Gene regulation in Streptococcus pneumoniae - RePub - Erasmus ...

egulatory systems, aiming to elucidate their role both in the context of pneumococcal
physiology, and with respect to pneumococcal virulence.
Introduction
Chapter 2 describes the role of response regulator 09 (RR09) in global gene
expression and in virulence. Strain-dependent features of this regulator were identified by
testing rr09 knock out mutants in strains D39 and TIGR4 in virulence and gene expression
studies. Moreover, expression levels of some of the newly identified differentially expressed
genes were monitored in vivo.
Chapter 3 reports on the manganese-dependent transcriptional regulator PsaR. Using
psaR knock out mutants of two strains (TIGR4 and D39), virulence studies showed strainspecific
phenotypes. Transcriptome and proteome analysis revealed that transcription and
translation of several genes were affected in expression by the psaR mutation, which differed
between the two strains tested.
The nutritional regulator CodY is investigated extensively in Chapter 4. The
identified gene regulatory pathways controlled by CodY are described, as well as the impact
of CodY on virulence. Furthermore, the CodY DNA binding domain was identified, and the
influence of branched chain amino acids and GTP on DNA binding by CodY was examined.
Lastly, the role of pcpA, one of the gene targets, was investigated during adherence.
Chapter 5 and 6 describe the role of glutamine/glutamate metabolism in
pneumococcus. In Chapter 5 the genes regulated by GlnR were identified and studied at the
molecular level. In addition, the DNA-binding sequence of GlnR was identified. In Chapter
6, the role of GlnR and its target genes described in Chapter 5 was extended to virulence in
mice.
In Chapter 7, we provide a comprehensive overview of the role of CodY and GlnR in
metabolic regulation and virulence in pneumococci and other related species, integrating both
existing literature and our own results described in Chapters 4, 5, and 6.
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