The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system
Fig 9
Model how Legionella CsrA influences the pyruvate metabolism and which different regulatory functions it exerts.
A) Carbon flux into the energy production is favored by CsrA, whereas production of the storage molecule PHB is repressed. Additionally, amino acids and glucose, but not glycerol are the preferred carbon source in presence of CsrA. Proteins in red represent a negative effect of CsrA on the pathway, whereas in green, proteins are shown to be under positive control of CsrA. In black, CsrA interacts with the RNA, but no quantitive difference was observed under our condition. PrsA (Lpp0607), Ribose-phosphate pyrophosphokinase, RpiA (Lpp0108), Ribose-5-phosphate isomerase A, GlpD (Lpp1368), Glycerol-3-phosphate dehydrogenase, GlpK (Lpp1369), glycerol kinase, Tpi (Lpp2838), Triosephosphate isomerase, Zwf (Lpp0483), Glucose-6-phosphate 1-dehydrogenase, Pgl (Lpp0484), 6-Phosphogluconolactonase, Edd (Lpp0485), 6-Phosphogluconate dehydratase, Gap (Lpp0153), Glyceraldehyde 3-phosphate dehydrogenase, Pgk (Lpp0152), 3-Phosphoglycerate kinase, Eno (Lpp2020), Enolase, Pyk (Lpp0151), Pyruvate kinase, PpsA (Lpp0567), Phosphoenolpyruvate synthase, Pdh (Lpp1461), Pyruvate dehydrogenase complex, Pyc (Lpp0531), Pyruvate carboxyltransferase, Ppc (Lpp1572) Phosphoenolpyruvate carboxylase, SfcA (Lpp3043), NAD-specific malic enzyme, AcnA (LPP1659), Aconitate hydratase, Icd (Lpp0878), Isocitrate dehydrogenase, Sdh (Lpp0595), Succinate dehydrogenase, Suc (Lpp0597), 2-Oxoglutarate dehydrogenase, Ald (Lpp0986), Alanine dehydrogenase, SdaA (Lpp0854), Serine dehydratase, PhbB (Lpp0621), acetoacetyl-CoA reductase, PhbC (Lpp2038), Polyhydroxyalkanoate synthase, Adc (Lpp0728) Acetoacetate decarboxylase, Bdh (Lpp2264), 3-Hydroxybutyrate dehydrogenase. B) CsrA can act as a negative regulator of the translation initiation process by blocking the ribosome binding site of the RNA and hence, interfering with its ribosome interaction. Examples in L. pneumophila are the transcriptional regulator FleQ and the quorum sensing response regulator LqsR. Binding of CsrA leads to a conformational re-organization of the target-RNA. As a consequence, the RBS is better accessible for the ribosome yielding in a translational activation due to CsrA interaction. This mode of action might be relevant for the relA mRNA in L. pneumophila. CsrA interaction with the RNA can stabilize the target-RNA by blocking RNase-specific binding sites. Contrary, also a destabilization can be triggered by CsrA when its binding leads to conformational changes of the RNA that facilitate the attack of an RNase. In Legionella, we suggest that the fur mRNA is protected by CsrA against degradation by binding to an A(N)GGA motif overlapping a putative RNase E recognition site. Finally, CsrA can affect transcriptional elongation in a negative (promoting termination) or in a positive way (stabilizing an anti-terminator structure). The transcription of the gap gene in L. pneumophila is only guaranteed in presence of CsrA as binding of the protein prevents the Rho-dependent termination downstream of the tkt gene part of the PPP/Glycolysis operon.