1887

Abstract

Aciduricity is a major cariogenic characteristic of , and various genes have been implicated in this ability of . Sixteen 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 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 Dgk homologue. R59949, but not R59022, significantly reduced the growth of 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 .

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2011-05-01
2024-03-29
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References

  1. Ahn S. J., Wen Z. T., Burne R. A. 2006; Multilevel control of competence development and stress tolerance in Streptococcus mutans UA159. Infect Immun 74:1631–1642 [View Article][PubMed]
    [Google Scholar]
  2. Biswas S., Biswas I. 2005; Role of HtrA in surface protein expression and biofilm formation by Streptococcus mutans . Infect Immun 73:6923–6934 [View Article][PubMed]
    [Google Scholar]
  3. Boyd D. A., Cvitkovitch D. G., Bleiweis A. S., Kiriukhin M. Y., Debabov D. V., Neuhaus F. C., Hamilton I. R. 2000; Defects in d-alanyl-lipoteichoic acid synthesis in Streptococcus mutans results in acid sensitivity. J Bacteriol 182:6055–6065 [View Article][PubMed]
    [Google Scholar]
  4. Cvitkovitch D. G., Gutierrez J. A., Behari J., Youngman P. J., Wetz J. E. Jr, Crowley P. J., Hillman J. D., Brady L. J., Bleiweis A. S. 2000; Tn917-lac mutagenesis of Streptococcus mutans to identify environmentally regulated genes. FEMS Microbiol Lett 182:149–154 [View Article][PubMed]
    [Google Scholar]
  5. De Chaffoy de Courcelles D., Roevens P., Van Belle H. 1985; R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J Biol Chem 260:15762–15770[PubMed]
    [Google Scholar]
  6. Dong Y., Palmer S. R., Hasona A., Nagamori S., Kaback H. R., Dalbey R. E., Brady L. J. 2008; Functional overlap but lack of complete cross-complementation of Streptococcus mutans and Escherichia coli YidC orthologs. J Bacteriol 190:2458–2469 [View Article][PubMed]
    [Google Scholar]
  7. Griswold A. R., Chen Y. Y., Burne R. A. 2004; Analysis of an agmatine deiminase gene cluster in Streptococcus mutans UA159. J Bacteriol 186:1902–1904 [View Article][PubMed]
    [Google Scholar]
  8. Hanahan D. 1983; Studies on transformation of Escherichia coli with plasmids. J Mol Biol 166:557–580 [View Article][PubMed]
    [Google Scholar]
  9. Hanna M. N., Ferguson R. J., Li Y. H., Cvitkovitch D. G. 2001; uvrA is an acid-inducible gene involved in the adaptive response to low pH in Streptococcus mutans . J Bacteriol 183:5964–5973 [View Article][PubMed]
    [Google Scholar]
  10. Hasin M., Kennedy E. P. 1982; Role of phosphatidylethanolamine in the biosynthesis of pyrophosphoethanolamine residues in the lipopolysaccharide of Escherichia coli . J Biol Chem 257:12475–12477[PubMed]
    [Google Scholar]
  11. Hasona A., Crowley P. J., Levesque C. M., Mair R. W., Cvitkovitch D. G., Bleiweis A. S., Brady L. J. 2005; Streptococcal viability and diminished stress tolerance in mutants lacking the signal recognition particle pathway or YidC2. Proc Natl Acad Sci U S A 102:17466–17471 [View Article][PubMed]
    [Google Scholar]
  12. Jiang Y., Sakane F., Kanoh H., Walsh J. P. 2000; Selectivity of the diacylglycerol kinase inhibitor 3-[2-(4-[bis-(4-fluorophenyl)methylene]-1-piperidinyl)ethyl]-2, 3-dihydro-2-thioxo-4(1H)quinazolinone (R59949) among diacylglycerol kinase subtypes. Biochem Pharmacol 59:763–772 [View Article][PubMed]
    [Google Scholar]
  13. Kanoh H., Yamada K., Sakane F. 2002; Diacylglycerol kinases: emerging downstream regulators in cell signaling systems. J Biochem 131:629–633[PubMed] [CrossRef]
    [Google Scholar]
  14. Kawada-Matsuo M., Shibata Y., Yamashita Y. 2009; Role of two component signaling response regulators in acid tolerance of Streptococcus mutans . Oral Microbiol Immunol 24:173–176 [View Article][PubMed]
    [Google Scholar]
  15. Korithoski B., Lévesque C. M., Cvitkovitch D. G. 2007; Involvement of the detoxifying enzyme lactoylglutathione lyase in Streptococcus mutans aciduricity. J Bacteriol 189:7586–7592 [View Article][PubMed]
    [Google Scholar]
  16. Kremer B. H., Van der Kraan M., Crowley P. J., Hamilton I. R., Brady L. J., Bleiweis A. S. 2001; Characterization of the sat operon in Streptococcus mutans: evidence for a role of Ffh in acid tolerance. J Bacteriol 183:2543–2552 [View Article][PubMed]
    [Google Scholar]
  17. Lemos J. A., Burne R. A. 2002; Regulation and physiological significance of ClpC and ClpP in Streptococcus mutans . J Bacteriol 184:6357–6366 [View Article][PubMed]
    [Google Scholar]
  18. Lis M., Kuramitsu H. K. 2003; The stress-responsive dgk gene from Streptococcus mutans encodes a putative undecaprenol kinase activity. Infect Immun 71:1938–1943 [View Article][PubMed]
    [Google Scholar]
  19. Loesche W. J. 1986; Role of Streptococcus mutans in human dental decay. Microbiol Rev 50:353–380[PubMed]
    [Google Scholar]
  20. Mérida I., Avila-Flores A., Merino E. 2008; Diacylglycerol kinases: at the hub of cell signalling. Biochem J 409:1–18 [View Article][PubMed]
    [Google Scholar]
  21. Perry D., Wondrack L. M., Kuramitsu H. K. 1983; Genetic transformation of putative cariogenic properties in Streptococcus mutans . Infect Immun 41:722–727[PubMed]
    [Google Scholar]
  22. Preiss J., Loomis C. R., Bishop W. R., Stein R., Niedel J. E., Bell R. M. 1986; Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells. J Biol Chem 261:8597–8600[PubMed]
    [Google Scholar]
  23. Quivey R. G., Kuhnert W. L., Hahn K. 2001; Genetics of acid adaptation in oral streptococci. Crit Rev Oral Biol Med 12:301–314 [View Article][PubMed]
    [Google Scholar]
  24. Raetz C. R., Newman K. F. 1979; Diglyceride kinase mutants of Escherichia coli: inner membrane association of 1,2-diglyceride and its relation to synthesis of membrane-derived oligosaccharides. J Bacteriol 137:860–868[PubMed]
    [Google Scholar]
  25. Rotering H., Raetz C. R. 1983; Appearance of monoglyceride and triglyceride in the cell envelope of Escherichia coli mutants defective in diglyceride kinase. J Biol Chem 258:8068–8073[PubMed]
    [Google Scholar]
  26. Sambrook J., Russell D. W. 2001 Molecular Cloning: a Laboratory Manual, 3rd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  27. Sawatari Y., Yokota A. 2007; Diversity and mechanisms of alkali tolerance in lactobacilli. Appl Environ Microbiol 73:3909–3915 [View Article][PubMed]
    [Google Scholar]
  28. Shibata Y., Yamashita Y., Ozaki K., Nakano Y., Koga T. 2002; Expression and characterization of streptococcal rgp genes required for rhamnan synthesis in Escherichia coli . Infect Immun 70:2891–2898 [View Article][PubMed]
    [Google Scholar]
  29. Shibata Y., Van der Ploeg J. R., Kozuki T., Shirai Y., Saito N., Kawada-Matsuo M., Takeshita T., Yamashita Y. 2009; Kinase activity of the dgk gene product is involved in the virulence of Streptococcus mutans . Microbiology 155:557–565 [View Article][PubMed]
    [Google Scholar]
  30. Tanzer J. M., Livingston J., Thompson A. M. 2001; The microbiology of primary dental caries in humans. J Dent Educ 65:1028–1037[PubMed]
    [Google Scholar]
  31. Topham M. K., Prescott S. M. 1999; Mammalian diacylglycerol kinases, a family of lipid kinases with signaling functions. J Biol Chem 274:11447–11450 [View Article][PubMed]
    [Google Scholar]
  32. Van Blitterswijk W. J., Houssa B. 2000; Properties and functions of diacylglycerol kinases. Cell Signal 12:595–605 [View Article][PubMed]
    [Google Scholar]
  33. Walsh J. P., Loomis C. R., Bell R. M. 1986; Regulation of diacylglycerol kinase biosynthesis in Escherichia coli. A trans-acting dgkR mutation increases transcription of the structural gene. J Biol Chem 261:11021–11027[PubMed]
    [Google Scholar]
  34. Wen Z. T., Burne R. A. 2004; LuxS-mediated signaling in Streptococcus mutans is involved in regulation of acid and oxidative stress tolerance and biofilm formation. J Bacteriol 186:2682–2691 [View Article][PubMed]
    [Google Scholar]
  35. Wen Z. T., Suntharaligham P., Cvitkovitch D. G., Burne R. A. 2005; Trigger factor in Streptococcus mutans is involved in stress tolerance, competence development, and biofilm formation. Infect Immun 73:219–225 [View Article][PubMed]
    [Google Scholar]
  36. Wen Z. T., Baker H. V., Burne R. A. 2006; Influence of BrpA on critical virulence attributes of Streptococcus mutans . J Bacteriol 188:2983–2992 [View Article][PubMed]
    [Google Scholar]
  37. Yamashita Y., Takehara T., Kuramitsu H. K. 1993; Molecular characterization of a Streptococcus mutans mutant altered in environmental stress responses. J Bacteriol 175:6220–6228[PubMed]
    [Google Scholar]
  38. Yamashita Y., Tsukioka Y., Nakano Y., Tomihisa K., Oho T., Koga T. 1998; Biological functions of UDP-glucose synthesis in Streptococcus mutans . Microbiology 144:1235–1245 [View Article][PubMed]
    [Google Scholar]
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