title: Streptococcus mutans diacylglycerol kinase homologue: a potential target for anti-caries chemotherapy.
abstract: Aciduricity is a major cariogenic characteristic of Streptococcus mutans, and various genes have been implicated in this ability of S. mutans. Sixteen S. mutans mutant strains, each defective in a different gene, were constructed and their aciduricity was assessed. Of the mutants, the diacylglycerol kinase (Dgk) homologue mutant and the glucose-1-phosphate uridylyltransferase mutant strains displayed distinctly attenuated aciduricity when grown at pH 5.5. Considering the delayed growth rate of the latter at neutral pH, the dgk homologue appeared to be a gene responding specifically to pH reduction among the 16 genes tested. Two known eukaryotic Dgk inhibitors, R59949 and R59022, were selected as candidate inhibitors of the S. mutans Dgk homologue. R59949, but not R59022, significantly reduced the growth of S. mutans at pH <5.4. R59949 did not affect either the final pH of the medium or the internal pH of the organism. Furthermore, R59949 inhibited about 20 % of Dgk kinase activity. Novel derivatives of R59949 may be useful for preventing the development of dental caries caused by S. mutans.
authors.affiliation: Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kawada-Matsuo
authors.affiliation: Biosignal Research Center, Kobe University, Kobe, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shirai
authors.affiliation: Biosignal Research Center, Kobe University, Kobe, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Saito
authors.affiliation: Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Section of Preventive and Public Health Dentistry, Division of Oral Health, Growth and Development, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D002327:Cariostatic Agents / Q000494:pharmacology; D003731:Dental Caries / Q000188:drug therapy* / Q000382:microbiology*; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005798:Genes, Bacterial; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D010880:Piperidines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology; D013295:Streptococcus mutans / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D002327:Cariostatic Agents; D004791:Enzyme Inhibitors; D010880:Piperidines; D011744:Pyrimidinones; D052999:Quinazolinones; D013844:Thiazoles; C058544:R 59949; C047505:R 59022; D019852:Diacylglycerol Kinase