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Biochemical and genetic aspects of the metabolism of the amino sugarsN -acetylglucosamine (GlcNAc) and glucosamine (GlcN) by commensal oral streptococci and the effects of these sugars on interspecies competition with the dental caries pathogenStreptococcus mutans were explored. MultipleS. 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 betweenS. mutans andStreptococcus gordonii showed thatS. 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 inS. mutans than inS. gordonii . Exposure to H2 O2 , which is produced byS. gordonii and antagonizes the growth ofS. mutans , led to reduced mRNA levels ofnagA andnagB inS. mutans . When the gene for the transcriptional regulatory NagR was deleted inS. gordonii , the strain produced constitutively high levels ofnagA (GlcNAc-6-P deacetylase),nagB (GlcN-6-P deaminase), andglmS (GlcN-6-P synthase) mRNA. Similar to NagR ofS. mutans (NagRSm ), theS. gordonii NagR protein (NagRSg ) could bind to consensus binding sites (dre ) in thenagA ,nagB , andglmS promoter regions ofS. 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.IMPORTANCE 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 pathogenStreptococcus mutans and that the ability of the model commensalStreptococcus gordonii to compete againstS. 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 toS. mutans .

Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus mutans through Multiple Mechanisms