1887

Abstract

in dental biofilms is regularly exposed to cycles of acidic pH during the ingestion of fermentable dietary carbohydrates. The ability of to tolerate low pH is crucial for its virulence and pathogenesis in dental caries. To better understand its acid tolerance mechanisms, we performed genome-wide transcriptional analysis of in response to an acidic pH signal. The preliminary results showed that adaptation of to pH 5.5 induced differential expression of nearly 14 % of the genes in the genome, including 169 upregulated genes and 108 downregulated genes, largely categorized into nine functional groups. One of the most interesting findings was that the genes encoding multiple two-component systems (TCSs), including CiaHR, LevSR, LiaSR, ScnKR, Hk/Rr1037/1038 and ComDE, were upregulated during acid adaptation. Real-time qRT-PCR confirmed the same trend in the expression profiles of these genes at pH 5.5. To determine the roles of these transduction systems in acid adaptation, mutants with a deletion of the histidine-kinase-encoding genes were constructed and assayed for the acid tolerance response (ATR). The results revealed that inactivation of each of these systems resulted in a mutant that was impaired in ATR, since pre-exposure of these mutants to pH 5.5 did not induce the same level of protection against lethal pH levels as the parent did. A competitive fitness assay showed that all the mutants were unable to compete with the parent strain for persistence in dual-strain mixed cultures at acidic pH, although, with the exception of the mutant in , little effect was observed at neutral pH. The evidence from this study suggests that the multiple TCSs are required for to orchestrate its signal transduction networks for optimal adaptation to acidic pH.

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2009-10-01
2019-10-17
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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.[CrossRef]
    [Google Scholar]
  2. Ajdic, D. & Pham, V. T. ( 2007; ). Global transcriptional analysis of Streptococcus mutans sugar transporters using microarrays. J Bacteriol 189, 5049–5059.[CrossRef]
    [Google Scholar]
  3. Ajdic, D., McShan, W. M., McLaughlin, R. E., Savic, G., Chang, J., Carson, M. B., Primeaux, C., Tian, R., Kenton, S. & other authors ( 2002; ). Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc Natl Acad Sci U S A 99, 14434–14439.[CrossRef]
    [Google Scholar]
  4. Bender, G. R., Sutton, S. V. & Marquis, R. E. ( 1986; ). Acid tolerance, proton permeabilities, and membrane ATPases of oral streptococci. Infect Immun 53, 331–338.
    [Google Scholar]
  5. Biswas, I., Drake, L., Erkina, D. & Biswas, S. ( 2008; ). Involvement of sensor kinases in the stress tolerance response of Streptococcus mutans. J Bacteriol 190, 68–77.[CrossRef]
    [Google Scholar]
  6. Burne, R. A., Quivey, R. G., Jr & Marquis, R. E. ( 1999; ). Physiologic homeostasis and stress responses in oral biofilms. Methods Enzymol 310, 441–460.
    [Google Scholar]
  7. Chaussee, M. S., Somerville, G. A., Reitzer, L. & Musser, J. M. ( 2003; ). Rgg coordinates virulence factor synthesis and metabolism in Streptococcus pyogenes. J Bacteriol 185, 6016–6024.[CrossRef]
    [Google Scholar]
  8. Cotter, P. D. & Hill, C. ( 2003; ). Surviving the acid test: responses of Gram-positive bacteria to low pH. Microbiol Mol Biol Rev 67, 429–453.[CrossRef]
    [Google Scholar]
  9. Dunning, D. W., McCall, L. W., Powell, W. F., Jr, Arscott, W. T., McConocha, E. M., McClurg, C. J., Goodman, S. D. & Spatafora, G. A. ( 2008; ). SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary. Microbiology 154, 1132–1143.[CrossRef]
    [Google Scholar]
  10. Foster, J. W. ( 1995; ). Low pH adaptation and the acid tolerance response of Salmonella typhimurium. Crit Rev Microbiol 21, 215–237.[CrossRef]
    [Google Scholar]
  11. Fozo, E. M., Scott-Anne, K., Koo, H. & Quivery, R. G., Jr ( 2007; ). Role of unsaturated fatty acid biosynthesis in virulence of Streptococcus mutans. Infect Immun 75, 1537–1539.[CrossRef]
    [Google Scholar]
  12. Griswold, A. R., Jameson-Lee, M. & Burne, R. A. ( 2006; ). Regulation and physiologic significance of the agmatine deiminase system of Streptococcus mutans UA159. J Bacteriol 188, 834–841.[CrossRef]
    [Google Scholar]
  13. Hahn, K., Faustoferri, R. C. & Quivey, R. G., Jr ( 1999; ). Induction of an AP endonuclease activity in Streptococcus mutans during growth at low pH. Mol Microbiol 31, 1489–1498.[CrossRef]
    [Google Scholar]
  14. Haldenwang, W. G. ( 1995; ). The sigma factors of Bacillus subtilis. Microbiol Rev 59, 1–30.
    [Google Scholar]
  15. Hamilton, I. R. & Svensäter, G. ( 1998; ). Acid-regulated proteins induced by Streptococcus mutans and other oral bacteria during acid shock. Oral Microbiol Immunol 13, 292–300.[CrossRef]
    [Google Scholar]
  16. 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.[CrossRef]
    [Google Scholar]
  17. Hasona, A., Zuobi-Hasona, K., Crowley, P. J., Abranches, J., Ruelf, M. A., Bleiweis, A. S. & Brady, L. J. ( 2007; ). Membrane composition changes and physiological adaptation by Streptococcus mutans signal recognition particle pathway mutants. J Bacteriol 189, 1219–1230.[CrossRef]
    [Google Scholar]
  18. Helmann, J. D. ( 2002; ). The extracytoplasmic function (ECF) sigma factors. Adv Microb Physiol 46, 47–110.
    [Google Scholar]
  19. Idone, V., Brendtro, S., Gillespie, R., Kocaj, S., Peterson, E., Rendi, M., Warren, W., Michalek, S., Krastel, K. & other authors ( 2003; ). Effect of an orphan response regulator on Streptococcus mutans sucrose-dependent adherence and cariogenesis. Infect Immun 71, 4351–4360.[CrossRef]
    [Google Scholar]
  20. Kakinuma, Y. ( 1998; ). Inorganic cation transport and energy transduction in Enterococcus hirae and other streptococci. Microbiol Mol Biol Rev 62, 1021–1045.
    [Google Scholar]
  21. Kawada-Matsuo, M., Shbata, Y. & Yamashita, Y. ( 2009; ). Role of two component signaling response regulators in acid tolerance of Streptococcus mutans. Oral Microbiol Immunol 24, 173–176.[CrossRef]
    [Google Scholar]
  22. Kreth, J., Hung, D. C. I., Merritt, J., Perry, J., Zhu, L., Goodman, S. D., Cvitkovitch, D. G., Shi, W. & Qi, F. ( 2007; ). The response regulator ComE in Streptococcus mutans functions both as a transcription activator of mutacin production and repressor of CSP biosynthesis. Microbiology 153, 1799–1807.[CrossRef]
    [Google Scholar]
  23. Kuhnert, W. L., Zheng, G., Roberta, C., Faustoferri, R. C. & Quivey, R. G., Jr ( 2004; ). The F-ATPase operon promoter of Streptococcus mutans is transcriptionally regulated in response to external pH. J Bacteriol 186, 8524–8528.[CrossRef]
    [Google Scholar]
  24. Kuramitsu, H. K., He, X., Lux, R., Anderson, M. H. & Shi, W. ( 2007; ). Interspecies interactions within oral microbial communities. Microbiol Mol Biol Rev 71, 653–670.[CrossRef]
    [Google Scholar]
  25. Lau, P. C., Sung, C. K., Lee, J. H., Morrison, D. A. & Cvitkovitch, D. G. ( 2002; ). PCR ligation mutagenesis in transformable streptococci: application and efficiency. J Microbiol Methods 49, 193–205.[CrossRef]
    [Google Scholar]
  26. Lemos, J. A. & Burne, R. A. ( 2008; ). A model of efficiency: stress tolerance by Streptococcus mutans. Microbiology 154, 3247–3255.[CrossRef]
    [Google Scholar]
  27. Lemos, J. A., Abtanches, J. & Burne, R. A. ( 2005; ). Responses of cariogenic streptococci to environmental stresses. Curr Issues Mol Biol 7, 95–108.
    [Google Scholar]
  28. Len, A. C., Harty, D. W. & Jacques, N. A. ( 2004; ). Stress-responsive proteins are upregulated in Streptococcus mutans during acid tolerance. Microbiology 150, 1339–1351.[CrossRef]
    [Google Scholar]
  29. Lévesque, C. M., Mair, R. W., Perry, J. A., Lau, P. C. Y., Li, Y.-H. & Cvitkovitch, D. G. ( 2007; ). Systemic inactivation and phenotypic characterization of two-component systems in expression of Streptococcus mutans virulence properties. Lett Appl Microbiol 45, 398–404.[CrossRef]
    [Google Scholar]
  30. Li, Y.-H., Lau, P. C. Y., Lee, J. H., Ellen, R. P. & Cvitkovitch, D. G. ( 2001a; ). Natural genetic transformation of Streptococcus mutans growing in biofilms. J Bacteriol 183, 897–908.[CrossRef]
    [Google Scholar]
  31. Li, Y.-H., Hanna, M. N., Svensäter, G., Ellen, R. P. & Cvitkovitch, D. G. ( 2001b; ). Cell density modulates acid adaptation in Streptococcus mutans: implication for survival in biofilms. J Bacteriol 183, 6875–6884.[CrossRef]
    [Google Scholar]
  32. Li, Y.-H., Lau, P. C. Y., Tang, N., Svensäter, G., Ellen, R. P. & Cvitkovitch, D. G. ( 2002; ). Novel two-component regulatory system involved in biofilm formation and acid resistance in Streptococcus mutans. J Bacteriol 184, 6333–6342.[CrossRef]
    [Google Scholar]
  33. Li, Y.-H., Tian, X.-L., Layton, G., Norgaard, C. & Sisson, G. ( 2008; ). Additive attenuation of virulence and cariogenic potential of Streptococcus mutans by simultaneous inactivation of the ComCDE quorum sensing system and HK/RR11 two-component regulatory system. Microbiology 154, 3256–3265.[CrossRef]
    [Google Scholar]
  34. Magalhaes, P. P., Paulino, T. P., Thedei, G., Jr & Ciancaglini, P. ( 2005; ). Kinetic characterization of P-type membrane ATPase from Streptococcus mutans. Comp Biochem Physiol B Biochem Mol Biol 140, 589–597.[CrossRef]
    [Google Scholar]
  35. Marsh, P. D. ( 1994; ). Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res 8, 263–271.
    [Google Scholar]
  36. Martin, B., Quentin, Y., Fichant, G. & Claverys, J.-P. ( 2006; ). Independent evolution of competence regulatory cascades in streptococci? Trends Microbiol 14, 339–345.[CrossRef]
    [Google Scholar]
  37. Martin-Galiano, A. J., Ferrandiz, M. J. & de la Campa, A. G. ( 2001; ). The promoter of the operon encoding the F0F1 ATPase of Streptococcus pneumoniae is inducible by pH. Mol Microbiol 41, 1327–1338.[CrossRef]
    [Google Scholar]
  38. Merritt, J., Qi, F. & Shi, W. ( 2005; ). A unique nine-gene comY operon in Streptococcus mutans. Microbiology 151, 157–166.[CrossRef]
    [Google Scholar]
  39. Nascimento, M. M., Lemos, J. A., Abranches, J., Gonçalves, R. B. & Burne, R. A. ( 2004; ). Adaptive acid tolerance response of Streptococcus sobrinus. J Bacteriol 186, 6383–6390.[CrossRef]
    [Google Scholar]
  40. Quivey, R. G., Jr, Kuhnert, W. L. & Hahn, K. ( 2001; ). Genetics of acid adaptation in oral streptococci. Crit Rev Oral Biol Med 12, 301–314.[CrossRef]
    [Google Scholar]
  41. Svensäter, G., Larsson, U. B., Greif, E. C., Cvitkovitch, D. G. & Hamilton, I. R. ( 1997; ). Acid tolerance response and survival by oral bacteria. Oral Microbiol Immunol 12, 266–273.[CrossRef]
    [Google Scholar]
  42. Syvitski, R. T., Tian, X.-L., Sampara, K., Salman, A., Lee, S. F., Jakeman, D. L. & Li, Y.-H. ( 2007; ). Structure–activity analysis of quorum sensing signaling peptides from Streptococcus mutans. J Bacteriol 189, 1441–1450.[CrossRef]
    [Google Scholar]
  43. van der Ploeg, J. R. ( 2005; ). Regulation of bacteriocin production in Streptococcus mutans by the quorum-sensing system required for development of genetic competence. J Bacteriol 187, 3980–3989.[CrossRef]
    [Google Scholar]
  44. Vats, N. & Lee, S. F. ( 2001; ). Characterization of a copper-transport operon, copYAZ, from Streptococcus mutans. Microbiology 147, 653–662.
    [Google Scholar]
  45. Vickerman, M. M. & Minick, P. E. ( 2002; ). Genetic analysis of the rgg-gtfG junctional region and its role in Streptococcus gordonii glucosyltransferase activity. Infect Immun 70, 1703–1714.[CrossRef]
    [Google Scholar]
  46. Wilkins, J. C., Homer, K. A. & Beighton, D. ( 2002; ). Analysis of Streptococcus mutans proteins modulated by culture under acidic conditions. Appl Environ Microbiol 68, 2382–2390.[CrossRef]
    [Google Scholar]
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vol. , part 10, pp. 3322-3332

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Primers used for qRT-PCR and construction of the mutants in this study.

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Genes differentially expressed in during acid adaptation.

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