Sugar Metabolism In Lactic Acid and Oral Bacteria

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Dietary sucrose is a major contributor to pathogenicity of oral bacteria. For example, in the etiology of dental caries : (1) sucrose provides the building blocks for synthesis of glycans that facilitate adherence of Streptococcal species to the tooth surface, and (2) bacterial fermentation of the sugar generates lactic acid that causes demineralization of tooth enamel. Sucrose itself comprises glucose and fructose molecules that are linked between carbon atom 1 of the former and carbon atom 2 of the latter. Sucrose is phosphorylated simultaneously with transport into the bacteria, where it is subsequently hydrolyzed by an enzyme designated sucrose 6-phosphate hydrolase (S6PH). Modification of the glucosyl- linkages between C1 of glucose and the remaining five carbon atoms of fructose yield five analogs of sucrose designated : trehalulose (1-1), turanose (1-3), maltulose (1-4), leucrose (1-5) and palatinose (1-6).In contrast to sucrose, the isomeric compounds do not support growth of oral microorganisms, including streptococcal species. Two of these relatively sweet analogs, palatinose and leucrose, are produced on an industrial scale and - by virtue of their non-cariogenicity - are potential substitutes for dietary sucrose. Why organisms such as Streptococcus mutans fail to metabolize the sucrose isomers has never been established, and is a topic that we have recently addressed. Major accomplishments included:(i) the discovery of growth of Klebsiella pneumoniae on sucrose isomers, (ii) the first biosynthesis of all five phosphorylated isomers of sucrose, and (iii) the demonstration that sucrose-6-phosphate hydrolase is unable to catalyze the hydrolysis of any of these phosphorylated derivatives. Remarkably, the isomeric phosphates are hydrolyzed by an NAD and metal dependent phospho-alpha glucosidase.Molecular dynamics analysis suggests that solution-state conformational differences between the compact globular sucrose molecule, and the linearly extended forms of the isomers, are the basis for substrate discrimination by the two enzymes. Our findings provide insight to the rational design and synthesis of sucrose analogs that (by inactivation of sucrose-6-phosphate hydrolase) may permit selective targeting and inhibition of growth of caries-inducing bacteria such as Streptococcus mutans and Streptococcus sobrinus.