human gastric organoids. All berry preparations tested had significant bactericidal effects in vitro, with MIC90 values ranging from 0.49 to 4.17%. Antimicrobial activity was higher for extracts than powders and appeared to be independent of the anthocyanin concentration. Importantly, human gastric epithelial cell viability was not negatively impacted by black raspberry extract applied at the concentration required for complete bacterial growth inhibition. Our data suggest that black and red raspberry and blackberry extracts may have potential applications in the treatment and prevention of H. pylori infection but differ widely in their MICs. Moreover, we demonstrate that the Biolog metabolic assay is suitable for high-throughput antimicrobial susceptibility screening of H. pylori.

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Anti-cariogenic Characteristics of Rubusoside

Cited by 17 publications

References 23 publications

Effect of Rubusoside, a Natural Sucrose Substitute, on Streptococcus mutans Biofilm Cariogenic Potential and Virulence Gene Expression In Vitro

Effect of Rubusoside, a Natural Sucrose Substitute, on Streptococcus mutans Biofilm Cariogenic Potential and Virulence Gene Expression In Vitro

Metabolic Engineering of Escherichia coli for the Production of Hyaluronic Acid From Glucose and Galactose

A High-Throughput Metabolic Microarray Assay Reveals Antibacterial Effects of Black and Red Raspberries and Blackberries against Helicobacter pylori Infection

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