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Natural products in caries research: current (limited) knowledge, challenges and future perspective.

Jeon JG, Rosalen PL, Falsetta ML, Koo H - Caries Res. (2011)

Bottom Line: Virulent biofilms firmly attached to tooth surfaces are prime biological factors associated with this disease.Furthermore, most of the studies have been focused on the general inhibitory effects on glucan synthesis as well as on bacterial metabolism and growth, often employing methods that do not address the pathophysiological aspects of the disease (e.g. bacteria in biofilms) and the length of exposure/retention in the mouth.This review focuses on gaps in the current knowledge and presents a model for investigating the use of natural products in anticaries chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Preventive Dentistry, BK 21 Program, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.

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Related in: MedlinePlus

Cariogenic biofilm formation (a–d) and potential targets (e) for disruption by natural products. a The Gtfs secreted by S. mutans are incorporated into pellicle (particularly GtfC) and adsorb on bacterial surfaces (mainly GtfB), including microorganisms that do not produce Gtfs (e.g. Actinomyces spp.). b Surface-adsorbed GtfB and GtfC rapidly utilize dietary sucrose (and starch hydrolysates) to synthesize insoluble and soluble glucans in situ; the soluble glucans formed by GtfD could serve as primers for GtfB enhancing overall synthesis of EPS. The Gtfs adsorbed onto enamel and microbial surfaces provide in situ an insoluble matrix for dental plaque-biofilm. Concomitantly, dietary carbohydrates (CHO) are metabolized into acids by acidogenic/aciduric organisms (e.g. S. mutans). c The glucan molecules provide avid binding sites on surfaces for S. mutans and other microorganisms mediating tight bacterial clustering and adherence to the tooth enamel (through glucan-glucan and glucan-Gbp interactions). Furthermore, Gtf-adsorbed bacteria de facto become glucan producers binding to tooth and microbial surfaces by the same mechanisms. This model could explain the rapid formation and accumulation of highly cohesive-adherent plaque in the presence of sucrose (and possibly starch) even if the number of S. mutans is relatively low. After the establishment of a glucan-rich biofilm matrix, ecological pressure (e.g. pH) will determine which bacteria may survive and dominate within plaque under frequent sucrose (or other fermentable carbohydrate) exposure. d If biofilm remains on tooth surfaces with frequent consumption of high-carbohydrate diet (especially sucrose), the amount of EPS and extent of acidification of the matrix will be increased. Such conditions cause biochemical, ecological and structural changes favoring the survival and dominance of highly acid stress-tolerant organisms in cohesive and firmly attached biofilms. The low-pH environment at the tooth-biofilm interface results in enhanced demineralization of enamel.
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Figure 1: Cariogenic biofilm formation (a–d) and potential targets (e) for disruption by natural products. a The Gtfs secreted by S. mutans are incorporated into pellicle (particularly GtfC) and adsorb on bacterial surfaces (mainly GtfB), including microorganisms that do not produce Gtfs (e.g. Actinomyces spp.). b Surface-adsorbed GtfB and GtfC rapidly utilize dietary sucrose (and starch hydrolysates) to synthesize insoluble and soluble glucans in situ; the soluble glucans formed by GtfD could serve as primers for GtfB enhancing overall synthesis of EPS. The Gtfs adsorbed onto enamel and microbial surfaces provide in situ an insoluble matrix for dental plaque-biofilm. Concomitantly, dietary carbohydrates (CHO) are metabolized into acids by acidogenic/aciduric organisms (e.g. S. mutans). c The glucan molecules provide avid binding sites on surfaces for S. mutans and other microorganisms mediating tight bacterial clustering and adherence to the tooth enamel (through glucan-glucan and glucan-Gbp interactions). Furthermore, Gtf-adsorbed bacteria de facto become glucan producers binding to tooth and microbial surfaces by the same mechanisms. This model could explain the rapid formation and accumulation of highly cohesive-adherent plaque in the presence of sucrose (and possibly starch) even if the number of S. mutans is relatively low. After the establishment of a glucan-rich biofilm matrix, ecological pressure (e.g. pH) will determine which bacteria may survive and dominate within plaque under frequent sucrose (or other fermentable carbohydrate) exposure. d If biofilm remains on tooth surfaces with frequent consumption of high-carbohydrate diet (especially sucrose), the amount of EPS and extent of acidification of the matrix will be increased. Such conditions cause biochemical, ecological and structural changes favoring the survival and dominance of highly acid stress-tolerant organisms in cohesive and firmly attached biofilms. The low-pH environment at the tooth-biofilm interface results in enhanced demineralization of enamel.

Mentions: Cariogenic biofilms develop following initial microbial attachment to and further accumulation on the tooth surface, which is predominantly mediated by sucrose-dependent mechanisms. The EPS is mainly comprised of glucans, which are synthesized by Gtfs present in saliva, in the acquired pellicle (primarily GtfC), and those adsorbed on bacterial surfaces (mostly GtfB) in the presence of sucrose. The glucans formed in situ provide (i) avid binding sites for colonization by S. mutans and other acidogenic/aciduric organisms, and (ii) a matrix that holds the microbial cells together to form structurally cohesive cell clusters known as microcolonies [Bowen and Koo, 2011] (fig. 1). If these biofilms are not removed from the tooth surface and are frequently exposed to dietary carbohydrates (especially sucrose), S. mutans (and other acidogenic and aciduric bacteria) within the biofilm community will metabolize sucrose to organic acids and synthesize polysaccharides in situ. The elevated amounts of EPS enhance bacterial adherence and biofilm cohesiveness, shelter matrix-encased bacteria from environmental assaults (e.g. antimicrobials), improve the stability of the structure and affect the diffusion properties of the biofilm matrix [Paes Leme et al., 2006; Bowen and Koo, 2011]. Furthermore, insoluble EPS provides a framework for the establishment of tightly adherent three-dimensional biofilm structures [Koo et al., 2010b]. Conversely, soluble glucans, fructans and intracellular polysaccharides serve as short-term storage compounds that can be metabolized to increase overall acid production. Acidification of the biofilm matrix affords a competitive ecological advantage to acid stress-tolerant and acidogenic flora, such as S. mutans [Quivey et al., 2000; Marsh, 2003; Lemos and Burne, 2008]. The low-pH environment subsequently created at the tooth-biofilm interface results in demineralization of the enamel. Clearly, exopolysaccharides, acidification of the biofilm matrix as well as acid tolerance mechanisms are critical for the development of cariogenic biofilms, and thus could be attractive and specific targets for precise and highly selective chemotherapeutic strategies.


Natural products in caries research: current (limited) knowledge, challenges and future perspective.

Jeon JG, Rosalen PL, Falsetta ML, Koo H - Caries Res. (2011)

Cariogenic biofilm formation (a–d) and potential targets (e) for disruption by natural products. a The Gtfs secreted by S. mutans are incorporated into pellicle (particularly GtfC) and adsorb on bacterial surfaces (mainly GtfB), including microorganisms that do not produce Gtfs (e.g. Actinomyces spp.). b Surface-adsorbed GtfB and GtfC rapidly utilize dietary sucrose (and starch hydrolysates) to synthesize insoluble and soluble glucans in situ; the soluble glucans formed by GtfD could serve as primers for GtfB enhancing overall synthesis of EPS. The Gtfs adsorbed onto enamel and microbial surfaces provide in situ an insoluble matrix for dental plaque-biofilm. Concomitantly, dietary carbohydrates (CHO) are metabolized into acids by acidogenic/aciduric organisms (e.g. S. mutans). c The glucan molecules provide avid binding sites on surfaces for S. mutans and other microorganisms mediating tight bacterial clustering and adherence to the tooth enamel (through glucan-glucan and glucan-Gbp interactions). Furthermore, Gtf-adsorbed bacteria de facto become glucan producers binding to tooth and microbial surfaces by the same mechanisms. This model could explain the rapid formation and accumulation of highly cohesive-adherent plaque in the presence of sucrose (and possibly starch) even if the number of S. mutans is relatively low. After the establishment of a glucan-rich biofilm matrix, ecological pressure (e.g. pH) will determine which bacteria may survive and dominate within plaque under frequent sucrose (or other fermentable carbohydrate) exposure. d If biofilm remains on tooth surfaces with frequent consumption of high-carbohydrate diet (especially sucrose), the amount of EPS and extent of acidification of the matrix will be increased. Such conditions cause biochemical, ecological and structural changes favoring the survival and dominance of highly acid stress-tolerant organisms in cohesive and firmly attached biofilms. The low-pH environment at the tooth-biofilm interface results in enhanced demineralization of enamel.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3104868&req=5

Figure 1: Cariogenic biofilm formation (a–d) and potential targets (e) for disruption by natural products. a The Gtfs secreted by S. mutans are incorporated into pellicle (particularly GtfC) and adsorb on bacterial surfaces (mainly GtfB), including microorganisms that do not produce Gtfs (e.g. Actinomyces spp.). b Surface-adsorbed GtfB and GtfC rapidly utilize dietary sucrose (and starch hydrolysates) to synthesize insoluble and soluble glucans in situ; the soluble glucans formed by GtfD could serve as primers for GtfB enhancing overall synthesis of EPS. The Gtfs adsorbed onto enamel and microbial surfaces provide in situ an insoluble matrix for dental plaque-biofilm. Concomitantly, dietary carbohydrates (CHO) are metabolized into acids by acidogenic/aciduric organisms (e.g. S. mutans). c The glucan molecules provide avid binding sites on surfaces for S. mutans and other microorganisms mediating tight bacterial clustering and adherence to the tooth enamel (through glucan-glucan and glucan-Gbp interactions). Furthermore, Gtf-adsorbed bacteria de facto become glucan producers binding to tooth and microbial surfaces by the same mechanisms. This model could explain the rapid formation and accumulation of highly cohesive-adherent plaque in the presence of sucrose (and possibly starch) even if the number of S. mutans is relatively low. After the establishment of a glucan-rich biofilm matrix, ecological pressure (e.g. pH) will determine which bacteria may survive and dominate within plaque under frequent sucrose (or other fermentable carbohydrate) exposure. d If biofilm remains on tooth surfaces with frequent consumption of high-carbohydrate diet (especially sucrose), the amount of EPS and extent of acidification of the matrix will be increased. Such conditions cause biochemical, ecological and structural changes favoring the survival and dominance of highly acid stress-tolerant organisms in cohesive and firmly attached biofilms. The low-pH environment at the tooth-biofilm interface results in enhanced demineralization of enamel.
Mentions: Cariogenic biofilms develop following initial microbial attachment to and further accumulation on the tooth surface, which is predominantly mediated by sucrose-dependent mechanisms. The EPS is mainly comprised of glucans, which are synthesized by Gtfs present in saliva, in the acquired pellicle (primarily GtfC), and those adsorbed on bacterial surfaces (mostly GtfB) in the presence of sucrose. The glucans formed in situ provide (i) avid binding sites for colonization by S. mutans and other acidogenic/aciduric organisms, and (ii) a matrix that holds the microbial cells together to form structurally cohesive cell clusters known as microcolonies [Bowen and Koo, 2011] (fig. 1). If these biofilms are not removed from the tooth surface and are frequently exposed to dietary carbohydrates (especially sucrose), S. mutans (and other acidogenic and aciduric bacteria) within the biofilm community will metabolize sucrose to organic acids and synthesize polysaccharides in situ. The elevated amounts of EPS enhance bacterial adherence and biofilm cohesiveness, shelter matrix-encased bacteria from environmental assaults (e.g. antimicrobials), improve the stability of the structure and affect the diffusion properties of the biofilm matrix [Paes Leme et al., 2006; Bowen and Koo, 2011]. Furthermore, insoluble EPS provides a framework for the establishment of tightly adherent three-dimensional biofilm structures [Koo et al., 2010b]. Conversely, soluble glucans, fructans and intracellular polysaccharides serve as short-term storage compounds that can be metabolized to increase overall acid production. Acidification of the biofilm matrix affords a competitive ecological advantage to acid stress-tolerant and acidogenic flora, such as S. mutans [Quivey et al., 2000; Marsh, 2003; Lemos and Burne, 2008]. The low-pH environment subsequently created at the tooth-biofilm interface results in demineralization of the enamel. Clearly, exopolysaccharides, acidification of the biofilm matrix as well as acid tolerance mechanisms are critical for the development of cariogenic biofilms, and thus could be attractive and specific targets for precise and highly selective chemotherapeutic strategies.

Bottom Line: Virulent biofilms firmly attached to tooth surfaces are prime biological factors associated with this disease.Furthermore, most of the studies have been focused on the general inhibitory effects on glucan synthesis as well as on bacterial metabolism and growth, often employing methods that do not address the pathophysiological aspects of the disease (e.g. bacteria in biofilms) and the length of exposure/retention in the mouth.This review focuses on gaps in the current knowledge and presents a model for investigating the use of natural products in anticaries chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Preventive Dentistry, BK 21 Program, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea.

Show MeSH
Related in: MedlinePlus