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

Chapter 8
for virulence in a serotype 3 strain (11), and we extended these studies using two other strains,
D39 (serotype 2) and TIGR4 (serotype 4). Mutants lacking psaR displayed strain-specific
phenotypes, evident mainly from differences in its contribution to development of bacteremia
in mice. In addition, we also observed genes to be affected in expression in the psaR mutant
in only one of the tested strain backgrounds. Among these strain-specific regulated genes was
the rlrA pathogenicity islet (see above) (27). The psa operon, prtA, and pcpA were confirmed
as PsaR-targets in both D39 and TIGR4 in our study (17, 19), One of these common PsaR
targets, the choline-binding protein PcpA, was demonstrated to be required for adherence to a
human pharyngeal cell line (12, 28). Moreover, regulation of expression of this adherence
factor was shown to be directly positively affected by the nutritional regulator CodY (12 and
chapter 4), while PsaR negatively regulates the expression of pcpA. CodY was shown to bind
to the pcpA promoter regions thereby activating transcription of pcpA (12). This suggests a
direct mechanism for adherence of pneumococcal cells to pharyngeal cells as a reaction on
nutrient availability (chapter 7). These results are underscored by several studies showing
higher expression of psaA and pcpA in in vivo situations (e.g., during contact with
nasopharynx epithelial cells, and in the murine nose, lungs and blood) (20, 21). Contradictory
results were also described: pcpA is not involved in colonization, but in invasive disease (8,
Cron et al., personal communication). In addition, Bootsma et al. found that expression of
pcpA was lower in nasopharyngeal lavage fluid than in culture medium (Bootsma et al.,
personal communication, see also chapter 7). Thus, the exact role of PcpA during
pneumococcal disease remains unclear. The data described above imply that strain-specificity
of pneumococcus may complicate the examination of the cellular processes involved in
virulence. Moreover, it suggests that expression of potential pneumococcal antigens may
occur in a strain-specific manner, similar to the variety of capsular serotypes.
Nitrogen is a vital element for virtually all biological molecules. Therefore, bacteria
have to ensure that they can utilize nitrogen from their continuously changing environment.
Bacteria have developed sophisticated uptake and metabolic systems for the acquisition of
nitrogen-containing molecules. In several Gram-positive bacteria, these systems have been
well studied, but not much was known about the importance of nitrogen regulatory systems
during the pneumococcal life cycle. In chapters 4, 5, and 6 we investigated the two main
regulatory systems controlling nitrogen uptake, metabolism and inter-conversion in S.
pneumonia, CodY and GlnR (12, 14, 18). Since we already extensively described these
regulatory systems in Chapter 7, they will only be discussed briefly here.
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