title: Cross talk between the response regulators PhoB and TctD allows for the integration of diverse environmental signals in Pseudomonas aeruginosa.
abstract: Two-component systems (TCS) serve as stimulus-response coupling mechanisms to allow organisms to adapt to a variety of environmental conditions. The opportunistic pathogen Pseudomonas aeruginosa encodes for more than 100 TCS components. To avoid unwanted cross-talk, signaling cascades are very specific, with one sensor talking to its cognate response regulator (RR). However, cross-regulation may provide means to integrate different environmental stimuli into a harmonized output response. By applying a split luciferase complementation assay, we identified a functional interaction of two RRs of the OmpR/PhoB subfamily, namely PhoB and TctD in P. aeruginosa. Transcriptional profiling, ChIP-seq analysis and a global motif scan uncovered the regulons of the two RRs as well as a quadripartite binding motif in six promoter regions. Phosphate limitation resulted in PhoB-dependent expression of the downstream genes, whereas the presence of TctD counteracted this activation. Thus, the integration of two important environmental signals e.g. phosphate availability and the carbon source are achieved by a titration of the relative amounts of two phosphorylated RRs that inversely regulate a common subset of genes. In conclusion, our results on the PhoB and TctD mediated two-component signal transduction pathways exemplify how P. aeruginosa may exploit cross-regulation to adapt bacterial behavior to complex environments.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bielecki
authors.affiliation: Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Jensen
authors.affiliation: Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Schulze
authors.affiliation: Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Gödeke
authors.affiliation: Department of Molecular Bacteriology; Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Strehmel
authors.affiliation: Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany Department of Molecular Bacteriology; Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Eckweiler
authors.affiliation: Department of Molecular Bacteriology; Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Nicolai
authors.affiliation: Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany Department of Molecular Bacteriology; Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany.
authors.forename: Agata
authors.initials: A
authors.lastname: Bielecka
authors.affiliation: Junior Research Group 3, Robert Koch-Institute, Wernigerode Branch, Burgstrasse 37, 38855 Wernigerode, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wille
authors.affiliation: Junior Research Group 3, Robert Koch-Institute, Wernigerode Branch, Burgstrasse 37, 38855 Wernigerode, Germany.
authors.forename: Roman G
authors.initials: RG
authors.lastname: Gerlach
authors.affiliation: Institute of Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany Department of Molecular Bacteriology; Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany susanne.haeussler@helmholtz-hzi.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism; D018085:Regulon; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C061278:PhoB protein, Bacteria; D008156:Luciferases