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Volume 24, No. 3

Biological methods of dental caries prevention. A review A. H. Rogers, M.Sc.(Adel.), Ph.D.(Leeds), M.A.S.M. Senior Lecturer in Microbiology, The University of Adelaide

ABSTRACT-Anumber of measures by which tooth resistance could be increased or by which potentially cariogenic bacteria could be eliminated or their deleterious effects minimized are discussed. Many of them have proved valuable at the individual patient level but cannot be applied as a public health measure.

(Received for publication November, 1978)

Introduction Of the procedures shown to have some effect in the prevention of dental caries only fluoridation has been implemented as a public health measure and, since caries is rarely if ever a life-threatening disease, research should be directed at measures that require little or no co-operation on the part of the individual. Broadly speaking, preventive measures are aimed at increasing the tooth resistance ;decreasing the cariogenic potential of food; eliminating potentially cariogenic bacteria or reducing their deleterious activities. Increasing tooth resistance Trace elements The effects of fluoride are well-known and the mechanisms by which it exerts its cariostasis have recently been reviewed in detail.’ One important aspect involves interference with the microbial metabolism of carbohydrates.z Despite the fact that sensitive analytical methods for measuring other trace elements have only recently become a ~ a i l a b l e ,it~ does appear that higher concentrations in drinking water of elements such as molybdenum, strontium, boron, lithium and vanadium

can be correlated with lower caries pre~alence.~ In contrast, elements such as selenium, cadmium and lead appear to be caries-pr~moting.~ However, much of this work ignores the fact that most trace elements are obtained from food and not from drinking water. Apart from the studies of Schamschula and cow o r k e r ~ , ~ ,there is little information on the trace element content of dental plaque. In comparing New Guineans with a group of Australian school children, these authors observed that plaque from the latter group showed higher levels of lead and copper while the former had higher levels of lithium and a considerably higher calcium/strontium ratio.3 The role of magnesium in plaque warrants further investigation in view of the fact that, in the presence of phosphate, it has a marked effect on cariogenesis and is also one of the first elements removed in early enamel caries.6 Moreover, it has recently been shown that among the four biochemical differences in plaques from two areas differing markedly in caries levels was the significantly higher level of magnesium in the samples from the low-caries area.’

’ Brown, *



W. E., and Konig, K. G. (Edit.)-Cariostatic mechanisms of fluorides. Caries Res., 1 I : suppl. I, 1-327, 1971. Cole, J. A.--A biochemical approach to the control of dental caries. Biochem. SOC.Trans., 5 : 4, 1232-1239, 1977. Schamschula, R. G., Agus, H.,Bunzel, M., Adkins, 9. L., and Barmes, D. E.-The concentrations of selected major and trace minerals in human dental plaque. Archs. Oral Biol., 22: 5 , 321-325 (May) 1977.



Navia, J. M.-Prevention of dental caries: Agents which increase tooth resistance to dental caries. Int. Dent. J., 22: 4, 427440 (Dec.) 1972. Schamschula, R. G., Adkins. B. L., Barmes, D. E., Charlton, G., and Davey, B. G.-Caries experience and the mineral content of plaque in a primitive population in New Guinea. J. Dent. Res., 56: sp. issue C, 62-70 (Oct.) 1977. Bowen, W. H.-Nature of plaque. Oral Sciences Revs., 9 : 3-21, 1976. Bowen, W. H., Velez, H., Aguila, M., Velasquez, H., Sierra, L. I., and Gillespie, G.-Themicrobiology and biochemistry of plaque, saliva, and drinking water from two communities with contrasting levels of caries in Colombia, S.A. J. Dent. Res., 56: sp. issue C , 32-39 (Oct.) 1977.

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In the same study,' an inverse relationship between the hardness of water and levels of caries was also found. It was suggested that such an increased level of ions might act to desorb (leach out) protein from hydroxyapatite and thus account for the decreased levels of plaque in the subjects with lower levels of caries. Indeed, recent work8 indicates that polyvalent cations such as tin, aluminium, zinc, and magnesium, reduce plaque function in vivo. Other elements One of the most critical questions in caries research concerns the factors in plaque which influence its cariogenicity. One relevant observation is that a high calcium content and calcium/phosphorus ratio in plaque are both associated with relative freedom from cariess, Another is the finding that the fasting plaque pH is higher in caries-resistant than in caries-prone areas of the mouth.1° Therefore it has been suggested" that a combination of the calcium and phosphate content of plaque and of the range of pH changes, both under the influence of saliva, are related to the cariogenicity of plaque. The cariostatic role of the two major elements, calcium and phosphorus, has been well documented. l 2 The general area of trace and other elements in relation to caries has been confused by inconclusive and conflicting reportsLz and much carefully planned and executed research is needed before application of any element could be expected to achieve the public health benefit gained from fluoride. Of particular value would be research into the factors that govern the availability of elements in p l a q ~ e . ~ Occlusal sealants The use of self-polymerizing or ultraviolet light polymerizing compounds in preventing caries in pits and fissuresi3 is mentioned here because it has biological overtones in the sense that such materials prevent colonization by potentially cariogenic bacteria. For optimal protection these surfaces should be sealed soon after tooth eruption-the most caries-susceptible time-

Skjorland, K., Gjermo, P., and Rolla, G.-Effect of some polyvalent cations on plaque formation in vivo. Scand. J. Dent. Clin. Nth. Amer., 20: 3. 491-505 (July) 1976. " Dawes, C., and Jenkins, G. N.-Some inorganic constituents of dental plaque and their relationship to early calculus formation and caries. Archs. Oral Biol., 7: 2, 161-172 (Mar.-Apr.) 1962. I " Kleinberg. I., and Jenkins, G. N.-The pH of dental plaque in the different areas of the mouth before and after meals and their relationship to the pH and rate of flow of resting saliva. Archs. Oral Biol., 9: 5, 493-516 (Sept.-Oct.) 1964. I I Jenkins, G. N.-The physiology and biochemistry of the mouth. Oxford, Blackwell Scientific Publications, 4th ed., 1978 (p. 397). I 2 Kreitzman, S. N.-Nutrition in the process of dental caries. Dent. Clin. Nth. Amer., 20: 3, 491-505 (July) 1976. Buonocore, M.-Adhesive sealing of pits and fissures for caries prevention, with use of ultraviolet light. J.A.D.A., 80: 2, 324328 (Feb.) 1970.

but problems of retention exist and the sealant may have to be replaced periodically. Decreasing the cariogenicity of foods The classic Vipeholm study14 showed the importance of amount, form and frequency of ingestion of sucrose in relation to caries incidence. Much subsequent epidemiological and experimental evidence confirmed this finding, and supportive evidence cbmes from subjects with hereditary fructose intolerance. A high proportion of such people, who avoid eating sucrose-containing foods, are caries-free.' 5 . l 6 Animal tests, in which the cariogenicity of different sugars has been investigated, have yielded somewhat conflicting results due to differences in the test animal strains, test diets and microbial flora used." Most of these experiments involved the use of rodents but recent work with monkeys has shown a mixture of glucose and fructose to be no less cariogenic than sucrose. However, sucrose appears to be consistently more caries-conducive than other sugars and palatable substitutes that can be safely used as sweetening agents should be ~ 0 u g h t . l ~ Sugar substitutes Available and potential sweetening agents have been reviewedz0,z 1 but few have been tested for their cariostatic effects in animals or their effect on human plaque and its pH; still fewer have been tested to determine cariostatic effects in humans. The polyols-sorbitol, mannitol and xylitol-as well as starch hydrolysates are among compounds that have been investigated. Using an intra-oral cariogenicity test, i t was found that mannitol and sorbitol were Gustafsson, B. E., Quensel, C. E.. Ludqvist, C., Grahnen. H.. Bonow, B. E., and Krasse. B.-The Vipeholm dental caries study. The effect of different levels of carbohydrate intake on caries activity in 436 individuals observed for five years. Acta Odontol. Scand., I 1 : 232-364, 1954. l 5 Newbrun, E.-Sucrose, the arch criminal of dental caries. Odontol. Revy, 18: 4. 373-386, 1967. l 6 Marthaler. 'T-Epidemiological and clinical dental findings in relation to intake of carbohydrates. Caries Res.. 1 : 222-238, 1967. I ' MLkinen, K. K.-The role of sucrose and other sugars in the development of dental caries: A review. lnt. Dent. J., 22: 3, 363-386 (Sept.) 1972. Colman. G.. Bowen, W. H., and Cole, M. F.-The effects of sucrose, fructose, and a mixture of glucose and fructose on the incidence of dental caries in monkeys (M. fascicularis). Brit. Dent. J., 142: 217-221 (Apr.) 1977. l 9 Newbrun, E., and Frostell, G.-Sugar restriction and substitution for caries prevention. Caries Res., 12: suppl. I , 65-73, 1978. 2 o Shaw, J. H., and Roussos, G. G. (Edits.)-Sweeteners and dental caries, suppl. : Feeding-weight and obesity abstracts, Information Retrieval In&, Washington D.C., U S A . , 1978. 2 1 Morris, J. A,-Sweetening agents from natural sources. Lloydia, 39: 25-38, 1976. 2 z Koulourides, T., Bodden, R., Keller, S., Manson-Hing, L.. Lastra, J., and Housch. T.-Cariogenicity of nine sugars tested with an intraoral device in man. Caries Res., 10: 427441, 1976. l4

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Australian Dental Journal, June, 1979 significantly less cariogenic than sucrose, glucose or fructose.z7 Sorbitol also caused a significant reduction in both plaque accumulation and caries in experimental rodentsz3and, following a mouthrinse, produced significantly less pH change in human plaque than any of the other sugars tested.z4

Lycasin is a hydrogenated starch hydrolysate consisting of a mixture of polyols such as sorbitol and maltitol. Developed in Sweden, it has been used in sweets but clinical trials were inconclusive because the young children participating in the study also consumed some sucrose from other food sources.z5It was, however, significantly less cariogenic than sucrose in the rodent test systemz3 and produced less change in pH in human plaque following a mouthrinse with a ten per cent solution.z4 Xylitol. Of all the sugar substitutes, xylitol has perhaps been the most extensively studied.lg. 2 6 It was found to be of very low cariogenicity in ratsz7and non-cariogenic in the human intra-oral cariogenicity testz2 In Turku, Finland, an extensive human clinical trial was mounted with the aim of evaluating the differences in caries incidence as influenced by sucrose, fructose, and xylitol consumption.z8 The group consuming fructose-containing products showed less caries than the sucrose group but it was of questionable significance. On the other hand, after only one year, the xylitol group showed ninety per cent less caries than the sucrose group-a highly significant reduction. The xylitol group also showed a reduction in both the amount of plaque formed and the Streptococcus mutans counts. Of importance was the additional finding that there was no adaptation of the oral flora to utilization of xylitol for acid production. Xylitol-containing chewing gums are commercially available in a number of countriesz9 but it is doubtful whether xylitol could be considered as a total dietary substitute for sucrose at the present time because of both its high cost and the possible gastro23

24

26

27

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Frostell, G .-The caries-inducing properties of LycasinD in comparison to sucrose. Dt. zahnazrtl. Ztg., 26: 1181-1 187, 1971. Frostell, G.-Effects of mouthrinses with sucrose, glucose, fructose, lactose, sorbitol, and Lycasin@) on the pH of dental plaque. Odont. Revy, 24: 217-226, 1973. Frostell, G . ,Blomlof, L., Blomqvist, T., Dahl, G. M., Edward, S., Fjellstrom, A., Henrikson, C. 0..Large, O., Nord, C. E., and Nordenwall, K. J.-Substitution of sucrose by Lycasinm in candy, “The Roslagen study”. Acta Odontol. Scand., 32: 235-254, 1974. Makinen, K. K.-Microbial growth and metabolism in plaque in the presence of sugar alcohols. In, Proc. Microbial aspects of dental caries. Stiles, H. M. et al., (Edits.), Sp. Suppl. Microbiol. Abstrs., pp. 521-538, 1976. Miihlemann, H. R., Schmid, R., Noguchi, T., Imfeld, T., and Hirsch, R. S.-Some dental effects of xylitol under laboratory and in vivo conditions. Caries Res., I1 : 263-276, 1977. Scheinin, A,, and Makinen, K. K.-Turku sugar studies I-IV. Acta Odontol. Scand., 32: 383444, 1974. Scheinin, A,, Makinen, K. K., Tammisalo, E., and Rekola, M.-Incidence of dental caries in relation to 1-year consumption of xylitol chewing gum. Acta Odontoi. Scand.. 33: 269-278, 1975.

intestinal side-effects it may produce when taken in large amounts.28 Coupling sugars. Another recent development is that of coupling sugars,30 which are produced by the incubation of starch and sucrose with a microbial glucosyltransferase. One such preparation, rendered sucrose-free, and containing glucose, fructose, maltose, and a number of oligosaccharides, was tested as a substrate for a number of biochemical activities of S. r n ~ t a n s . ~It’ could be fermented for growth and acid production but was poorly utilized for polysaccharide production and in vitro plaque formation. Moreover, while non-toxic in rats, it produced significantly less caries than sucrose and further work on its use as a sugar-substitute seems warranted. Studies on populations whose diets consist mainly of starchy foods and little or no sucrose, show a much lower caries prevalence compared with so-called developed nations.3z This has also been shown in experimental animals33 and may be due to the breakdown of starch by salivary alpha-amylase resulting in the formation of maltose which, as discussed below, does not promote plaque formation by potentially cariogenic streptococci. From the foregoing, it appears that, as well as starch, other substitutes such as xylitol would be equally or even more effective as cariostatic agents. Following adequate toxicity testing, they should be evaluated more extensively in humans but it should be borne in mind that total sucrose substitution would require a technological and cultural revolution.

Sugar additives While the total replacement of dietary sucrose appears to be impracticable, it may be feasible to minimise or even eliminate the cariogenicity of sucrose by adding certain compounds to foodstuffs. Among these are phosphates, low molecular weight dextrans and maltose. Phosphates. Many studies have shown that a variety of both inorganic and organic phosphates significantly reduce the level of caries in experimental animals fed highly cariogenic diets and this field has been recently reviewed.34 Generally, the more complex phosphates exert a greater cariostatic effect than simple phosphates and, of the former group, trimetaphosphate appears to Okada, S., and Kitahata, S.-Preparation and some properties ofsucrose-bound syrup. J. Japan. Food Ind., 22: 6-10, 1975. 3 1 Ikeda, T., Shiota, T., McGhee, J. R., Otake, S., Michalek, S. M., Ochial, K., Hirasawa, M., and Sugimoto, K.-Virulence of Streptococcus mutans: Comparison of the effects of a coupling sugar and sucrose on certain metabolic activities and cariogenicity. Infect. fmmun., 19: 2, 477-480 (Feb.) 1978. 32 Scherp, H. W.-Dental caries: Prospects for prevention. Science, 173: 4003, 1199-1205 (Sept.) 1971. Frostell, G . , and Baer, P. N.-Effect of sucrose, starch and a hydrogenated starch hydrolysate on dental caries in the rat. Acta Odontol. Scand., 29: 3, 253-259 (Sept.) 1971. 3 4 Lilienthal, B.-Phosphates and dental caries. Monographs in Oral Science, Vol. 6. Basel, S. Karger, 1977. 30

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be the most effective.35 Phosphates exert their effect(s) locally rather than systemically and among the properties that might be related to their anti-caries property are: reduction in solubility of hydroxyapatite; effects on the adsorption of salivary glycoproteins by enamel; interference with the formation of cariogenic plaque; and inhibition of bacterial fermentation of carbohydrates. In relation to the last-mentioned property, recent studies36. 3 7 have shown that phosphate has a negative effect on glycolysis in S. mutans, resulting in a decreased rate of lactic acid synthesis. Limited human studies in which inorganic or organic phosphate supplements have been added to various dietary components have not been particularly encouraging despite their success in experimental animals.34 The marked differences between humans and rodents with respect to salivary phosphate levels and plaque microbial flora may partly explain these discrepancies. Expectation of success with the organic phosphates was based on the widely held view that these compounds enter plaque and control enamel solution. However, more recent studies on phosphate levels in human plaque reveal that inorganic phosphate, glycero-phosphate and sucrose-phosphate may be incorporated into developing plaque but only glycero-phosphate has the ability to penetrate pre-formed plaque.3s, 39 Further studies on the conditions which may promote the entry of phosphates into plaque may facilitate further evaluation of these compounds in human clinical trials. Low molecular weight dextrans; maltose. Insoluble, high molecular weight glucans (dextrans), synthesized from sucrose by glucosyltransferases, are involved in the adherence of organisms such as S. mutans to the tooth surface.40 Soluble, low molecular weight (l0,OOCr 20,000) dextrans and maltose inhibit such synthesis in vitro, possibly by competing as glucosyl acceptor^.^'-^^ Moreover, when replacing some of the sucrose fed to hamsters harbouring streptococci capable of forming insoluble glucan, low molecular weight dextrans significantly reduced both plaque and caries.44 While it has

Harris, R. S.. Nizel, A. E., and Walsh, N. B.-The effect of phosphate stricture on dental caries development in rats. J. Dent. Res., 46: I , 290-294 (Jan.-Feb.) 1967. 3 6 White, G. E., Cooney, C. L., Sinskey, A. J.. and Miller, S. A,Continuous culture studies on the growth and physiology of Streptoroccusmutans. J. Dent. Res., 55: 2,239-243 (Mar.Apr.) 1976. 3 7 Brown, A. T., and Ruh, R.-Negative interaction of orthophosphate with glycolytic metabolism by Streplococcus mutams as a possible mechanism for dental caries reduction. Archs. Oral Biol., 22: 8, 521-524 (Sept.) 1977. 3 8 Tatevossian, A,, Edgar, W. M., and Jenkins, G. N.-Changes in the concentrations of phosphates in human plaque after the ingestion of sugar with and without added phosphates. Archs. Oral Biol., 20: 10, 617-625 (Oct.) 1975. J 9 Tatevossian, A., and Gould, C. T.-The composition of the aequeous phase in human dental plaque. Archs. Oral Biol., 21: 5, 319-323 (May) 1976. 40 Gibbons, R. J., and van Houte, J.-Bacterial adherence in oral microbial ecology. Ann. Rev. Microbiol., 29: 1 9 4 , 1975.

been argued that the levels of these additives are impracticably high,45 studies of this type should be extended.

Eliminating cariogenic bacteria The mechanical removal of plaque is not completely effective in eliminating caries, even when practised by highly motivated individuals. Since caries is a microbial disease, attempts have been made to control or prevent plaque formation by the use of antimicrobial agents, a subject that has recently been reviewed in some detaiL4” In assessing the use of any antimicrobial agent, the question of the “non-specific plaque hypothesis” versus the “specific plaque hypothesis” should be borne in mind.46 The former implies that both caries and periodontal disease result from the biochemical activities of the entire plaque flora and thus all plaques have equal pathogenic potential. The latter view is that only certain plaques cause infection because of the presence of pathogen(s) or a relative increase in the levels of particular indigenous plaque organisms or both of these. Bacteriological data46tend to support the specific plaque hypothesis. In parenthesis, it is worth noting that group studies have shown that elevated salivary levels of lactobacilli and S. mutans can be used for identifying children with a high caries risk4’. 4 8 but, unfortunately, such parameters have a very limited prognostic value in individual cases. The whole question of microbiological tests for caries susceptibility has been reviewed49 and, while it would be of extreme value, there is no reliable, rapid and inexpensive test that can be used by the dental practitioner. Antibacterial agents. Apart from its unpalatability and tendency to stain teeth, chlorhexidine, used as a daily

Kuramitsu, H. K.-Characterization of extracellular glucosyltransferase activity of Streptococcus mutans. Infect. Immun., 12: 4, 738-749 (Oct.) 1975. 4 2 Montville, T. J., Cooney, C. L., and Sinskey, A. J.-Measurement and synthesis of insoluble and soluble dextran by Streptococcus mutans. J. Dent. Res., 56: 8,983-989 (Aug.) 1977. Balekjian, A. Y., Longton. R. W.. Cole, J. S., and Guidry, M. S.-The effect of disaccharides on the plaque-forming potential ot Streptococcus mutans. J. Dent. Res., 56: 11, 1359-1363 (Nov.) 1977. 4 4 Gibbons, R. J., and Keyes, P. H.--Inhibition of insoluble dextran synthesis, plaque formation and dental caries in hamsters by low molecular weight dextrans. Archs. Oral Biol., 14: 6, 721-724 (June) 1969. 4 5 Gibbons, R. J., and van Houte, J.-Dental caries. Ann. Rev. Med., 26: 121-136, 1975. -46Loesche, W. J.-Chemotherapy of dental plaque infections. Oral Sciences Revs., 9: 65-107, 1976. 4 7 Krasse, B.-Approaches to prevention. In, Proc. Microbial aspects ot dental caries. Stiles, H. M. et a / . (Edits.), Sp. Suppl. Microbial. Abstrs., pp. 867-876, 1976. 4 8 Klock, B., and Krasse, B.-Effect of caries-preventive measures in children with high numbers of S.mufans and lactobacilli. Scand. 1. Dent. Res., 86: 4,221-230 (July) 1978. 4 9 Ellen, R. P.-Microbiological assays for dental caries and periodontal disease susceptibility. Oral Sciences Revs., 8: 3-15. 1976. ‘I

Australian Dental Journal, June, 1979 mouthwash, is one of the safest and most effective plaque control agents so far tested. Its efficacy lies mainly in its ability to adsorb to both soft and hard oral tissues from which it is slowly desorbed in an active form.46. Chemical analogues that are even more slowly released and do not stain teeth are actively being sought. Another group of chemicals with promising cariostatic potential are the 8-hydroxyquinolines. 5 1 Antibiotics. The use of antibiotics has been restricted on medical but vancomycin, which is nonabsorbable and has rather limited medical use, has been shown to reduce plaque49 but does not prevent its formation.s0 Kanamycin and spiramycin may also prove

Preventing the deleterious effects of cariogenic bacteria Unlike most other microbial diseases, caries has not yet been shown conclusively to be mono-aetiological in microbiological terms. In any case, the antimicrobial agents listed above are not specific and thus their continued use may indiscriminately remove from plaque many microbial species that actually play an anticariogenic role. For example, Veillonella alkalesrens has been shown to reduce caries in rats harbouring certain cariogenic strains of S . r n u t a n ~ . ~ ~ Interfering with microbial metabolism Rather than an attack on microbial viability, it might therefore be more rational to seek agents that would modify those biochemical activities thought to be important in the virulence of cariogenic bacteria. These would include modification or inhibition of the following:-sugar utilization and acid production; synthesis of extracellular polymers important for the structural integrity of plaque; synthesis of intracellular polysaccharides; glycoproteins thought to be involved in the primary microbial colonization of teeth. They would also include the degradation of pre-formed plaque and stimulation of the production of antibodies directed against cariogenic bacteria such as S . mutans. A good deal of research along these lines has been undertaken. For example, it would appear that the cariostatic effect of fluoride is due, in part, to its ability to interfere with both glucose transports3 and intracellular polysaccharide m e t a b o l i ~ r n There . ~ ~ are at least

s2

s3

D

Loe. H.-Does chlorhexidine have a place in the prophylaxis of dental diseases? J. Periodont. Res., 8 : suppl. 12, 93-99, 1973. Mirth. D. B.. Chite. A. F., and Schuster, G . S.-8-hydroxyquinolines with the potential for long-term anticaries activity: Design, synthesis, and in v i m evaluation. J. Dent. Res.. 57: I. 65-71 (Jan.) 1978. Hoeven. J . S . van der, Toorop, A. I., and Mikx, F. H . M.Symbiotic relationship of Veillonellu alkalrscens and Strrptococrus mufans in dental plaque in gnotobiotic rats. Caries Res.. 12: 142Zl47. 1978. Hamilton, I. R.-Effects of fluoride on enzymatic regulation of bacterial carbohydrate metabolism. Caries Res. I 1 : suppl. I, 262-291, 1977.

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two distinct classes of glucans, the glucose polymers considered to be important in the structural integrity of plaque formed by S . mutans and synthesized from sucrose by glucosyltransferases. One is predominantly alpha 1-16 linked and the other, a more insoluble glucan (“mutan”), has a high proportion of alpha 1-13 and 1+4 bonds.55The latter appears to be an important virulence factor in the cariogenicity of S . mutans.56The enzymes catalyzing the synthesis of mutans have not yet been purified and at present there is no way of inhibiting their activity in plaque, although attempts have recently been made.57 Attempts to degrade preformed plaque have not been uniformly effective. While alpha 1-16 glucan hydrolysases (dextranases) have not been successful, mixtures of these and alpha I -13 glucan hydrolysases (mutanases) appear to offer greater promise.2 Inhibition of microbial colonization As mentioned above. glucan synthesis is of paramount importance in plaque formation by S . mutans, in the sense that it promotes cell-to-cell adhesion and therefore their accumulation. However, recent work indicates that glucans are not necessary for the primary attachment of this organism to teeth and that this process is brought about by the interaction of cell-surface moieties and components of the saliva-derived enamel p e l l i ~ l e . ~ ~ Such interaction might be mediated by calcium ion bridging. s9 Cationic substances, which will compete with calcium ions, should inhibit this bacterial adsorption to teeth; such a compound is chlorhexidine which, as mentioned above, is indeed an effective anti-plaque agent. The binding might also be effected by lectins. a class of proteins known to be of importance in binding cells together.60 Certain salivary glycoproteins can act as lectins; some of them may enhance plaque accumulation but, more importantly, others may agglutinate Hamilton, 1. R., and Ellwood. D. C.- Effects of fluoride on carbohydrate metabolism by washed cells of Streptococcus mufans grown at various pH values in a chemostat. Infect. Immun., 19: 2, 434442 (Feb.) 1978. s 5 Ceska, M., Granath, K., Normann, B., and Guggenheim. B.-Structural and enzymatic studies on glucans synthesized with glucosyltransferases of some strains of oral streptococci. Actd Chem. Scdnd., 26: 2223-2230. 1972. Freedman, M., Birked, D., and Granath, K.--Analyses of glucans from cariogenic and mutant Streptococcus mutans. Infect. Immuu., 21: 1, 17-27 (July) 1978. s’ Ciardi, J . E., Bowen, W. H., and Rolla, G.-The effect of antibacterial compounds on glucosyltransferase activity from Streptococcus niufans. Archs. Oral Biol., 23: 4, 301305 (Apr.) 1978. 5 8 Clark, W. B., and Gibbons, R. J.-Influence of salivary components and extracellular polysaccharide synthesis from sucrose on the attachment of Streptococcus mutans 6715 to hydroxyapatite surfaces. Infect. Immun., 18: 2, 51L523 (Nov.) 1977. s g Rolla, G.- Inhibition of adsorption-general considerations. I n . Proc. microbial asDects of dental caries. Stiles. H . M . . et a1 (Edits ), Sp Suppl Microbiology Abstracts, 11’ 309-324, 1976 O n Sharon, N . -Lectins. Scient. Amer., 236: 6, 108-1 19 (June) 1977. s4

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bacteria in saliva thereby preventing microbial colonization on the tooth surface.61 This latter phenomenon has suggested the development of a new class of antibiotics aimed at combating microbial infection by blocking the adhesion of pathogens to susceptible cells in various ways.62 Such an approach is of significance in the prevention of caries. Immunization; a caries vaccine Several workers have obtained evidence suggesting that immunization of rodents, or monkeys with killed S. mutans, reduces caries induced by this organism :63 other studies have produced results showing no protection at all.64 In humans, attempts have been made to associate levels of caries experience with serum or salivary levels

''

Levine, M. J.. Herzberg, M. C., Levine, M. S., Ellison, S. A,. Stinson, M. W., Li, H. C., and van Dyke, T.-Specificity of salivary-bacterial interactions: Role of terminal sialic acid residues in the interaction of salivary glycoproteins with Sfreptococcus sanguis and Streprococcus mutans. Infect. Immun., 19: I . 107-115 (Jan.) 1978. '* Costerton, J. W., Geesey, G. G., and Cheng, K.-J.-How bacteria stick. Scient. Amer., 238: I. 86-95 (Jan.) 1978. Taubman, M. A., and Smith, D. J.-EtTect of local immunization with Sfreptococcus mufans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats. Infect. lmmun., 9: 6, 1079-1091 (June) 1974. 6 4 Tanzer, J. M., Hageage, G. J., and Larson, R. H.-Inability to immunologically protect rats against smooth surface caries. Abst. No. 466, 48th meeting, I.A.D.R. (U.S.), 1970. '' Kennedy, A. E., Shklair, 1. L., Hayashi, J. A,, and Bahn. A. N.--Antibodies to cariogenic streptococci in humans. Archs. Oral Biol., 13: 10, 1275-1278 ( a t . ) 1968. 6 n Lehner. T., Wilton, J. M. A,, and Ward. R. G.-Serum antibodies in dental caries in man. Archs. Oral Biol., 15: 6, 481-490 (June) 1970. O' Sims, W. -The concept of immunity in dental caries 1. General considerations. Oral Surg., Oral Med., Oral Path., 30: 5 , 67(F677 (Nov.) 1970. O " Kuramitsu, H. K..and lngersoll, L.-Differential inhibition of Streptococcus mutans in vitro adherence by anti-glucosyltransferase antibodies. Infect. lmmun., 13: 6. 1775 I777 (June) 1976. 6u Genco, R. J.-Summation of final general discussion. In. Immunologic aspects of dental caries. Bowen, W. H. et a / . (Edits.), Sp. Suppl. Microbiol. Abstrs., pp. 221-222, 1976. '' van der Rijn, I., and Zabriskie, J. B.-Immunological relationship between Sfreptococcus mutans and human myocardium. In, Immunologic aspects of dental caries. Bowen, W. H.et a / . , (Edits.), Sp. Suppl. Microbiol. Abstrs., pp. 187- 194. 1976. " Bowen, W. H.-Assessments and recommendations for future research: Summary of discussion. In, Immunologic aspects of dental caries. Bowen, W. H. et a/. (Edits.), Sp. Suppl. Microbiol. Abstrs., p. 219, 1976. 'z Taubman. M. A,, and Smith, D. J.-Effects oflocal immunization with glucosyltransferase fractions from Sfrepfococcus mufans on dental caries in rats and hamsters. J. Immunol., 118: 2, 710-720 (Feb.) 1977. " Krasse, B., and Jordan, H. V.-Effect of orally applied vaccines on oral colonization by Strepfococcus mufans in rodents. Archs. Oral Biol., 22: 8-9, 479484 (Aug.-Sept.) 1977. '' Michalek, S. M., McGhee, J. R., and Babb, J. L.-Effective immunity to dental caries: Dose-dependent studies of secretory immunity by oral administration of Sfreptococcus mutans to rats. Infect. Immun., 19: I , 217-224 (Jan.) 1978.

Australian Dental Journal, June, 1979 or both of immunoglobulin A(1gA) antibody specific for S. mutans but again the results are ~ o n f l i c t i n g .6~6~ . One of the possible reasons for this revolves around the point that caries-free subjects are not necessarily cariesimmune or caries-resistant : they may never have been exposed to the appropriate dietetic and bacterial

condition^.^^ Studies in vitro have shown that IgG or IgA antibodies or both against S . mutnns glucosyltransferases (GT) inhibit glucan synthesis and prevent plaque formation by sucrose-grown cultures of S. Arising from this paper, the point should be made that only the GT synthesizing insoluble glucan may prove the most effective immunogen. This is of particular relevance to earlier work using GT of doubtful purity, since some GT induce antibodies that actually stimulate G T activity leading to the synthesis of insoluble glucan and therefore actually promoting caries.69 Despite an increasing volume of literature on the subject of dental caries vaccines, a number of problems remain. For example, most animal work has involved the use of whole cells of S. mufans as the immunogen. However, these strains contain an antigen crossreacting with heart tissue and this means that a single infection with a Group A Streptococcus pyogenes strain, coupled with a stimulus from S. mutans whole cells, could trigger off immunopathological reactions of the rheumatic fever type.70 The need to identify and purify the protective immunogen(s) in S. muruns thus becomes of extreme importance. Among the most likely candidates would appear to be purified GT, cell wall polysaccharides and lipoteichoic acid. Other problems relate to the timing and route of administration of the selected immunogen(s). With respect to timing, it is generally considered that the optimum time for immunization would be following the eruption of the first permanent molar.71 Regarding the route of administration, local immunization in the vicinity of the salivary glands,72 topical application to oral tissues,73 and ingestion74 have been suggested. In summary, a number of problems remain unsolved. and the use of an anti-caries vaccine for humans cannot be contemplated at present. General summary and conclusions A number of measures by wtiich potintially cariogenic bacteria can be eliminated or their deleterious activities minimized, are discussed. Many of them, such as chlorhexidine mouth rinses or the reduction of the cariogenic challenge in the diet may prove valuable at the individual level. At the public health level, where motivation is unnecessary and irrelevant, water fluoridation is the only currently practical proposal. Department of Oral Biology, The University of Adelaide, Adelaide, S.A., 5001.

Biological methods of dental caries prevention. A review.

Australian Dental Journal, June, 1979 153 Volume 24, No. 3 Biological methods of dental caries prevention. A review A. H. Rogers, M.Sc.(Adel.), Ph...
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