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

Introduction
Regulation of gene expression in bacteria is crucial for survival, as specific gene
products are required during specific conditions, and therefore need to be expressed and
regulated accordingly. Especially in bacterial model organisms like Escherichia coli and
Bacillus subtilis, regulators of gene expression have been investigated extensively. Similarly,
various studies have shown that gene regulatory networks control various cellular processes
of the human Gram-positive pathogen Streptococcus pneumoniae, which are essential for
different aspects of pneumococcal pathogenesis. Over the last 10 years, attempts to identify
the actual genes involved in these processes have been made in several large-scale studies
using a signature-tagged mutagenesis approach (4, 16, 27, 36). These studies have
demonstrated the impact of a variety of gene products on the different phases of
pneumococcal infection such as colonization and invasive disease, many of which (are
predicted to) encode transcriptional regulators. Interestingly, several of these regulatory genes
were found to contribute to virulence in a tissue-specific manner. Apart from the known
virulence genes, genes involved in basal metabolism appear to have a vital role in
pneumococcal pathogenesis as well.
Studies on bacterial metabolism and production of secondary metabolites have
elucidated many basal and conserved metabolic pathways, such as glycolysis,
gluconeogenesis, and nitrogen assimilation. Especially for bacteria with industrial relevance,
this knowledge has been used to improve their industrial application, for instance flavor
improvement by the dairy bacterium Lactococcus lactis, or increased yields of solvents
produced by Pseudomonas putida and Clostridium acetobutylicum.
For pathogenic bacteria such as S. pneumoniae, knowledge of metabolic pathways is
still limited. The ability of these bacteria to adapt to specific niches is likely to be reflected in
their metabolic pathways and the regulation thereof. The link between these regulatory
pathways and bacterial virulence is nowadays increasingly recognized.
Gene regulation and metabolism in S. pneumoniae
In this review we discuss regulation of nitrogen acquisition and metabolism in S.
pneumoniae, which is predominantly mediated by GlnR and CodY. These regulatory proteins
have been studied extensively in Bacillus subtilis and Lactococcus lactis, and in several other
Firmicutes. This group also contains pathogenic species for which GlnR and CodY have been
linked directly or indirectly to virulence (31, 35, 45). These studies are discussed in detail,
and, when applicable, put in the context of pneumococcal GlnR and CodY. In addition, the
role of these regulators and their identified targets in pneumococcal virulence are discussed.
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