Inhibition of caries in hamsters by 2-deoxy-D-glucose.
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Biomedical subjects
Publications and source records attributed to R J Fitzgerald.
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Consideration of nutritional factors as determinants of oral microbial ecology leads to the conclusion that endogenous factors play a dominant role. It is the interactions between specific microorganisms and nutritional and other factors provided by the host that selectively determine the kinds of microorganisms which willinitially reside in the oral cavity and the sites which they will colonize. The persistence of these original "colonists" in their respective ecologic niches will depend in part on the accessibility of endogenous nutrients variously provided by saliva, tissue exudates, crevicular fluids, or degenerating host cells. It will also depend on their response to and interaction with microorganisms which immigrate to that site subsequently. The microbial ecology of a given site is therefore rarely uncomplicated, the notable exception occurring at the most microscopic level where one may encounter microcolonies of individual species within more heterogenous populations of microorganisms. The extent of this heterogeneity quantitatively and qualitatively is a reflection of the degree to which the interactions between the resident flora and the new arrivals, plus the local environmental changes which they both generate, serve to promote or to discourage the survival and growth of the individual species. This element of heterogeneity in a dynamic system with its inherent potential for variation makes it possible for relatively minor changes in local environmental conditions to result in significant differences in the microflora between one site and another even though they may be in close proximity to each other. Once this concept is appreciated it becomes easy to understand how disease processes such as dental caries may affect specific areas of a tooth while nearby areas are unaffected. The effects of exogenous nutrients on the ecology of the oral microbiota, nevertheless cannot be ignored. The diet may modulate such endogenous factors as the salivary secretions and the local resistance of the gingival tissues to infections. Although at our present state of knowledge the direct influence of dietary proteins and fats on the oral microbiota is thought to be of relatively minor consequence, dietary carbohydrates are of major ecological significance. Dietary sugars provide readily available substrates for the oral microorganisms, most of which depend on carbohydrates for energy sources. The metabolism of dietary sucrose by S. sanguis and S. mutans with the productions of acids and intracellular and extracellular polysaccharides has specific influence on the microbial composition, metabolic activities, and mass of coronal plaque. The ready availability of dietary carbohydrates undoubtedly influences the microflora of other parts of the oral cavity as well, eic species or indirectly through the interactions of other organisms with them...
The growth response of Streptococcus sanguis groups 1:A and 1:B in a complete chemically defined medium was not influenced by the oxygen concentration of the growth atmosphere. All of the cultures required cysteine and arginine; tyrosine and branched-chain amino acids were frequently required. Proteolysis of casein, mucin, and the anionic proteins of germfree rat saliva by S. sanguis was demonstrated. Hydrolytic activity toward casein was found in the soluble contents of the cells and in the cellular debris after disruption of the cells, with the soluble fractions exhibiting greater proteolytic activity toward casein. The soluble fractions from S. sanguis did not hydrolyze mucin, but this substrate was hydrolyzed by the cell debris fraction. When the amino acid requirements and proteolytic activity of S. sanguis and S. mutans were compared, these two oral streptococcal species exhibited distinct and characteristic differences.
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The growth response of Streptococcus mutans representing antigenic type a or d in a chemically defined medium was influenced by the oxygen concentration of the growth atmosphere. Under controlled aerobic (1.5% O(2)) conditions these cultures attained a greater density than when the atmosphere contained 0.006% O(2) or less. The growth of S. mutans strains representing antigenic types b or c in the defined medium was independent of the oxygen concentration of the growth environment. Under the conditions used in this study, none of the strains tested could utilize ammonium ion as a sole source of nitrogen for growth. The requirement for certain amino acids and inhibition by other amino acids varied with antigenic type and relative oxygen concentration of the growth environment. Under conditions where the atmospheric oxygen was reduced to 0.0006% O(2) or less, the amino acid requirements of the cultures became either more numerous or more stringent. S. mutans strains of type c generally required the least number of amino acids, whereas cultures of type d had more numerous requirements. Nearly every culture tested under the anaerobic atmosphere was inhibited by one of the branched-chain amino acids, leucine, valine, or isoleucine. Methionine and lysine were also found to be inhibitory, particularly toward the type c strains.
The virulence of cell surface-associated, glucan synthesis-defective mutants of Streptococcus mutans strain 6715-13 was studied. Representatives from three groups of such mutants were tested for their pathogenicity in conventionalized, specific pathogen-free rats and gnotobiotic rats. The mutants differ from the wild-type strain in that each failed to form plaque on the smooth surfaces of the teeth and to cause smooth surface caries. Although the ability to form cell surface-associated glucans was not a strict requirement for the expression of virulence in the sulci of the teeth, it augmented virulence at such sites. However, the ability to form cell surface-associated glucans and to adhere to the teeth was clearly not the sole determinant of virulence.
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A variety of antibiotic and chemotherapeutic agents were tested for their ability to inhibit the development of dental caries in Sprague-Dawley rats receiving the drugs in a coarse-particle sucrose-containing diet. Drugs which inhibit gram-positive microorganisms were effective inhibitors of caries, whereas agents which are active solely against gram-negative bacteria did not inhibit caries development. In vivo efficacy of the agents tested generally, but not invariably, paralleled in vitro inhibition of the growth of Streptococcus mutans strain FA-1, an organism which was isolated from carious Sprague-Dawley rats and which is known to induce caries in gnotobiotic Sprague-Dawley rats. Caries was significantly inhibited when 1-ephenamine penicillin (20 units/mg) was administered intermittently in the diet, 1 day per week or 1 week of every 4 weeks, but protection against caries was greatest when the same amount of the drug was fed continuously.
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Glucose-grown washed cells of streptococci similar to Streptococcus mutans, which contain cell-bound dextransucrase, have been observed to agglutinate upon the addition of high molecular weight dextran. Low molecular weight dextran or unrelated polysaccharides were ineffective. Agglutination also occurred upon addition of sucrose, which can be converted into dextran, but not with other mono- and disaccharides. Other bacteria, including species capable of synthesizing dextrans, were not observed to exhibit this phenomenon. Cells of S. mutans agglutinated upon addition of dextran over a wide pH range, but maximal sensitivity to dextran occurred at pH 8.5. At this pH, such cells can be used for a simple, specific, and exquisitely sensitive qualitative assay for high molecular weight dextran, for addition of 6 ng of dextran with a molecular weight of 2 x 10(6) (i.e., approximately three molecules per cell) caused detectable agglutination. High concentrations of glucose, levan, and dextran of molecular weight of 2 x 10(4) inhibited the reaction. Fluorescein-labeled cells of S. mutans were observed to adhere to dextran-containing plaques and dextran-treated teeth, suggesting that this phenomenon may be of importance in the formation of streptococcal dental plaques. The mechanism responsible for dextraninduced agglutination appears to involve the affinity of a receptor site, possibly dextransucrase, on the surface of several cells for common dextran molecules.
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