40. Shivers, R. P., S. S. D<strong>in</strong>een, and A. L. Sonenshe<strong>in</strong>. 2006. Positive <strong>regulation</strong> of Bacillus subtilis ackA by CodY and CcpA: establish<strong>in</strong>g a potential hierarchy <strong>in</strong> carbon flow. Mol. Microbiol. 62:811-22. 41. Shivers, R. P., and A. L. Sonenshe<strong>in</strong>. 2004. Activation of the Bacillus subtilis global regulator CodY by direct <strong>in</strong>teraction with branched-cha<strong>in</strong> am<strong>in</strong>o acids. Mol. Microbiol. 53:599-611. 42. Sonenshe<strong>in</strong>, A. L. 2005. CodY, a global regulator of stationary phase and virulence <strong>in</strong> Gram-positive bacteria. Curr. Op<strong>in</strong>. Microbiol. 8:203-7. 43. Spellerberg, B., D. R. Cundell, J. Sandros, B. J. Pearce, I. Idanpaan-Heikkila, C. Rosenow, and H. R. Masure. 1996. Pyruvate oxidase, as a determ<strong>in</strong>ant of virulence <strong>in</strong> <strong>Streptococcus</strong> <strong>pneumoniae</strong>. Mol. Microbiol. 19:803-13. 44. Ste<strong>in</strong>er, K., and H. Malke. 2000. Life <strong>in</strong> prote<strong>in</strong>-rich environments: the relA- <strong>in</strong>dependent response of <strong>Streptococcus</strong> pyogenes to am<strong>in</strong>o acid starvation. Mol. Microbiol. 38:1004-16. 45. Ste<strong>in</strong>er, K., and H. Malke. 2001. relA-Independent am<strong>in</strong>o acid starvation response network of <strong>Streptococcus</strong> pyogenes. J. Bacteriol. 183:7354-64. The CodY regulon of S. <strong>pneumoniae</strong> 46. Tettel<strong>in</strong>, H., K. E. Nelson, I. T. Paulsen, J. A. Eisen, T. D. Read, S. Peterson, J. Heidelberg, R. T. DeBoy, D. H. Haft, R. J. Dodson, A. S. Durk<strong>in</strong>, M. Gw<strong>in</strong>n, J. F. Kolonay, W. C. Nelson, J. D. Peterson, L. A. Umayam, O. White, S. L. Salzberg, M. R. Lewis, D. Radune, E. Holtzapple, H. Khouri, A. M. Wolf, T. R. Utterback, C. L. Hansen, L. A. McDonald, T. V. Feldblyum, S. Angiuoli, T. Dick<strong>in</strong>son, E. K. Hickey, I. E. Holt, B. J. Loftus, F. Yang, H. O. Smith, J. C. Venter, B. A. Dougherty, D. A. Morrison, S. K. Holl<strong>in</strong>gshead, and C. M. Fraser. 2001. Complete genome sequence of a virulent isolate of <strong>Streptococcus</strong> <strong>pneumoniae</strong>. Science 293:498- 506. 47. Tojo, S., T. Satomura, K. Morisaki, J. Deutscher, K. Hirooka, and Y. Fujita. 2005. Elaborate transcription <strong>regulation</strong> of the Bacillus subtilis ilv-leu operon <strong>in</strong>volved <strong>in</strong> the biosynthesis of branched-cha<strong>in</strong> am<strong>in</strong>o acids through global regulators of CcpA, CodY and TnrA. Mol. Microbiol. 56:1560-73. 48. van Hijum, S. A., A. de Jong, R. J. Baerends, H. A. Karsens, N. E. Kramer, R. Larsen, C. D. den Hengst, C. J. Albers, J. Kok, and O. P. Kuipers. 2005. A generally applicable validation scheme for the assessment of factors <strong>in</strong>volved <strong>in</strong> reproducibility and quality of DNA-microarray data. BMC Genomics 6:77. 119 119
Chapter 4 49. van Hijum, S. A., J. Garcia de la Nava, O. Trelles, J. Kok, and O. P. Kuipers. 2003. MicroPreP: a cDNA microarray data pre-process<strong>in</strong>g framework. Appl. Bio<strong>in</strong>formatics 2:241-4. 120 120
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Gene regulation in Streptococcus pn
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Promotiecommissie Promotoren: Prof.
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CHAPTER 1 Introduction 7
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Introduction Figure 1. Infections c
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Interestingly, autolysis induced by
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histidine kinase is the sensor prot
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metabolism are often required for v
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egulatory systems, aiming to elucid
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11. Cockeran, R., A. J. Theron, H.
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33. Li, S., S. J. Kelly, E. Lamani,
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53. Romero, P., R. Lopez, and E. Ga
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CHAPTER 2 Regulation of gene expres
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Introduction Streptococcus pneumoni
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Materiaals and Meethods Gene regula
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(Invitrogen), 0.2 mM aminoallyl dUT
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Isolation of pneumococcal RNA durin
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Resultss and Discuussion Gene regul
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Table 1. Genes regulated by RR09 in
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phosphofructokinase, and a fructose
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Figure 4. Expression of rlrA and rr
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correlated well with our in vitro m
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Figure 7. Bacterial loads in blood
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Acknowledgments This work was suppo
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10. Ibrahim, Y. M., A. R. Kerr, J.
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genome sequence of a virulent isola
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Gene regulation by RR09 in S. pneum
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Gene regulation by RR09 in S. pneum
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Table S4. Genes up- and downregulat
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Table S6. Genes up- and downregulat
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Chapter 3 Abstract 62 62 Previous s
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Chapter 3 between the wild-type and
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Chapter 3 S. pneumoniae TIGR4 by CS
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GlnR-regulon and pneumococcal virul
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Table 2. Differentially expressed g
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Discussion The ability to adequatel
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The microarray data showed that pre
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Acknowledgments WTH is supported by
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12. Ibrahim, Y. M., A. R. Kerr, J.
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33. Zalieckas, J. M., L. V. Wray, J
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CHAPTER 7 Pneumococcal gene regulat
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Introduction Regulation of gene exp
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Gene regulation and metabolism in S
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makes it possible for the pneumococ
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A CcpA homologue exists in the pneu
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double mutant, suggesting direct re
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References Gene regulation and meta
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23. Kerr, A. R., P. V. Adrian, S. E
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45. Sonenshein, A. L. 2005. CodY, a
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CHAPTER 8 Summarizing discussion 20
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that the observed virulence phenoty
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CodY was found to be required for a
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References Summarizing discussion 1
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Summarizing discussion 21. Orihuela
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Samenvatting en discussie Curriculu
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Samenvatting en discussie kunnen ge
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Bevindingen die dit onderbouwen, we
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Curriculum Vitae Curriculum Vitae W
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Dankwoord Jeetje, dat het dan toch
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oekje en ik kijk uit naar de bijbeh