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

Chapter 7
severely affected in their ability to adhere to human epithelial Detroit 562 cells. These
mutants are also severely reduced in the ability to colonize the murine nasopharynx (17).
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In a recent paper, the transcriptional response of S. pneumoniae upon contact with
human epithelial cells was described (48). In this study, microarray analysis revealed that the
transcriptional activity of many genes is changed when pneumococcal cells interact with
epithelial cells. Interestingly, some pronounced CodY targets were among these genes. For
example, the genes ilvB, ilvE, and asd (encoding acetolactate synthase, branched chain amino
acid aminotransferase, and aspartate semi-aldehyde dehydrogenase, respectively), were
strongly downregulated. This is in agreement with our observations that the codY mutant is
severely affected in its ability to adhere to the Detroit 562 epithelial cells (17). In the codY
mutant, ilvB, ilvE, and asd, were strongly upregulated during in vitro growth. This
upregulation might have had a negative effect on the adherence ability.
Figure 2. Model of transcriptional regulation by CodY (Y) during colonization. During contact with epithelial
cells CodY-regulation is required for the expression of PcpA, a putative adhesin. Expression of other genes in
the CodY-regulon, e.g. aliA and aliB, will be repressed.
The gene pcpA, encoding a choline binding protein, is one of the genes that is directly
regulated by CodY (17). Of note, although CodY usually represses its targets, it appears to
directly activate expression of pcpA, as PcpA was downregulated in the codY mutant and
CodY interacts with the promoter. Interestingly, the pcpA mutant was similarly affected in
adherence as the codY mutant, and no additive phenotype was observed in the pcpA-codY