Cross talk between the response regulators PhoB and TctD allows for the integration of diverse environmental signals inPseudomonas 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.

Unsupervised Extraction of Stable Expression Signatures from Public Compendia with an Ensemble of Neural Networks

“…As expected, PhoA was activated in low phosphate concentrations (Figure 4A). PhoA activity was dependent on PhoB and the PhoB-activating histidine kinase PhoR, consistent with published work (Bielecki et al, 2015). Notably, PhoA activity was evident on King’s A and Peptone (Figure 4B).…”

“…One Node164pos gene encodes PhoB, a transcription factor in the PhoR-PhoB two-component system that responds to low environmental phosphate in P. aeruginosa (Bielecki et al, 2015; Blus-Kadosh et al, 2013; Santos-Beneit, 2015). Further, Node164pos is the signature most enriched for a previously defined PhoB regulon (FDR q-value of 8.1e-29 in hypergeometric test).…”

“…Six of the seven PhoB-regulated genes present in Node108neg are also regulated by TctD, a transcriptional repressor (Bielecki et al, 2015). Node108neg primarily represents genes that are both PhoB-activated and TctD-repressed.…”

The Two-Component System RsrS-RsrR Regulates the Tetrathionate Intermediate Pathway for Thiosulfate Oxidation in Acidithiobacillus caldus

“…The RsrS-RsrR and EnvZ-OmpR like two-component systems share significant homology owing to their evolutionary relationship (Rzhepishevska et al, 2007). The high level of sequence similarity and close homologous relation between some TCSs raises the possibility of undesired cross-talk between a sensor kinase and a non-cognate response regulator (Howell et al, 2003; Siryaporn and Goulian, 2008; Procaccini et al, 2011; Guckes et al, 2013; Bielecki et al, 2015; Nguyen et al, 2015). The transcriptional changes of these genes of TCSs in Δ rsrS and Δ rsrR implied that cross-talk potentially occurs between RsrS-RsrR and other TCSs.…”

Comparative evaluation of rRNA depletion procedures for the improved analysis of bacterial biofilm and mixed pathogen culture transcriptomes

“…The aims of such studies have included identifying antisense and other small regulatory RNAs, determining the targets of regulatory proteins, assessing antibiotic resistance fitness costs, and analyzing the process of biofilm formation that represents a distinct mode of growth enabling the bacterium to colonize and persist within the infected host141516171819. The efficiency of P. aeruginosa rRNA depletion by various methods, however, has not been evaluated.…”