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

Gene regulation and metabolism in S. pneumoniae
In B. subtilis, glutamine synthetase converts glutamate and ammonium to glutamine.
Its enzymatic activity is directly inhibited by glutamine. In contrast to GlnR, the gene
encoding TnrA is transcribed mono-cistronically. This MerR regulator protein family member
binds to specific DNA recognition sites, which, interestingly, overlap with GlnR recognition
sites. Sonenshein has recently described a model for regulation by GlnR and TnrA in which
the transcriptional regulators TnrA and GlnR, the metabolic enzyme GlnA, and the amino
acid glutamine play key roles (47). In this model, feedback-inhibition of GlnA as a result of
inhibition by glutamine determines the binding capacity of GlnR and TnrA through direct
protein-protein interaction. During nitrogen-limitation, GlnA is enzymatically active, while
TnrA binds to its DNA-binding recognition site. Subsequently, TnrA activates or represses
genes, while GlnR is not able to bind to the DNA because it cannot dimerize. Conversely,
when glutamine is abundantly present, GlnA will be feedback-inhibited as a result of
glutamine binding, resulting in inactivation of its enzymatic activity. GlnA will be able to
interact with TnrA, which when complexed with GlnA is no longer able to bind to its DNA
recognition sequences. In contrast, GlnR in complex with feedback-inhibited GlnA will bind
to DNA, thereby repressing gene expression of its targets (47). Recently, supporting evidence
for this model was provided by Wray and Fisher (54). Their data suggest that the C-terminal
domain of GlnR acts as an auto-inhibitory domain, since truncated versions of GlnR lacking
this domain formed significantly more dimers than the full-length proteins.
The genomes of L. lactis and S. pneumoniae do not contain a homologue of TnrA.
Furthermore, we found that the only target that pneumococcal GlnR shares with B. subtilis
GlnR is the glnRA operon (24 and chapter 5). In B. subtilis, GlnR also regulates the
expression of tnrA and that of the ureABC operon, genes which are not present in S.
pneumoniae (12, 52). Interestingly, the ureABC operon is under strict regulation of GlnR,
TnrA and CodY in B.subtilis, with CodY being the major repressor (52).
The above suggests that nitrogen regulation in lactic acid bacteria varies considerably
from other studied Gram-positive bacteria. For instance, the expression of gdhA is regulated
by both GlnR and CodY in S. pneumoniae (17, 24), while this gene is regulated by CcpA,
RocR, and AhrC in B. subtilis (3). These differences in nitrogen regulation could be a
reflection of the different preferences for particular niches, although the lactic acid bacterial
species can inhabit a wide variety of niches.
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