title: Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus mutans through Multiple Mechanisms.
abstract: Biochemical and genetic aspects of the metabolism of the amino sugars N-acetylglucosamine (GlcNAc) and glucosamine (GlcN) by commensal oral streptococci and the effects of these sugars on interspecies competition with the dental caries pathogen Streptococcus mutans were explored. Multiple S. mutans wild-type isolates displayed long lag phases when transferred from glucose-containing medium to medium with GlcNAc as the primary carbohydrate source, but commensal streptococci did not. Competition in liquid coculture or dual-species biofilms between S. mutans and Streptococcus gordonii showed that S. gordonii was particularly dominant when the primary carbohydrate was GlcN or GlcNAc. Transcriptional and enzymatic assays showed that the catabolic pathway for GlcNAc was less highly induced in S. mutans than in S. gordonii Exposure to H2O2, which is produced by S. gordonii and antagonizes the growth of S. mutans, led to reduced mRNA levels of nagA and nagB in S. mutans When the gene for the transcriptional regulatory NagR was deleted in S. gordonii, the strain produced constitutively high levels of nagA (GlcNAc-6-P deacetylase), nagB (GlcN-6-P deaminase), and glmS (GlcN-6-P synthase) mRNA. Similar to NagR of S. mutans (NagRSm), the S. gordonii NagR protein (NagRSg) could bind to consensus binding sites (dre) in the nagA, nagB, and glmS promoter regions of S. gordonii Notably, NagRSg binding was inhibited by GlcN-6-P, but G-6-P had no effect, unlike for NagRSm This study expands the understanding of amino sugar metabolism and NagR-dependent gene regulation in streptococci and highlights the potential for therapeutic applications of amino sugars to prevent dental caries.
  
  
  
  Amino sugars are abundant in the biosphere, so the relative efficiency of particular bacteria in a given microbiota to metabolize these sources of carbon and nitrogen might have a profound impact on the ecology of the community. Our investigation reveals that several oral commensal bacteria have a much greater capacity to utilize amino sugars than the dental pathogen Streptococcus mutans and that the ability of the model commensal Streptococcus gordonii to compete against S. mutans is substantively enhanced by the presence of amino sugars commonly found in the oral cavity. The mechanisms underlying the greater capacity and competitive enhancements of the commensal are shown to depend on how the genes for the catabolic enzymes are regulated, the role of the allosteric modulators affecting such regulation, and the ability of amino sugars to enhance certain activities of the commensal that are antagonistic to S. mutans.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USAStanford University lzeng@dental.ufl.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USAStanford University.
authors.forename: Tanaz
authors.initials: T
authors.lastname: Farivar
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USAStanford University.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burne
mesh_terms: D000606:Amino Sugars / Q000378:metabolism*; D000898:Antibiosis; D020869:Gene Expression Profiling; D053858:Metabolic Networks and Pathways; D054773:Streptococcus gordonii / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D013295:Streptococcus mutans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D000606:Amino Sugars